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Sample records for amphiphilic antineoplastic lipid

  1. Replication of simulated prebiotic amphiphile vesicles controlled by experimental lipid physicochemical properties

    International Nuclear Information System (INIS)

    Armstrong, Don L; Zidovetzki, Raphael; Markovitch, Omer; Lancet, Doron

    2011-01-01

    We present a new embodiment of the graded autocatalysis replication domain (GARD) for the growth, replication and evolution of lipid vesicles based on a semi-empirical foundation using experimentally measured kinetic values of selected extant lipid species. Extensive simulations using this formalism elucidated the details of the dependence of the replication and properties of the vesicles on the physicochemical properties and concentrations of the lipids, both in the environment and in the vesicle. As expected, the overall concentration and number of amphiphilic components strongly affect average replication time. Furthermore, variations in acyl chain length and unsaturation of vesicles also influence replication rate, as do the relative concentrations of individual lipid types. Understanding of the dependence of replication rates on physicochemical parameters opens a new direction in the study of prebiotic vesicles and lays the groundwork for future studies involving the competition between lipid vesicles for available amphiphilic monomers

  2. Single-component solid lipid nanocarriers prepared with ultra-long chain amphiphilic lipids

    DEFF Research Database (Denmark)

    Wei, Wei; Lu, Xiaonan; Wang, Zegao

    2017-01-01

    HYPOTHESIS: Synthetic sugar alcohol mono-behenates with high melting points, surface activity and resistance to enzymatic lipolysis, are expected to form stable single-component solid lipid nanocarriers (SC-SLNs). The preparation methods and the polar head group of the molecules should affect the......-probe sonication method had a micelle structure with fenofibrate incorporated into a lipid monolayer. This study provides an insight into the systematic development of novel amphiphilic lipids for solid lipid-based drug delivery system.......HYPOTHESIS: Synthetic sugar alcohol mono-behenates with high melting points, surface activity and resistance to enzymatic lipolysis, are expected to form stable single-component solid lipid nanocarriers (SC-SLNs). The preparation methods and the polar head group of the molecules should affect...... using the lipolysis model. The structure and drug distribution of the nanocarriers were studied using AFM and TEM. FINDINGS: Both the polar head group of the molecules and the preparation methods affect the particle size and size distribution. Nanocarriers prepared with sorbitol mono-behenates showed...

  3. Dehydration-induced redistribution of amphiphilic molecules between cytoplasm and lipids is associated with desiccation tolerance in seeds

    NARCIS (Netherlands)

    Buitink, J.; Leprince, O.; Hoekstra, F.A.

    2000-01-01

    This study establishes a relationship between desiccation tolerance and the transfer of amphiphilic molecules from the cytoplasm into lipids during drying, using electron paramagnetic resonance spectroscopy of amphiphilic spin probes introduced into imbibed radicles of pea (Pisum sativum) and

  4. Spider-web amphiphiles as artificial lipid clusters: design, synthesis, and accommodation of lipid components at the air-water interface.

    Science.gov (United States)

    Ariga, Katsuhiko; Urakawa, Toshihiro; Michiue, Atsuo; Kikuchi, Jun-ichi

    2004-08-03

    As a novel category of two-dimensional lipid clusters, dendrimers having an amphiphilic structure in every unit were synthesized and labeled "spider-web amphiphiles". Amphiphilic units based on a Lys-Lys-Glu tripeptide with hydrophobic tails at the C-terminal and a polar head at the N-terminal are dendrically connected through stepwise peptide coupling. This structural design allowed us to separately introduce the polar head and hydrophobic tails. Accordingly, we demonstrated the synthesis of the spider-web amphiphile series in three combinations: acetyl head/C16 chain, acetyl head/C18 chain, and ammonium head/C16 chain. All the spider-web amphiphiles were synthesized in satisfactory yields, and characterized by 1H NMR, MALDI-TOFMS, GPC, and elemental analyses. Surface pressure (pi)-molecular area (A) isotherms showed the formation of expanded monolayers except for the C18-chain amphiphile at 10 degrees C, for which the molecular area in the condensed phase is consistent with the cross-sectional area assigned for all the alkyl chains. In all the spider-web amphiphiles, the molecular areas at a given pressure in the expanded phase increased in proportion to the number of units, indicating that alkyl chains freely fill the inner space of the dendritic core. The mixing of octadecanoic acid with the spider-web amphiphiles at the air-water interface induced condensation of the molecular area. From the molecular area analysis, the inclusion of the octadecanoic acid bears a stoichiometric characteristic; i.e., the number of captured octadecanoic acids in the spider-web amphiphile roughly agrees with the number of branching points in the spider-web amphiphile.

  5. Discriminating binding and positioning of amphiphiles to lipid bilayers by {sup 1}H NMR

    Energy Technology Data Exchange (ETDEWEB)

    Evanics, F. [Department of Chemistry, University of Toronto, UTM, 3359 Mississauga Rd. North Mississauga, Ont., L5L 1C6 (Canada); Prosser, R.S. [Department of Chemistry, University of Toronto, UTM, 3359 Mississauga Rd. North Mississauga, Ont., L5L 1C6 (Canada)]. E-mail: sprosser@utm.utoronto.ca

    2005-04-04

    The binding and positioning in lipid bilayers of three well-known drugs--imipramine, nicotine, and caffeine--have been studied using {sup 1}H NMR. The membrane model system consisted of 'fast-tumbling' lipid bicelles, in which a bilayered lipid domain, composed of the unsaturated lipid, 1,2-dimyristelaidoyl-sn-glycero-3-phosphocholine (DMLPC) was surrounded by a rim of deuterated detergent-like lipids, consisting of 1,2-dihexanoyl-sn-glycero-3-phosphocholine (DHPC-d22). Binding and immersion depth information was obtained by three experiments. (1) {sup 1}H chemical shift perturbations, upon transfer of the amphiphiles from water to a bicelle mixture, were used to estimate regions of the amphiphiles that interact with the membrane. (2) Water contact to resolvable protons was measured through a Nuclear Overhauser Effect (NOE) between water and resolvable drug and lipid resonances. In the case of both lipids and membrane bound drugs, positive NOEs with large cross-relaxation rates were measured for most resonances originating from the membrane hydrophilic region, while negative NOEs were observed predominantly to resonances in the hydrophobic region of the membrane. (3) {sup 1}H NMR measurements of oxygen-induced (paramagnetic) spin-lattice relaxation rates, which are known to increase with membrane immersion depth, were used to corroborate conclusions based on chemical shift perturbations and water-ligand NOEs.

  6. Lipid nanocarriers (GeluPearl) containing amphiphilic lipid Gelucire 50/13 as a novel stabilizer: fabrication, characterization and evaluation for oral drug delivery

    International Nuclear Information System (INIS)

    Date, Abhijit A; Nagarsenker, Mangal S; Vador, Nimish; Jagtap, Aarti

    2011-01-01

    Purpose. To evaluate the ability of Gelucire 50/13 (an amphiphilic lipid excipient) to act as a stabilizer for lipid nanocarriers such as solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) and to establish the ability of Gelucire 50/13 based lipid nanocarriers to improve oral delivery of hydrophobic drugs using repaglinide (RPG) as a model drug. Methods. The ability of Gelucire 50/13 to nanosize various solid lipids was evaluated. The ability of Gelucire 50/13 to yield NLC was evaluated by using Precirol ATO 5 as a model solid lipid and various liquid lipids (oils). Gelucire 50/13 based NLC (GeluPearl) were evaluated for their ability to improve the efficacy of RPG on oral administration in comparison to RPG tablets. The short term stability of RPG-GeluPearl was evaluated at 25 deg. C/60% RH. Results. Gelucire 50/13 could successfully yield SLN and NLC of various solid lipids, demonstrating its potential to act as a novel stabilizer. DSC studies indicated that Gelucire 50/13 interacts with Precirol ATO 5 and this interaction suppresses polymorphic transitions of both the components. RPG-GeluPearl exhibited significantly higher anti-diabetic activity compared to marketed RPG tablets. RPG-GeluPearl demonstrated good colloidal and chemical stability at the end of 1 month.

  7. Rheological and phase behaviour of amphiphilic lipids

    Directory of Open Access Journals (Sweden)

    Alfaro, M. C.

    2000-04-01

    Full Text Available This chapter reviews the different association structures which are likely to be formed by amphiphilic lipids in the liquid-crystalline state and their corresponding shear flow properties. The structure and rheological behaviour of thermotropic liquid crystals, emphasizing the properties of smectic mesophases, and those of lyotropic liquid crystals such as: nematic, lamellar, diluted lamellar, lamellar dispersions, hexagonal and cubic mesophases are described. The importance of a comprehensive rheological characterisation, including rheo-optical techniques, is pointed out for their practical applications, development of formulations and as a useful technique to assist in the determination of phase diagrams. A historical approach has been used to discuss the evolving field of the rheology and structure identification of liquid crystals formed by amphiphilic lipids and surfactants. Non-Newtonian viscous shear flow, thixotropic and antithixotropic phenomena, linear viscoelastic properties -described by dynamic and creep compliance experiments- and non-linear viscoelastic properties - described by the difference of normal stresses and stress relaxation tests are interpreted on the basis of a microstructure-rheology relationship. The polycrystalline nature of liquid crystals turns out to be rather sensitive to shear due to the change of both size and orientation of the liquid-crystalline monodomains under flow.En este capítulo se realiza una revisión de las distintas estructuras coloidales de asociación que pueden formar los lípidos anfifílicos en estado líquido-cristalino y de sus correspondientes propiedades de flujo en cizalla. Se describe la estructura y comportamiento reológico de cristales líquidos termotrópicos, con énfasis en los de tipo esméctico, fases gel, y cristales líquidos liotrópicos: nemáticos, laminares, laminares diluidos, dispersiones de laminares, hexagonales y cúbicos. Se hace hincapié en la importancia de una

  8. (CryoTransmission Electron Microscopy of Phospholipid Model Membranes Interacting with Amphiphilic and Polyphilic Molecules

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    Annette Meister

    2017-10-01

    Full Text Available Lipid membranes can incorporate amphiphilic or polyphilic molecules leading to specific functionalities and to adaptable properties of the lipid bilayer host. The insertion of guest molecules into membranes frequently induces changes in the shape of the lipid matrix that can be visualized by transmission electron microscopy (TEM techniques. Here, we review the use of stained and vitrified specimens in (cryoTEM to characterize the morphology of amphiphilic and polyphilic molecules upon insertion into phospholipid model membranes. Special emphasis is placed on the impact of novel synthetic amphiphilic and polyphilic bolalipids and polymers on membrane integrity and shape stability.

  9. Amphiphilic building blocks for self-assembly: from amphiphiles to supra-amphiphiles.

    Science.gov (United States)

    Wang, Chao; Wang, Zhiqiang; Zhang, Xi

    2012-04-17

    The process of self-assembly spontaneously creates well-defined structures from various chemical building blocks. Self-assembly can include different levels of complexity: it can be as simple as the dimerization of two small building blocks driven by hydrogen bonding or as complicated as a cell membrane, a remarkable supramolecular architecture created by a bilayer of phospholipids embedded with functional proteins. The study of self-assembly in simple systems provides a fundamental understanding of the driving forces and cooperativity behind these processes. Once the rules are understood, these guidelines can facilitate the research of highly complex self-assembly processes. Among the various components for self-assembly, an amphiphilic molecule, which contains both hydrophilic and hydrophobic parts, forms one of the most powerful building blocks. When amphiphiles are dispersed in water, the hydrophilic component of the amphiphile preferentially interacts with the aqueous phase while the hydrophobic portion tends to reside in the air or in the nonpolar solvent. Therefore, the amphiphiles aggregate to form different molecular assemblies based on the repelling and coordinating forces between the hydrophilic and hydrophobic parts of the component molecules and the surrounding medium. In contrast to conventional amphiphiles, supra-amphiphiles are constructed on the basis of noncovalent interactions or dynamic covalent bonds. In supra-amphiphiles, the functional groups can be attached to the amphiphiles by noncovalent synthesis, greatly speeding their construction. The building blocks for supra-amphiphiles can be either small organic molecules or polymers. Advances in the development of supra-amphiphiles will not only enrich the family of conventional amphiphiles that are based on covalent bonds but will also provide a new kind of building block for the preparation of complex self-assemblies. When polymers are used to construct supra-amphiphiles, the resulting

  10. Tumor targeting using liposomal antineoplastic drugs

    Directory of Open Access Journals (Sweden)

    Jörg Huwyler

    2008-03-01

    Full Text Available Jörg Huwyler1, Jürgen Drewe2, Stephan Krähenbühl21University of Applied Sciences Northwestern Switzerland, Institute of Pharma Technology, Muttenz, Switzerland; 2Department of Research and Division of Clinical Pharmacology, University Hospital Basel, Basel, SwitzerlandAbstract: During the last years, liposomes (microparticulate phospholipid vesicles have beenused with growing success as pharmaceutical carriers for antineoplastic drugs. Fields of application include lipid-based formulations to enhance the solubility of poorly soluble antitumordrugs, the use of pegylated liposomes for passive targeting of solid tumors as well as vector-conjugated liposomal carriers for active targeting of tumor tissue. Such formulation and drug targeting strategies enhance the effectiveness of anticancer chemotherapy and reduce at the same time the risk of toxic side-effects. The present article reviews the principles of different liposomal technologies and discusses current trends in this field of research.Keywords: tumor targeting, antineoplastic drugs, liposomes, pegylation, steric stabilization, immunoliposomes

  11. Amphiphilic lipid derivatives of 3'-hydroxyurea-deoxythymidine: preparation, properties, molecular self-assembly, simulation and in vitro anticancer activity.

    Science.gov (United States)

    Li, Miao; Qi, Shuo; Jin, Yiguang; Yao, Weishang; Zhang, Sa; Zhao, Jingyu

    2014-11-01

    Lipid derivatives of nucleoside analogs and their nanoassemblies have become the research hotspot due to their unique function in cancer therapy. Six lipid derivatives of 3'-hydroxyurea-deoxythymidine were prepared with zidovudine as the raw material. The 5'-substituted lipid chains in the derivatives were from the various fatty acids including octanoic acid, decanoic acid, dodecanoic acid, tetradecanoic acid, hexadecanoic acid and octadecanoic acid corresponding to the derivatives OHT, DHT, DDHT, TDHT, HDHT and ODHT. The amphiphilic derivatives formed Langmuir monolayers at the air/water interface with different surface pressure-molecular area isotherms depending on the length of lipid chains. The nanoassemblies of OHT, DHT, DDHT, TDHT and HDHT and the nanoscale precipitates of ODHT were obtained after we injected their tetrahydrofuran solutions doped with hydrophilic long chained polymers into water. Electron microscopy showed that the morphology of nanoassemblies may be vesicles or nanotubes depending on the length of lipid chains. The shorter the lipid chains were, the softer the nanoassemblies. Computer simulation supported the experimental results. The nanoassemblies and the nanoscale precipitates showed much higher anticancer effects on SW620 cells than the parent drug hydroxyurea. The nanostructures of the derivatives are promising anticancer nanomedicines. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Amphiphilic cyclodextrin nanoparticles.

    Science.gov (United States)

    Varan, Gamze; Varan, Cem; Erdoğar, Nazlı; Hıncal, A Atilla; Bilensoy, Erem

    2017-10-15

    Cyclodextrins are cyclic oligosaccharides obtained by enzymatic digestion of starch. The α-, β- and γ- cyclodextrins contain respectively 6, 7 and 8 glucopyranose units, with primary and secondary hydroxyl groups located on the narrow and wider rims of a truncated cone shape structure. Such structure is that of a hydrophobic inner cavity with a hydrophilic outer surface allowing to interact with a wide range of molecules like ions, protein and oligonucleotides to form inclusion complexes. Many cyclodextrin applications in the pharmaceutical area have been widely described in the literature due to their low toxicity and low immunogenicity. The most important is to increase the solubility of hydrophobic drugs in water. Chemically modified cyclodextrin derivatives have been synthesized to enhance their properties and more specifically their pharmacological activity. Among these, amphiphilic derivatives were designed to build organized molecular structures, through selfassembling systems or by incorporation in lipid membranes, expected to improve the vectorization in the organism of the drug-containing cyclodextrin cavities. These derivatives can form a variety of supramolecular structures such as micelles, vesicles and nanoparticles. The purpose of this review is to summarize applications of amphiphilic cyclodextrins in different areas of drug delivery, particularly in protein and peptide drug delivery and gene delivery. The article highlights important amphiphilic cyclodextrin applications in the design of novel delivery systems like nanoparticles. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. How To Tackle the Issues in Free Energy Simulations of Long Amphiphiles Interacting with Lipid Membranes: Convergence and Local Membrane Deformations

    DEFF Research Database (Denmark)

    Filipe, H. A. L.; Moreno, M. J.; Rog, T.

    2014-01-01

    One of the great challenges in membrane biophysics is to find a means to foster the transport of drugs across complex membrane structures. In this spirit, we elucidate methodological challenges associated with free energy computations of complex chainlike molecules across lipid membranes....... As an appropriate standard molecule to this end, we consider 7-nitrobenz-2-oxa-1,3-diazol-4-yl-labeled fatty amine, NBD-C-n, which is here dealt with as a homologous series with varying chain lengths. We found the membrane-water interface region to be highly sensitive to details in free energy computations. Despite...... of radius 1.7 nm from the amphiphile. Importantly, the free energy results given by PGC were found to be qualitatively consistent with experimental data, while the PGD results were not. We conclude that with long amphiphiles there is reason for concern with regard to computations of their free energy...

  14. Molecular dynamics simulations of membrane deformation induced by amphiphilic helices of Epsin, Sar1p, and Arf1

    Science.gov (United States)

    Li, Zhen-Lu

    2018-03-01

    The N-terminal amphiphilic helices of proteins Epsin, Sar1p, and Arf1 play a critical role in initiating membrane deformation. The interactions of these amphiphilic helices with the lipid membranes are investigated in this study by combining the all-atom and coarse-grained simulations. In the all-atom simulations, the amphiphilic helices of Epsin and Sar1p are found to have a shallower insertion depth into the membrane than the amphiphilic helix of Arf1, but remarkably, the amphiphilic helices of Epsin and Sar1p induce higher asymmetry in the lipid packing between the two monolayers of the membrane. The insertion depth of amphiphilic helix into the membrane is determined not only by the overall hydrophobicity but also by the specific distributions of polar and non-polar residues along the helix. To directly compare their ability to deform the membrane, the coarse-grained simulations are performed to investigate the membrane deformation under the insertion of multiple helices. Project supported by the National Natural Science Foundation of China (Grant Nos. 91427302 and 11474155).

  15. Dissolving Microneedle Arrays for Transdermal Delivery of Amphiphilic Vaccines.

    Science.gov (United States)

    An, Myunggi; Liu, Haipeng

    2017-07-01

    Amphiphilic vaccine based on lipid-polymer conjugates is a new type of vaccine capable of self-delivering to the immune system. When injected subcutaneously, amphiphilic vaccines efficiently target antigen presenting cells in the lymph nodes (LNs) via a unique albumin-mediated transport and uptake mechanism and induce potent humoral and cellular immune responses. However, whether this new type of vaccine can be administrated via a safe, convenient microneedle-based transdermal approach remains unstudied. For such skin barrier-disruption systems, a simple application of microneedle arrays (MNs) is desired to disrupt the stratum corneum, and for rapid and pain-free self-administration of vaccines into the skin, the anatomic place permeates with an intricate mesh of lymphatic vessels draining to LNs. Here the microneedle transdermal approach is combined with amphiphilic vaccines to create a simple delivery approach which efficiently traffic molecular vaccines into lymphatics and draining LNs. The rapid release of amphiphilic vaccines into epidermis upon application of dissolving MNs to the skin of mice generates potent cellular and humoral responses, comparable or superior to those elicited by traditional needle-based immunizations. The results suggest that the amphiphilic vaccines delivered by dissolving MNs can provide a simple and safer vaccination method with enhanced vaccine efficacy. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Antineoplastic Drugs

    Science.gov (United States)

    Sadée, Wolfgang; El Sayed, Yousry Mahmoud

    The limited scope of therapeutic drug-level monitoring in cancer chemotherapy results from the often complex biochemical mechanisms that contribute to antineoplastic activity and obscure the relationships among drug serum levels and therapeutic benefits. Moreover, new agents for cancer chemotherapy are being introduced at a more rapid rate than for the treatment of other diseases, although the successful application of therapeutic drug-level monitoring may require several years of intensive study of the significance of serum drug levels. However, drug level monitoring can be of considerable value during phase I clinical trials of new antineoplastic agents in order to assess drug metabolism, bioavailability, and intersubject variability; these are important parameters in the interpretation of clinical studies, but have no immediate benefit to the patient. High performance liquid chromatography (HPLC) probably represents the most versatile and easily adaptable analytical technique for drug metabolite screening (1). HPLC may therefore now be the method of choice during phase I clinical trials of antineoplastic drugs. For example, within a single week we developed an HPLC assay—using a C18 reverse-phase column, UV detection, and direct serum injection after protein precipitation—for the new radiosensitizer, misonidazole (2).

  17. Lipids, lipid bilayers and vesicles as seen by neutrons

    International Nuclear Information System (INIS)

    Seto, Hideki

    2011-01-01

    Lipid molecules self-assemble into bilayers in water with their hydrocarbon chains facing inward due to their amphiphilic nature. The structural and dynamical properties of lipids and lipid bilayers have been studied by neutron scattering intensively. In this article, 3 topics are shown as typical examples. 1) a time-resolved small-angle neutron scattering on uni-lamellar vesicles composed of deuterated and protonated lipids to determine lipid kinetics, 2) small-angle neutron scattering to investigate spontaneous formation of nanopores on uni-lamellar vesicles, and 3) neutron spin echo study to determine bending modulus of lipid bilayers. (author)

  18. Flavonoids from Heliotropium subulatum exudate and their evaluation for antioxidant, antineoplastic and cytotoxic activities II.

    Science.gov (United States)

    Singh, Bharat; Sahu, Pooran M; Sharma, Ram A

    2017-02-01

    The flavonoids are the largest group of phenolic compounds isolated from a wide range of higher plants. These compounds work as antimicrobials, anti-insect agents and protect plants from other types of biotic and abiotic stresses. Various researchers have suggested that flavonoids possessed antioxidant, antineoplastic and cytotoxic activities. The main objective of this study was to test dichloromethane fraction of resinous exudate of Heliotropium subulatum for their antioxidant, antineoplastic and cytotoxic activities, as well as to search new antioxidant and antineoplastic agents for pharmaceutical formulations. Five flavonoids were isolated from resinous exudate of this plant species and screened for their in vitro and in vivo antioxidant models (DPPH radical scavenging, reducing power, superoxide anion scavenging, metal chelating scavenging systems, catalase and lipid peroxidation), antineoplastic (Sarcoma 180), and cytotoxic (Chinese hamster V79 cells) activities. Tricetin demonstrated maximum antioxidant activity against both in vitro and in vivo experimental systems while galangin exhibited maximum inhibition (78.35%) at a dose of 10 µg/kg/day against Sarcoma 180. Similarly, it was found that galangin also showed highest activity (21.1 ± 0.15%) at a concentration of 70 µg/ml to Chinese hamster V79 cells. The observed results suggest that tricetin has a potential to scavenge free radicals in both in vitro and in vivo models while the galangin could be considered as antitumor and cytotoxic agent.

  19. Relation between structure and organisation properties of new amphiphilic cyclodextrins

    International Nuclear Information System (INIS)

    Moutard, Stephane

    2003-01-01

    Since a number of years, special attention and efforts have been made to prepare amphiphilic cyclodextrins (CDs) with the objective to use them to obtain supramolecular assemblies as such or in the presence of preformed lipidic structures. The aim of these investigation is in both cases to combine the size specificity of cyclodextrins for guests and the transport properties of phospho-lipidic structures. The final objects could be of importance to transport or target biologically relevant molecules such as drugs using new galenic formulations. In a first step, a new family of amphiphilic CDs was prepared from a pure phospholipids (DMPE) onto cyclodextrins or methylated derivatives through a spacing arm. The afforded compounds (phospholipidyl-cyclodextrins) were fully characterized by high field NMR and high resolution mass spectrometry. The methylated derivatives were shown to self-organize in water with low CMC to form fluctuating micellar fibers retaining the inclusion capacity of the cyclodextrin cavities. The interactions of these compounds with membrane systems were investigated as black films using X-ray reflectivity and by evaluation of their detergent power towards model DMPC liposomes. Their ability to cross over the Blood Brain Barrier was evidenced by a new approach making use of novel immuno-enzymatic assays. In a second step, a new class of amphiphilic cyclodextrins was considered (peptidolipidyl-cyclodextrins). Although they are structurally similar to phospholipidyl-CDs, their preparation overcomes the tedious steps of the later and lead to a considerable versatility in terms of the number of possible molecules to be prepared. Moreover, the stability problems encountered with phospholipids are avoided. Several examples have been prepared, fully characterized and their organization properties investigated by the determination of CMC and by deuterium NMR on a pure and homogeneous mixed peptidolipidyl-CD / DMPC lamellar phase. This novel class of

  20. Occupational rhinosinusitis due to etoposide, an antineoplastic agent

    DEFF Research Database (Denmark)

    Meyer, Harald W; Skov, Per Stahl

    2010-01-01

    This paper reports a rare case of an occupational hypersensitivity reaction to an antineoplastic agent.......This paper reports a rare case of an occupational hypersensitivity reaction to an antineoplastic agent....

  1. Amphiphile-induced heart muscle-cell (myocyte) injury: effects of intracellular fatty acid overload.

    Science.gov (United States)

    Janero, D R; Burghardt, C; Feldman, D

    1988-10-01

    Lipid amphiphile toxicity may be an important contributor to myocardial injury, especially during ischemia/reperfusion. In order to investigate directly the potential biochemical and metabolic effects of amphiphile overload on the functioning heart muscle cell (myocyte), a novel model of nonesterified fatty acid (NEFA)-induced myocyte damage has been defined. The model uses intact, beating neonatal rat myocytes in primary monolayer culture as a study object and 5-(tetradecyloxy)-2-furoic acid (TOFA) as a nonmetabolizable fatty acid. Myocytes incubated with TOFA accumulated it as NEFA, and the consequent NEFA amphiphile overload elicited a variety of cellular defects (including decreased beating rate, depletion of high-energy stores and glycogen pools, and breakdown of myocyte membrane phospholipid) and culminated in cell death. The amphiphile-induced cellular pathology could be reversed by removing TOFA from the culture medium, which resulted in intracellular TOFA "wash-out." Although the development and severity of amphiphile-induced myocyte injury could be correlated with both the intracellular TOFA/NEFA content (i.e., the level of TOFA to which the cells were exposed) and the duration of this exposure, removal of amphiphile overload did not inevitably lead to myocyte recovery. TOFA had adverse effects on myocyte mitochondrial function in situ (decoupling of oxidative phosphorylation, impairing respiratory control) and on myocyte oxidative catabolism (transiently increasing fatty acid beta oxidation, citric acid cycle flux, and glucose oxidation). The amphiphile-induced bioenergetic abnormalities appeared to constitute a state of "metabolic anoxia" underlying the progression of myocyte injury to cell death. This anoxic state could be ameliorated to some extent, but not prevented, by carbohydrate catabolism.

  2. Omega-3 PUFA Loaded in Resveratrol-Based Solid Lipid Nanoparticles: Physicochemical Properties and Antineoplastic Activities in Human Colorectal Cancer Cells In Vitro

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    Simona Serini

    2018-02-01

    Full Text Available New strategies are being investigated to ameliorate the efficacy and reduce the toxicity of the drugs currently used in colorectal cancer (CRC, one of the most common malignancies in the Western world. Data have been accumulated demonstrating that the antineoplastic therapies with either conventional or single-targeted drugs could take advantage from a combined treatment with omega-3 polyunsaturated fatty acids (omega-3 PUFA. These nutrients, shown to be safe at the dosage generally used in human trials, are able to modulate molecules involved in colon cancer cell growth and survival. They have also the potential to act against inflammation, which plays a critical role in CRC development, and to increase the anti-cancer immune response. In the present study, omega-3 PUFA were encapsulated in solid lipid nanoparticles (SLN having a lipid matrix containing resveratrol esterified to stearic acid. Our aim was to increase the efficiency of the incorporation of these fatty acids into the cells and prevent their peroxidation and degradation. The Resveratrol-based SLN were characterized and investigated for their antioxidant activity. It was observed that the encapsulation of omega-3 PUFA into the SLN enhanced significantly their incorporation in human HT-29 CRC cells in vitro, and their growth inhibitory effects in these cancer cells, mainly by reducing cell proliferation.

  3. Exposure to antineoplastic drugs outside the hospital environment.

    Science.gov (United States)

    Meijster, T; Fransman, W; Veldhof, R; Kromhout, H

    2006-10-01

    The objectives were (i) to identify occupational populations outside hospitals working with antineoplastic drugs, (ii) to determine the size of the populations 'at risk', (iii) to identify major determinants and routes of exposure outside hospitals and (iv) to estimate exposure levels and frequencies relative to levels found in hospitals. The survey consisted of two phases; (i) identification of activities with potential exposure to antineoplastic drugs by literature review, interviews, questionnaires and workplace visits, (ii) exploratory measurements of exposure and surface contamination in selected sectors. Eight sectors were identified with potential exposure to antineoplastic drugs: pharmaceutical industry, pharmacies, universities, veterinary medicine, nursing homes, home care, laundry facilities, and waste treatment. Four sectors were of primary concern: veterinary medicine, home care, nursing homes and industrial laundries. The populations potentially exposed in these sectors vary considerably (from several tens to thousands of workers), as do their levels of exposure. Exposure measurements collected in the veterinary medicine sector showed that workers are indeed exposed to antineoplastic drugs and, in some cases (on gloves after administration), levels were 15 times higher than levels measured during administration in hospitals. Workers sorting contaminated hospital laundry in industrial laundry facilities were exposed to antineoplastic drugs through inhalation. For the home care and nursing homes sectors the highest exposure levels were found when cleaning toilets and washing treated patients. These two sectors are expected to have the largest exposed population (5,000-10,000 individuals). This study has resulted in a comprehensive overview of populations with potential exposure to antineoplastic drugs. Exposure levels can potentially be high compared with the hospital environment, because exposure routes are complex and awareness of the hazard (and

  4. Antifungal amphiphilic aminoglycoside K20: bioactivities and mechanism of action

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    Sanjib K. Shrestha

    2014-12-01

    Full Text Available K20 is a novel amphiphilic antifungal aminoglycoside that is synthetically derived from the antibiotic kanamycin A. Reported here are investigations of K20’s antimicrobial activities, cytotoxicity, and fungicidal mechanism of action. In vitro growth inhibitory activities against a variety of human and plant pathogenic yeasts, filamentous fungi, and bacteria were determined using microbroth dilution assays and time-kill curve analyses, and hemolytic and animal cell cytotoxic activities were determined. Effects on Cryptococcus neoformans H-99 infectivity were determined with a preventive murine lung infection model. The antifungal mechanism of action was studied using intact fungal cells, yeast lipid mutants, and small unilamellar lipid vesicles. K20 exhibited broad-spectrum in vitro antifungal activities but not antibacterial activities. Pulmonary, single dose-administration of K20 reduced C. neoformans lung infection rates 4-fold compared to controls. Hemolysis and half-maximal cytotoxicities of mammalian cells occurred at concentrations that were 10 to 32-fold higher than fungicidal MICs. With fluorescein isothiocyanate, 20 to 25 mg/L K20 caused staining of >95% of C. neoformans and Fusarium graminearum cells and at 31.3 mg/L caused rapid leakage (30 to 80% in 15 min of calcein from preloaded small unilamellar lipid vesicles. K20 appears to be a broad-spectrum fungicide, capable of reducing the infectivity of C. neoformans, and exhibits low hemolytic activity and mammalian cell toxicity. It perturbs the plasma membrane by mechanisms that are lipid modulated. K20 is a novel amphiphilic aminoglycoside amenable to scalable production and a potential lead antifungal for therapeutic and crop protection applications.

  5. Exogenous ether lipids predominantly target mitochondria.

    Directory of Open Access Journals (Sweden)

    Lars Kuerschner

    Full Text Available Ether lipids are ubiquitous constituents of cellular membranes with no discrete cell biological function assigned yet. Using fluorescent polyene-ether lipids we analyzed their intracellular distribution in living cells by microscopy. Mitochondria and the endoplasmic reticulum accumulated high amounts of ether-phosphatidylcholine and ether-phosphatidylethanolamine. Both lipids were specifically labeled using the corresponding lyso-ether lipids, which we established as supreme precursors for lipid tagging. Polyfosine, a fluorescent analogue of the anti-neoplastic ether lipid edelfosine, accumulated to mitochondria and induced morphological changes and cellular apoptosis. These data indicate that edelfosine could exert its pro-apoptotic power by targeting and damaging mitochondria and thereby inducing cellular apoptosis. In general, this study implies an important role of mitochondria in ether lipid metabolism and intracellular ether lipid trafficking.

  6. Synthesis and Application of a New Amphiphilic Antioxidant.

    Science.gov (United States)

    Soliman, Hanaa M; Arafat, Shaker M; Basuny, Amany M; Shattory, Y El-

    2017-11-01

    A new amphiphilic antioxidant (tannyl stearate) derived from reaction of tannic acid with stearic acid was synthesized in order to improve tannic acid solubility in lipid materials. This reaction gives many products having different degree of esterification (tannyl mono, di, tri, tetra, penta, hexa, hepta……stearate) which were separated using silica gel column chromatography and tentative identification was carried out using thin layer chromatography (TLC). The intrinsic viscosities (η) were used to differentiate between the different molecular weight of the produced esters 1) . Tannyl penta stearate is assumed to be the most suitable amphiphilic antioxidant derivative, where those derivatives with less degree of esterification would be less soluble in fat, and those of higher degree of esterification would exhaust more hydroxyl group that cause decreases of antioxidant activity. The structure of tannyl penta stearate was approved depending on its chemical analysis and spectral data (IR, H 1 NMR,). The emulsification power of tannyl penta stearate was then determined according to method described by El-Sukkary et al. 2) , in order to prove its amphiphilic property. Then tannyl penta stearate was tested for its antioxidant and radical scavenging activities in three different manners, those are, lipid oxidation in sunflower oil using Rancimat, (DPPH) free radical scavenging and total antioxidant activity. {Pure tannic acid (T), butylhydroxyanisol (BHA) and butylhydroxytoluene (BHT) were used as reference antioxidant radical saving compounds}. Then tannyl penta stearate was added to sunflower oil, frying process was carried out and all physicochemical parameters of the oil were considered, and compared to other reference antioxidant in order to study the effect of this new antioxidant toward oil stability. Acute oral toxicity of the tannyl penta stearate was carried out using albino mice of 21-25 g body weight to determine its safety according to the method

  7. An Amylase-Responsive Bolaform Supra-Amphiphile.

    Science.gov (United States)

    Kang, Yuetong; Cai, Zhengguo; Tang, Xiaoyan; Liu, Kai; Wang, Guangtong; Zhang, Xi

    2016-02-01

    An amylase-responsive bolaform supra-amphiphile was constructed by the complexation between β-cyclodextrin and a bolaform covalent amphiphile on the basis of host-guest interaction. The bolaform covalent amphiphile could self-assemble in solution, forming sheet-like aggregates and displaying weak fluorescence because of aggregation-induced quenching. The addition of β-cyclodextrin led to the formation of the bolaform supra-amphiphile, prohibiting the aggregation of the bolaform covalent amphiphile and accompanying with the significant recovery of fluorescence. Upon the addition of α-amylase, with the degradation β-cyclodextrin, the fluorescence of the supra-amphiphile would quench gradually and significantly, and the quenching rate linearly correlated to the concentration of α-amylase. This study enriches the field of supra-amphiphiles on the basis of noncovalent interactions, and moreover, it may provide a facile way to estimate the activity of α-amylase.

  8. Functional self-assembled lipidic systems derived from renewable resources.

    Science.gov (United States)

    Silverman, Julian R; Samateh, Malick; John, George

    2016-01-01

    Self-assembled lipidic amphiphile systems can create a variety of multi-functional soft materials with value-added properties. When employing natural reagents and following biocatalytic syntheses, self-assembling monomers may be inherently designed for degradation, making them potential alternatives to conventional and persistent polymers. By using non-covalent forces, self-assembled amphiphiles can form nanotubes, fibers, and other stimuli responsive architectures prime for further applied research and incorporation into commercial products. By viewing these lipid derivatives under a lens of green principles, there is the hope that in developing a structure-function relationship and functional smart materials that research may remain safe, economic, and efficient.

  9. Cellular uptake mechanism and comparative evaluation of antineoplastic effects of paclitaxel–cholesterol lipid emulsion on triple-negative and non-triple-negative breast cancer cell lines

    Directory of Open Access Journals (Sweden)

    Ye J

    2016-08-01

    Full Text Available Jun Ye,1,2 Xuejun Xia,1,2 Wujun Dong,1,2 Huazhen Hao,1,2 Luhua Meng,1,2 Yanfang Yang,1,2 Renyun Wang,1,2 Yuanfeng Lyu,3 Yuling Liu1,2 1State Key Laboratory of Bioactive Substance and Function of Natural Medicines, 2Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 3School of Pharmacy, China Pharmaceutical University, Nanjing, People’s Republic of China Abstract: There is no effective clinical therapy for triple-negative breast cancers (TNBCs, which have high low-density lipoprotein (LDL requirements and express relatively high levels of LDL receptors (LDLRs on their membranes. In our previous study, a novel lipid emulsion based on a paclitaxel–cholesterol complex (PTX-CH Emul was developed, which exhibited improved safety and efficacy for the treatment of TNBC. To date, however, the cellular uptake mechanism and intracellular trafficking of PTX-CH Emul have not been investigated. In order to offer powerful proof for the therapeutic effects of PTX-CH Emul, we systematically studied the cellular uptake mechanism and intracellular trafficking of PTX-CH Emul and made a comparative evaluation of antineoplastic effects on TNBC (MDA-MB-231 and non-TNBC (MCF7 cell lines through in vitro and in vivo experiments. The in vitro antineoplastic effects and in vivo tumor-targeting efficiency of PTX-CH Emul were significantly more enhanced in MDA-MB-231-based models than those in MCF7-based models, which was associated with the more abundant expression profile of LDLR in MDA-MB-231 cells. The results of the cellular uptake mechanism indicated that PTX-CH Emul was internalized into breast cancer cells through the LDLR-mediated internalization pathway via clathrin-coated pits, localized in lysosomes, and then released into the cytoplasm, which was consistent with the internalization pathway and intracellular trafficking of native

  10. Glycaemic adverse drug reactions from anti-neoplastics used in ...

    African Journals Online (AJOL)

    235625 records ... Glycaemic adverse drug reactions from anti-neoplastics used in treating pancreatic cancer. ... Based on the emphasized nine antineoplastic drugs with high hyperglycemic ADR incidence, we found: fluorouracil, sorafenib and pemetrexed with high ADR record of metabolism and nutrition disorders; ...

  11. In situ SERS detection of emulsifiers at lipid interfaces using label-free amphiphilic gold nanoparticles.

    Science.gov (United States)

    Li, Yue; Driver, Michael; Winuprasith, Thunnalin; Zheng, Jinkai; McClements, David Julian; He, Lili

    2014-10-21

    Herein, we fabricated amphiphilic gold nanoparticles (GNPs) that can self-assemble at oil-water interfaces. We applied those GNPs for in situ SERS detection of emulsifier molecules within the interfacial region of oil in water (O/W) emulsion systems.

  12. Positron annihilation lifetime spectroscopy (PALS) as a characterization technique for nanostructured self-assembled amphiphile systems.

    Science.gov (United States)

    Dong, Aurelia W; Pascual-Izarra, Carlos; Pas, Steven J; Hill, Anita J; Boyd, Ben J; Drummond, Calum J

    2009-01-08

    Positron annihilation lifetime spectroscopy (PALS) has potential as a novel rapid characterization method for self-assembly amphiphile systems; however, a lack of systematic correlation of PALS parameters with structural attributes has limited its more widespread application. In this study, using the well-characterized phytantriol/water and the phytantriol/vitamin E acetate/water self-assembly amphiphile systems, the impact of systematic structural changes controlled by changes in composition and temperature on PALS parameters has been studied. The PALS parameters (orthopositronium (oPs) lifetime and intensity signatures) were shown to be sensitive to the molecular packing and mobility of the self-assembled lipid molecules in various lyotropic liquid crystalline phases, enabling differentiation between liquid crystalline structures. The oPs lifetime, related to the molecular packing and mobility, is correlated with rheological properties of the individual mesophases. The oPs lifetime links the lipid chain packing and mobility in the various mesophases to resultant macroscopic properties, such as permeability, which is critical for the use of these mesophase structures as diffusion-controlled release matrices for active liposoluble compounds.

  13. RGD-modified lipid disks as drug carriers for tumor targeted drug delivery

    Science.gov (United States)

    Gao, Jie; Xie, Cao; Zhang, Mingfei; Wei, Xiaoli; Yan, Zhiqiang; Ren, Yachao; Ying, Man; Lu, Weiyue

    2016-03-01

    Melittin, the major component of the European bee venom, is a potential anticancer candidate due to its lytic properties. However, in vivo applications of melittin are limited due to its main side effect, hemolysis, especially when applied through intravenous administration. The polyethylene glycol-stabilized lipid disk is a novel type of nanocarrier, and the rim of lipid disks has a high affinity to amphiphilic peptides. In our study, a c(RGDyK) modified lipid disk was developed as a tumor targeted drug delivery system for melittin. Cryo-TEM was used to confirm the shape and size of lipid disks with or without c(RGDyK) modification. In vitro and in vivo hemolysis analyses revealed that the hemolysis effect significantly decreased after melittin associated with lipid disks. Importantly, the results of our in vivo biodistribution and tumor growth inhibitory experiments showed that c(RGDyK) modification increased the distribution of lipid disks in the tumor and the anticancer efficacy of melittin loaded lipid disks. Thus, we successfully achieved a targeted drug delivery system for melittin and other amphiphilic peptides with a good therapeutic effect and low side effects.

  14. Lipid Nanotechnology

    Directory of Open Access Journals (Sweden)

    Gijsje Koenderink

    2013-02-01

    Full Text Available Nanotechnology is a multidisciplinary field that covers a vast and diverse array of devices and machines derived from engineering, physics, materials science, chemistry and biology. These devices have found applications in biomedical sciences, such as targeted drug delivery, bio-imaging, sensing and diagnosis of pathologies at early stages. In these applications, nano-devices typically interface with the plasma membrane of cells. On the other hand, naturally occurring nanostructures in biology have been a source of inspiration for new nanotechnological designs and hybrid nanostructures made of biological and non-biological, organic and inorganic building blocks. Lipids, with their amphiphilicity, diversity of head and tail chemistry, and antifouling properties that block nonspecific binding to lipid-coated surfaces, provide a powerful toolbox for nanotechnology. This review discusses the progress in the emerging field of lipid nanotechnology.

  15. Antineoplastic treatment of patients with renal insufficiency

    International Nuclear Information System (INIS)

    Rajec, J.; Mego, M.; Rajec, J.

    2011-01-01

    Kidneys are the main route of elimination for many antineoplastic drugs and their metabolites. The kidney dysfunction may lead to the drug cumulation in organism with the resulting increased systemic toxicity. A lot of used cytostatics requires a dose modification at different levels of renal insufficiency. Due to the lack of data from clinical trials, the limiting of systemic toxicity is difficult especially in patients with severe renal impairment or patients undergoing chronic hemodialysis. The following article is focused on the preventive strategies dealing with recommended dosing modification of various antineoplastic agents in patients with renal insufficiency. (author)

  16. Pyrene-Labeled Amphiphiles: Dynamic And Structural Probes Of Membranes And Lipoproteins

    Science.gov (United States)

    Pownall, Henry J.; Homan, Reynold; Massey, John B.

    1987-01-01

    Lipids and proteins are important functional and structural components of living organisms. Although proteins are frequently found as soluble components of plasma or the cell cytoplasm, many lipids are much less soluble and separate into complex assemblies that usually contain proteins. Cell membranes and plasma lipoproteins' are two important macro-molecular assemblies that contain both lipids and proteins. Cell membranes are composed of a variety of lipids and proteins that form an insoluble bilayer array that has relatively little curvature over distances of several nm. Plasma lipoproteins are different in that they are much smaller, water-soluble, and have highly curved surfaces. A model of a high density lipoprotein (HDL) is shown in Figure 1. This model (d - 10 nm) contains a surface of polar lipids and proteins that surrounds a small core of insoluble lipids, mostly triglycerides and cholesteryl esters. The low density (LDL) (d - 25 nm) and very low density (VLDL) (d 90 nm) lipoproteins have similar architectures, except the former has a cholesteryl ester core and the latter a core that is almost exclusively triglyceride (Figure 1). The surface proteins of HDL are amphiphilic and water soluble; the single protein of LDL is insoluble, whereas VLDL contains both soluble and insoluble proteins. The primary structures of all of these proteins are known.

  17. Fluctuations and structure of amphiphilic films; Fluctuations et structure de films d`amphiphiles

    Energy Technology Data Exchange (ETDEWEB)

    Gourier, CH

    1996-07-01

    This thesis is divided in three parts.The first part exposes in a theoretical point of view, how the fluctuations spectrum of an amphiphilic film is governed by its properties and its bidimensional characteristics.The measurements of fluctuations spectra of an interface are accessible with the measurement of intensity that interface diffuses out of the specular angle, we present in the second chapter the principles of the X rays diffusion by a real interface and see how the diffuse diffusion experiments allow to determine the fluctuations spectrum of an amphiphilic film. The second part is devoted to the different experimental techniques that have allowed to realize the study of fluctuation as well as the structural study.The third part is devoted to experimental results concerning the measurements of fluctuations spectra and to the study of the structure of amphiphilic films. We show that it is possible by using an intense source of X rays (ESRF: European Synchrotron Radiation Facility) to measure the water and amphiphilic films fluctuations spectra until molecular scales. The last chapter is devoted to the structural study and film fluctuations made of di-acetylenic molecules. (N.C.)

  18. Regulation of sodium channel function by bilayer elasticity: the importance of hydrophobic coupling. Effects of Micelle-forming amphiphiles and cholesterol

    DEFF Research Database (Denmark)

    Lundbæk, Jens August; Birn, Pia; Hansen, Anker J

    2004-01-01

    , Triton X-100, and reduced Triton X-100) that make lipid bilayers less "stiff", as measured using gA channels, shift the voltage dependence of sodium channel inactivation toward more hyperpolarized potentials. At low amphiphile concentration, the magnitude of the shift is linearly correlated to the change...

  19. The non-peptidic part determines the internalization mechanism and intracellular trafficking of peptide amphiphiles.

    Directory of Open Access Journals (Sweden)

    Dimitris Missirlis

    Full Text Available BACKGROUND: Peptide amphiphiles (PAs are a class of amphiphilic molecules able to self-assemble into nanomaterials that have shown efficient in vivo targeted delivery. Understanding the interactions of PAs with cells and the mechanisms of their internalization and intracellular trafficking is critical in their further development for therapeutic delivery applications. METHODOLOGY/PRINCIPAL FINDINGS: PAs of a novel, cell- and tissue-penetrating peptide were synthesized possessing two different lipophilic tail architectures and their interactions with prostate cancer cells were studied in vitro. Cell uptake of peptides was greatly enhanced post-modification. Internalization occurred via lipid-raft mediated endocytosis and was common for the two analogs studied. On the contrary, we identified the non-peptidic part as the determining factor of differences between intracellular trafficking and retention of PAs. PAs composed of di-stearyl lipid tails linked through poly(ethylene glycol to the peptide exhibited higher exocytosis rates and employed different recycling pathways compared to ones consisting of di-palmitic-coupled peptides. As a result, cell association of the former PAs decreased with time. CONCLUSIONS/SIGNIFICANCE: Control over peptide intracellular localization and retention is possible by appropriate modification with synthetic hydrophobic tails. We propose this as a strategy to design improved peptide-based delivery systems.

  20. Preparation and Microbiological Evaluation of Amphiphilic Kanamycin-Lipoamino Acid Ion-Pairs

    Directory of Open Access Journals (Sweden)

    Rosario Pignatello

    2014-05-01

    Full Text Available Amphiphilic ion-pairs of kanamycin (KAN were prepared by evaporation of a water-ethanol co-solution of KAN base and a lipoamino acid bearing a 12-carbon atoms alkyl side chain (LAA12, at different molar ratios. Infrared spectroscopy confirmed the structure of ion-pairs, while differential scanning calorimetry (DSC and powder X-ray diffractometry (PXRD studies supported the formation of new saline species with a different crystalline structure than the starting components. The solubility pattern shown in a range of both aqueous and organic solvents confirmed that the ion-pairs possess an amphiphilic character. The LAA12 counter-ion showed not to improve the antibacterial activity of KAN, suggesting that such chemical strategy is not able to favor the penetration of this drug inside the bacteria cells. Nevertheless, a slight improving, i.e., a one-fold dilution, was observed in E. coli. The present study can also serve as the basis for a further evaluation of LAA ion-pairing of antibiotics, as a means to improve the loading of hydrophilic drugs into lipid-based nanocarriers.

  1. ANIONIC SYNTHESIS OF A "CLICKABLE" MIDDLE-CHAIN AZIDEFUNCTIONALIZED POLYSTYRENE AND ITS APPLICATION IN SHAPE AMPHIPHILES

    Institute of Scientific and Technical Information of China (English)

    Kan Yue; Jinlin He; Chang Liu; Mingjun Huang; Xue-Hui Dong; Kai Guo; Peihong Ni

    2013-01-01

    "Click chemistry" is,by definition,a general functionalization methodology (GFM) and its marriage with living anionic polymerization is particularly powerful in precise macromolecular synthesis.This paper reports the synthesis of a "clickable" middle-chain azide-functionalized polystyrene (mPS-N3) by anionic polymerization and its application in the preparation of novel shape amphiphiles based on polyhedral oligomeric silsesquioxane (POSS).The mPS-N3 was synthesized by coupling living poly(styryl)lithium chains (PSLi) with 3-chloropropylmethyldichlorosilane and subsequent nucleophilic substitution of the chloro group in the presence of sodium azide.Excess PSLi was end-capped with ethylene oxide to facilitate its removal by flash chromatography.The mPS-N3 was then derived into a giant lipid-like shape amphiphile in two steps following a sequential "click" strategy.The copper(I)-catalyzed azide-alkyne cycloaddition between mPS-N3 and alkyne-functionalized vinyl-substituted POSS derivative (VPOSS-alkyne) ensured quantitative ligation to give polystyrene with VPOSS tethered at the middle of the chain (mPS-VPOSS).The thiol-ene reaction with 1-thioglycerol transforms the vinyl groups on the POSS periphery to hydroxyls,resulting in an amphiphilic shape amphiphile,mPS-DPOSS.This synthetic approach is highly efficient and modular.It demonstrates the "click" philosophy of facile complex molecule construction from a library of simple building blocks and also suggests that mPS-N3 can be used as a versatile "clickable" motif in polymer science for the precise synthesis of complex macromolecules.

  2. H-shaped supra-amphiphiles based on a dynamic covalent bond.

    Science.gov (United States)

    Wang, Guangtong; Wang, Chao; Wang, Zhiqiang; Zhang, Xi

    2012-10-16

    The imine bond, a kind of dynamic covalent bond, is used to bind two bolaform amphiphiles together with spacers, yielding H-shaped supra-amphiphiles. Micellar aggregates formed by the self-assembly of the H-shaped supra-amphiphiles are observed. When pH is tuned down from basic to slightly acidic, the benzoic imine bond can be hydrolyzed, leading to the dissociation of H-shaped supra-amphiphiles. Moreover, H-shaped supra-amphiphiles have a lower critical micelle concentration than their building blocks, which is very helpful in enhancing the stability of the benzoic imine bond being hydrolyzed by acid. The surface tension isotherms of the H-shaped supra-amphiphiles with different spacers indicate their twisty conformation at a gas-water interface. The study of H-shaped supra-amphiphiles can enrich the family of amphiphiles, and moreover, the pH-responsiveness may make them apply to controlled or targetable drug delivery in a biological environment.

  3. The Hepatoprotection Provided by Taurine and Glycine against Antineoplastic Drugs Induced Liver Injury in an Ex Vivo Model of Normothermic Recirculating Isolated Perfused Rat Liver

    Directory of Open Access Journals (Sweden)

    Reza Heidari

    2016-03-01

    Full Text Available Taurine (2-aminoethane sulfonic acid is a non-protein amino acid found in high concentration in different tissues. Glycine (Amino acetic acid is the simplest amino acid incorporated in the structure of proteins. Several investigations indicate the hepatoprotective properties of these amino acids. On the other hand, antineoplastic agents-induced serum transaminase elevation and liver injury is a clinical complication. The current investigation was designed to screen the possible hepatoprotective properties of taurine and glycine against antineoplastic drugs-induced hepatic injury in an ex vivo model of isolated perfused rat liver. Rat liver was perfused with different concentration (10 μM, 100 μM and 1000 μM of antineoplastic drugs (Mitoxantrone, Cyclophosphamide, Cisplatin, 5 Fluorouracil, Doxorubicin and Dacarbazine via portal vein. Taurine and glycine were administered to drug-treated livers and liver perfusate samples were collected for biochemical measurements (ALT, LDH, AST, and K+. Markers of oxidative stress (reactive oxygen species formation, lipid peroxidation, total antioxidant capacity and glutathione were also assessed in liver tissue. Antineoplastic drugs caused significant pathological changes in perfusate biochemistry. Furthermore, markers of oxidative stress were significantly elevated in drug treated livers. It was found that taurine (5 and 10 mM and glycine (5 and 10 mM administration significantly mitigated the biomarkers of liver injury and attenuated drug induced oxidative stress. Our data indicate that taurine and glycine supplementation might help as potential therapeutic options to encounter anticancer drugs-induced liver injury.

  4. Impact of amphiphilic molecules on the structure and stability of homogeneous sphingomyelin bilayer: Insights from atomistic simulations

    Science.gov (United States)

    Kumari, Pratibha; Kaur, Supreet; Sharma, Shobha; Kashyap, Hemant K.

    2018-04-01

    Modulation of lipid membrane properties due to the permeation of amphiphiles is an important biological process pertaining to many applications in the field of pharmaceutics, toxicology, and biotechnology. Sphingolipids are both structural and functional lipids that constitute an important component of mechanically stable and chemically resistant outer leaflets of plasma membranes. Here, we present an atomistic molecular dynamics simulation study to appreciate the concentration-dependent effects of small amphiphilic molecules, such as ethanol, acetone, and dimethyl sulfoxide (DMSO), on the structure and stability of a fully hydrated homogeneous N-palmitoyl-sphingomyelin (PSM) bilayer. The study reveals an increase in the lateral expansion of the bilayer along with disordering of the hydrophobic lipid tails on increasing the concentration of ethanol. At higher concentrations of ethanol, rupturing of the bilayer is quite evident through the analysis of partial electron density profiles and lipid tail order parameters. For ethanol containing systems, permeation of water molecules in the hydrophobic part of the bilayer is allowed through local defects made due to the entry of ethanol molecules via ethanol-ethanol and ethanol-PSM hydrogen bonds. Moreover, the extent of PSM-PSM hydrogen bonding decreases with increasing ethanol concentration. On the other hand, acetone and DMSO exhibit minimal effects on the stability of the PSM bilayer at their lower concentrations, but at higher concentrations they tend to enhance the stability of the bilayer. The simulated potential of mean force (PMF) profiles for the translocation of the three solutes studied reveal that the free-energy of transfer of an ethanol molecule across the PSM lipid head region is lower than that for acetone and DMSO molecules. However, highest free-energy rise in the core hydrophobic part of the bilayer is observed for the DMSO molecule, whereas the ethanol and acetone PMF profiles show a lower barrier in

  5. Disassembly Control of Saccharide-Based Amphiphiles Driven by Electrostatic Repulsion.

    Science.gov (United States)

    Yamada, Taihei; Kokado, Kenta; Sada, Kazuki

    2017-03-14

    According to the design of disassembly using electrostatic repulsion, novel amphiphiles consisting of a lipophilic ion part and a hydrophilic saccharide part were synthesized via the facile copper-catalyzed click reaction, and their molecular assemblies in water and chloroform were studied. The amphiphiles exhibited a molecular orientation opposite to that of the conventional amphiphiles in each case. ζ Potential measurements indicated that the lipophilic ion part is exposed outside in chloroform. The size of a solvophobic part in the amphiphiles dominates the size of an assembling structure; that is, in water, these amphiphiles tethering different lengths of the saccharide part exhibited almost identical assembling size, whereas in chloroform, the size depends on the length of the saccharide part in the amphiphiles.

  6. Computational Amphiphilic Materials for Drug Delivery

    Directory of Open Access Journals (Sweden)

    Naresh eThota

    2015-10-01

    Full Text Available Amphiphilic materials can assemble into a wide variety of morphologies and have emerged as a novel class of candidates for drug delivery. Along with a large number of experiments reported, computational studies have been also conducted in this field. At an atomistic/molecular level, computations can facilitate quantitative understanding of experimental observations and secure fundamental interpretation of underlying phenomena. This review summarizes the recent computational efforts on amphiphilic copolymers and peptides for drug delivery. Atom-resolution and time-resolved insights are provided from bottom-up to microscopically elucidate the mechanisms of drug loading/release, which are indispensable in the rational screening and design of new amphiphiles for high-efficacy drug delivery.

  7. Preparation and self-assembly of amphiphilic polylysine dendrons

    DEFF Research Database (Denmark)

    Mirsharghi, Sahar; Knudsen, Kenneth D.; Bagherifam, Shahla

    2016-01-01

    Polylysine dendrons with lipid tails prepared by divergent solid-phase synthesis showed self-assembling properties in aqueous solutions., Herein, we present the synthesis of new amphiphilic polylysine dendrons with variable alkyl chain lengths (C1–C18) at the C-terminal. The dendrons were...... synthesized in moderate to quantitative yields by divergent solid-phase synthesis (SPS) employing an aldehyde linker. The self-assembling properties of the dendrons in aqueous solutions were studied by small angle neutron scattering (SANS) and dynamic light scattering (DLS). The self-assembling properties...... were influenced by the length of the alkyl chain and the generation number (Gn). Increasing the temperature and concentration did not have significant impact on the hydrodynamic diameter, but the self-assembling properties were influenced by the pH value. This demonstrated the need for positively...

  8. Tandem Facial Amphiphiles for Membrane Protein Stabilization

    DEFF Research Database (Denmark)

    Chae, Pil Seok; Gotfryd, Kamil; Pacyna, Jennifer

    2010-01-01

    We describe a new type of synthetic amphiphile that is intended to support biochemical characterization of intrinsic membrane proteins. Members of this new family displayed favorable behavior with four of five membrane proteins tested, and these amphiphiles formed relatively small micelles....

  9. Lipophosphoramidate-based bipolar amphiphiles: their syntheses and transfection properties.

    Science.gov (United States)

    Berchel, Mathieu; Le Gall, Tony; Lozach, Olivier; Haelters, Jean-Pierre; Montier, Tristan; Jaffrès, Paul-Alain

    2016-03-14

    Six new cationic bolaamphiphiles (also called bipolar amphiphiles, bolaform amphiphiles, or bolalipids) were readily prepared by a thiol-ene click reaction that engaged a mercapto-alcohol (mercapto-ethanol or mercapto-hexanol) and a cationic based lipophosphoramidate. The cationic lipophosphoramidates contain two lipid chains that end in an alkene group and a selected cationic polar head group (trimethylammonium, dimethyl hydroxyethyl ammonium, or methylimidazolium). These compounds were formulated in water (with or without DOPE as a colipid) to produce supramolecular aggregates. These aggregates, before (i.e. bolasomes) and after (i.e. bolaplexes) mixing with plasmid DNA (pDNA) at various charge ratios, were characterized with regard to their sizes and zeta potentials. In the case of bolasomes, the suspensions were unstable since precipitation occurred after only a few hours at room temperature. On the other hand, bolaplex formulations exhibited clearly a better colloidal stability. Then, the gene delivery properties of the cationic bolasomes were investigated using two human-derived epithelial cell lines (A549 and 16HBE). Compared to the commercially available lipofection reagent (Lipofectamine), most of the cationic bolaamphiphiles were able to efficiently transfect these cells when they were formulated with DOPE in a 1 : 1 molar ratio. We report herein that bolaamphiphiles possessing a trimethylammonium or a dimethyl hydroxyethyl ammonium head group were the most efficient in terms of transfection efficiency while exhibiting no significant cytotoxicity.

  10. Co-assembly of Peptide Amphiphiles and Lipids into Supramolecular Nanostructures Driven by Anion-π Interactions

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Zhilin; Erbas, Aykut; Tantakitti, Faifan; Palmer, Liam C.; Jackman, Joshua A.; Olvera de la Cruz, Monica; Cho, Nam-Joon; Stupp, Samuel I. (Nanyang); (NWU)

    2017-06-01

    Co-assembly of binary systems driven by specific non-covalent interactions can greatly expand the structural and functional space of supramolecular nanostructures. We report here on the self-assembly of peptide amphiphiles and fatty acids driven primarily by anion-π interactions. The peptide sequences investigated were functionalized with a perfluorinated phenylalanine residue to promote anion-π interactions with carboxylate headgroups in fatty acids. These interactions were verified here by NMR and circular dichroism experiments as well as investigated using atomistic simulations. Positioning the aromatic units close to the N-terminus of the peptide backbone near the hydrophobic core of cylindrical nanofibers leads to strong anion-π interactions between both components. With a low content of dodecanoic acid in this position, the cylindrical morphology is preserved. However, as the aromatic units are moved along the peptide backbone away from the hydrophobic core, the interactions with dodecanoic acid transform the cylindrical supramolecular morphology into ribbon-like structures. Increasing the ratio of dodecanoic acid to PA leads to either the formation of large vesicles in the binary systems where the anion-π interactions are strong, or a heterogeneous mixture of assemblies when the peptide amphiphiles associate weakly with dodecanoic acid. Our findings reveal how co-assembly involving designed specific interactions can drastically change supramolecular morphology and even cross from nano to micro scales.

  11. Highly ordered self-assembly of one-dimensional nanoparticles in amphiphilic molecular systems

    International Nuclear Information System (INIS)

    Kim, Tae Hwan

    2009-02-01

    cationic surfactant, CTVB which has polymerizable counterions, and 2) permanently fixing the surfactant monolayer on the SWNTs by in situ free radical polymerization of the counterions, followed by freeze drying. UV-vis-NIR spectra of p-SWNT in water and alcohol showed very sharp van Hove transition which is typical for isolated SWNT, and were essentially identical after redispersion, indicating the excellent redispersibility. The in-situ microstructures of the p-SWNTs dispersed in water and alcohols were measured with SANS, which showed the encapsulation of SWNT by the surfactant monolayer cylindrically and by a swollen polymerized surfactant layer, respectively. It should be noted that the p-SWNTs are readily redispersible in water or alcohol by only 10 minutes of mild vortex mixing after harsh processing such as freeze-drying. Two kinds of cationic liposomes (CLs) consisting of univalent cationic and zwitterionic lipids were used as the amphiphilic molecular template for the interaction with 1D nanoparticles. For highly ordered superstructure of the cROD n (n is the number of carbon in the alkyl chain) in amphiphilic molecular systems, the CLs composed of DOTAP (catioinc) and DOPC (zwitterionic) lipids with various ratios (5:5 and 3:7) were prepared. The small angle x-ray scattering (SAXS) intensities of cROD n -DOTAP/DOPC complexes showed three different highly ordered phases, intercalated lamellar, doubly intercalated lamellar and centered rectangular phases, depending on particle diameter and charge interactions between cROD n and CLs. The phase behavior of cROD n -CL complexes was explained by the d spacing /d rod ratio and a new phase diagram of the complexes was established. It should be noted that the centered rectangular columnar phase of 1D nanoparticle-CL complexes has not been previously reported while the intercalated lamellar and the doubly intercalated lamellar structures were observed in rod-like biomolecule-CL complexes. For highly ordered superstructure

  12. Fluctuations and structure of amphiphilic films

    International Nuclear Information System (INIS)

    Gourier, CH.

    1996-01-01

    This thesis is divided in three parts.The first part exposes in a theoretical point of view, how the fluctuations spectrum of an amphiphilic film is governed by its properties and its bidimensional characteristics.The measurements of fluctuations spectra of an interface are accessible with the measurement of intensity that interface diffuses out of the specular angle, we present in the second chapter the principles of the X rays diffusion by a real interface and see how the diffuse diffusion experiments allow to determine the fluctuations spectrum of an amphiphilic film. The second part is devoted to the different experimental techniques that have allowed to realize the study of fluctuation as well as the structural study.The third part is devoted to experimental results concerning the measurements of fluctuations spectra and to the study of the structure of amphiphilic films. We show that it is possible by using an intense source of X rays (ESRF: European Synchrotron Radiation Facility) to measure the water and amphiphilic films fluctuations spectra until molecular scales. The last chapter is devoted to the structural study and film fluctuations made of di-acetylenic molecules. (N.C.)

  13. GABA_A receptor function is regulated by lipid bilayer elasticity

    DEFF Research Database (Denmark)

    Søgaard, Rikke; Werge, Thomas; Berthelsen, Camilla

    2006-01-01

    ( s) underlying these effects are poorly understood. DHA and Triton X-100, at concentrations that affect GABAA receptor function, increase the elasticity of lipid bilayers measured as decreased bilayer stiffness using gramicidin channels as molecular force transducers. We have previously shown...... reduced the peak amplitude of the GABA-induced currents and increased the rate of receptor desensitization. The effects of the amphiphiles did not correlate with the expected changes in monolayer spontaneous curvature. We conclude that GABAA receptor function is regulated by lipid bilayer elasticity....... PUFAs may generally regulate membrane protein function by affecting the elasticity of the host lipid bilayer....

  14. Freezing-induced self-assembly of amphiphilic molecules

    Science.gov (United States)

    Albouy, P. A.; Deville, S.; Fulkar, A.; Hakouk, K.; Impéror-Clerc, M.; Klotz, M.; Liu, Q.; Marcellini, M.; Perez, J.

    The self-assembly of amphiphilic molecules usually takes place in a liquid phase, near room temperature. Here, using small angle X-ray scattering (SAXS) experiments performed in real time, we show that freezing of aqueous solutions of copolymer amphiphilic molecules can induce self-assembly below 0{\\deg}C.

  15. Monoolein lipid phases as incorporation and enrichment materials for membrane protein crystallization.

    Directory of Open Access Journals (Sweden)

    Ellen Wallace

    Full Text Available The crystallization of membrane proteins in amphiphile-rich materials such as lipidic cubic phases is an established methodology in many structural biology laboratories. The standard procedure employed with this methodology requires the generation of a highly viscous lipidic material by mixing lipid, for instance monoolein, with a solution of the detergent solubilized membrane protein. This preparation is often carried out with specialized mixing tools that allow handling of the highly viscous materials while minimizing dead volume to save precious membrane protein sample. The processes that occur during the initial mixing of the lipid with the membrane protein are not well understood. Here we show that the formation of the lipidic phases and the incorporation of the membrane protein into such materials can be separated experimentally. Specifically, we have investigated the effect of different initial monoolein-based lipid phase states on the crystallization behavior of the colored photosynthetic reaction center from Rhodobacter sphaeroides. We find that the detergent solubilized photosynthetic reaction center spontaneously inserts into and concentrates in the lipid matrix without any mixing, and that the initial lipid material phase state is irrelevant for productive crystallization. A substantial in-situ enrichment of the membrane protein to concentration levels that are otherwise unobtainable occurs in a thin layer on the surface of the lipidic material. These results have important practical applications and hence we suggest a simplified protocol for membrane protein crystallization within amphiphile rich materials, eliminating any specialized mixing tools to prepare crystallization experiments within lipidic cubic phases. Furthermore, by virtue of sampling a membrane protein concentration gradient within a single crystallization experiment, this crystallization technique is more robust and increases the efficiency of identifying productive

  16. Antineoplastic drugs: Occupational exposure and health risks

    NARCIS (Netherlands)

    Fransman, W.

    2006-01-01

    Antineoplastic drugs are pharmaceuticals commonly used to treat cancer (and some non-neoplastic diseases), which are generally referred to as 'chemotherapy'. Oncology nurses are exposed to these drugs via the skin of hands during daily nursing activities, even when protective gloves are being used.

  17. Impact of Robotic Antineoplastic Preparation on Safety, Workflow, and Costs

    Science.gov (United States)

    Seger, Andrew C.; Churchill, William W.; Keohane, Carol A.; Belisle, Caryn D.; Wong, Stephanie T.; Sylvester, Katelyn W.; Chesnick, Megan A.; Burdick, Elisabeth; Wien, Matt F.; Cotugno, Michael C.; Bates, David W.; Rothschild, Jeffrey M.

    2012-01-01

    Purpose: Antineoplastic preparation presents unique safety concerns and consumes significant pharmacy staff time and costs. Robotic antineoplastic and adjuvant medication compounding may provide incremental safety and efficiency advantages compared with standard pharmacy practices. Methods: We conducted a direct observation trial in an academic medical center pharmacy to compare the effects of usual/manual antineoplastic and adjuvant drug preparation (baseline period) with robotic preparation (intervention period). The primary outcomes were serious medication errors and staff safety events with the potential for harm of patients and staff, respectively. Secondary outcomes included medication accuracy determined by gravimetric techniques, medication preparation time, and the costs of both ancillary materials used during drug preparation and personnel time. Results: Among 1,421 and 972 observed medication preparations, we found nine (0.7%) and seven (0.7%) serious medication errors (P = .8) and 73 (5.1%) and 28 (2.9%) staff safety events (P = .007) in the baseline and intervention periods, respectively. Drugs failed accuracy measurements in 12.5% (23 of 184) and 0.9% (one of 110) of preparations in the baseline and intervention periods, respectively (P < .001). Mean drug preparation time increased by 47% when using the robot (P = .009). Labor costs were similar in both study periods, although the ancillary material costs decreased by 56% in the intervention period (P < .001). Conclusion: Although robotically prepared antineoplastic and adjuvant medications did not reduce serious medication errors, both staff safety and accuracy of medication preparation were improved significantly. Future studies are necessary to address the overall cost effectiveness of these robotic implementations. PMID:23598843

  18. Revealing Amphiphilic Nanodornains of Anti-Biofouling Polymer Coatings

    Energy Technology Data Exchange (ETDEWEB)

    Amadei, CA; Yang, R; Chiesa, M; Gleason, KK; Santos, S

    2014-04-09

    Undesired bacterial adhesion and biofilm formation on wetted surfaces leads to significant economic and environmental costs in various industries. Amphiphilic coatings with molecular hydrophilic and hydrophobic patches can mitigate such biofouling effectively in an environmentally friendly manner. The coatings are synthesized by copolymerizing (Hydroxyethyl)methacrylate and perfluorodecylacrylate via initiated chemical vapor deposition (iCVD). In previous studies, the size of the patches was estimated to be similar to 1.4-1.75 nm by fitting protein adsorption data to a theoretical model. However, no direct observations of the molecular heterogeneity exist and therefore the origin of the fouling resistance of amphiphilic coatings remains unclear. Here, the amphiphilic nature is investigated by amplitude modulation atomic force microscopy (AM-AFM). High-resolution images obtained by penetrating and oscillating the AFM tip under the naturally present water layer with sub-nanometer amplitudes reveal, for the first time, the existence of amphiphilic nanodomains (1-2 nm(2)). Compositional heterogeneity at the nanoscale is further corroborated by a statistical analysis on the data obtained with dynamic AM-AFM force spectroscopy. Variations in the long range attractive forces, responsible for water affinity, are also identified. These nanoscopic results on the polymers wettability are also confirmed by contact angle measurements (i.e., static and dynamic). The unprecedented ability to visualize the amphiphilic nanodomains as well as sub-nanometer crystalline structures provides strong evidence for the existence of previously postulated nanostructures, and sheds light on the underlying antifouling mechanism of amphiphilic chemistry.

  19. Amphiphilic block copolymers for biomedical applications

    Science.gov (United States)

    Zupancich, John Andrew

    Amphiphilic block copolymer self-assembly provides a versatile means to prepare nanoscale objects in solution. Control over aggregate shape is granted through manipulation of amphiphile composition and the synthesis of well-defined polymers offers the potential to produce micelles with geometries optimized for specific applications. Currently, polymer micelles are being investigated as vehicles for the delivery of therapeutics and attempts to increase efficacy has motivated efforts to incorporate bioactive ligands and stimuli-responsive character into these structures. This thesis reports the synthesis and self-assembly of biocompatible, degradable polymeric amphiphiles. Spherical, cylindrical, and bilayered vesicle structures were generated spontaneously by the direct dispersion of poly(ethylene oxide)-b-poly(gamma-methyl-ε-caprolactone) block copolymers in water and solutions were characterized with cryogenic transmission electron microscopy (cryo-TEM). The dependence of micelle structure on diblock copolymer composition was examined through the systematic variation of the hydrophobic block molecular weight. A continuous evolution of morphology was observed with coexistence of aggregate structures occurring in windows of composition intermediate to that of pure spheres, cylinders and vesicles. A number of heterobifunctional poly(ethylene oxide) polymers were synthesized for the preparation of ligand-functionalized amphiphilic diblock copolymers. The effect of ligand conjugation on block copolymer self-assembly and micelle morphology was also examined. An RGD-containing peptide sequence was efficiently conjugated to a set of well characterized poly(ethylene oxide)-b-poly(butadiene) copolymers. The reported aggregate morphologies of peptide-functionalized polymeric amphiphiles deviated from canonical structures and the micelle clustering, cylinder fragmentation, network formation, and multilayer vesicle generation documented with cryo-TEM was attributed to

  20. Mesenchymal Stromal Cells for Antineoplastic Drug Loading and Delivery.

    Science.gov (United States)

    Petrella, Francesco; Rimoldi, Isabella; Rizzo, Stefania; Spaggiari, Lorenzo

    2017-11-23

    Mesenchymal stromal cells are a population of undifferentiated multipotent adult cells possessing extensive self-renewal properties and the potential to differentiate into a variety of mesenchymal lineage cells. They express broad anti-inflammatory and immunomodulatory activity on the immune system and after transplantation can interact with the surrounding microenvironment, promoting tissue healing and regeneration. For this reason, mesenchymal stromal cells have been widely used in regenerative medicine, both in preclinical and clinical settings. Another clinical application of mesenchymal stromal cells is the targeted delivery of chemotherapeutic agents to neoplastic cells, maximizing the cytotoxic activity against cancer cells and minimizing collateral damage to non-neoplastic tissues. Mesenchymal stem cells are home to the stroma of several primary and metastatic neoplasms and hence can be used as vectors for targeted delivery of antineoplastic drugs to the tumour microenvironment, thereby reducing systemic toxicity and maximizing antitumour effects. Paclitaxel and gemcitabine are the chemotherapeutic drugs best loaded by mesenchymal stromal cells and delivered to neoplastic cells, whereas other agents, like pemetrexed, are not internalized by mesenchymal stromal cells and therefore are not suitable for advanced antineoplastic therapy. This review focuses on the state of the art of advanced antineoplastic cell therapy and its future perspectives, emphasizing in vitro and in vivo preclinical results and future clinical applications.

  1. The Rheological Properties of Lipid Monolayers Modulate the Incorporation of l-Ascorbic Acid Alkyl Esters.

    Science.gov (United States)

    Díaz, Yenisleidy de Las Mercedes Zulueta; Mottola, Milagro; Vico, Raquel V; Wilke, Natalia; Fanani, María Laura

    2016-01-19

    In this work, we tested the hypothesis that the incorporation of amphiphilic drugs into lipid membranes may be regulated by their rheological properties. For this purpose, two members of the l-ascorbic acid alkyl esters family (ASCn) were selected, ASC16 and ASC14, which have different rheological properties when organized at the air/water interface. They are lipophilic forms of vitamin C used in topical pharmacological preparations. The effect of the phase state of the host lipid membranes on ASCn incorporation was explored using Langmuir monolayers. Films of pure lipids with known phase states have been selected, showing liquid-expanded, liquid-condensed, and solid phases as well as pure cholesterol films in liquid-ordered state. We also tested ternary and quaternary mixed films that mimic the properties of cholesterol containing membranes and of the stratum corneum. The compressibility and shear properties of those monolayers were assessed in order to define its phase character. We found that the length of the acyl chain of the ASCn compounds induces differential changes in the rheological properties of the host membrane and subtly regulates the kinetics and extent of the penetration process. The capacity for ASCn uptake was found to depend on the phase state of the host film. The increase in surface pressure resultant after amphiphile incorporation appears to be a function of the capacity of the host membrane to incorporate such amphiphile as well as the rheological response of the film. Hence, monolayers that show a solid phase state responded with a larger surface pressure increase to the incorporation of a comparable amount of amphiphile than liquid-expanded ones. The cholesterol-containing films, including the mixture that mimics stratum corneum, allowed a very scarce ASCn uptake independently of the membrane diffusional properties. This suggests an important contribution of Cho on the maintenance of the barrier function of stratum corneum.

  2. Supra-amphiphiles: a new bridge between colloidal science and supramolecular chemistry.

    Science.gov (United States)

    Kang, Yuetong; Liu, Kai; Zhang, Xi

    2014-06-03

    In addition to conventional amphiphiles, an emerging research area is supra-amphiphiles, which are constructed on the basis of noncovalent interactions and dynamic covalent bonds. In this feature article, we have provided a general introduction to the concept, design principles, and topologies of supra-amphiphiles, starting from some rationally tailored building blocks. In addition, we highlight some progress in the functional assembly of supra-amphiphiles, such as responsive nanoscale carriers, antibacterial and antitumor agents, fluorescent-based chemical sensors, and enzyme mimics. The supra-amphiphile is a new bridge between colloidal science and supramolecular chemistry, and it is a field where we can make full use of our imaginative power.

  3. Investigation of antineoplastic activity of chewing tablets based on dry oat extract and quercetin

    Directory of Open Access Journals (Sweden)

    Ярослав Ростиславович Андрійчук

    2015-07-01

    Full Text Available One of the main goals of domestic pharmaceutical science is development of new medicines. Thus, new tablet drug was created based on dry oat extract and quercetin. Investigation of antineoplastic activity was performed. Antineoplastic activity of investigational drug based on dry oat extract and quercetin was experimentally proved.

  4. Multicompartment lipid cubic nanoparticles with high protein upload: millisecond dynamics of formation

    Czech Academy of Sciences Publication Activity Database

    Angelov, Borislav; Angelova, A.; Filippov, Sergey K.; Drechsler, M.; Štěpánek, Petr; Lesieur, S.

    2014-01-01

    Roč. 8, č. 5 (2014), s. 5216-5226 ISSN 1936-0851 R&D Projects: GA ČR GAP208/10/1600 Institutional support: RVO:61389013 Keywords : lipid- protein nanoassembly * dynamic membrane curvature * amphiphile nanoarchitectonics Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 12.881, year: 2014

  5. The effects of ethylene oxide containing lipopolymers and tri-block copolymers on lipid bilayers of dipalmitoylphosphatidylcholine

    DEFF Research Database (Denmark)

    Baekmark, T. R.; Pedersen, S.; Jorgensen, K.

    1997-01-01

    oxide moity, anchored to the bilayer by a 1,2-dioctadecanoyl-s,n-glycero-3-phosphoethanolamine (DC18PE) lipid. The second type, which is a novel type of membrane-spanning object, is an amphiphilic tri-block copolymer composed of two hydrophilic stretches of polyethylene oxide separated by a hydrophobic...... stretch of polystyrene. Hence the tri-block copolymer may act as a membrane-spanning macromolecule mimicking an amphiphilic protein or polypeptide. Differential scanning calorimetry is used to determine a partial phase diagram for the lipopolymer systems and to assess the amount of lipopolymer that can...... be loaded into DC16PC lipid bilayers before micellization takes place. Unilamellar and micellar phase structures are investigated by fluorescence quenching using bilayer permeating dithionite. The chain length-dependent critical lipopolymer concentration, denoting the lamellar-to-micellar phase transition...

  6. Preparation and Characterization of Amphiphilic Triblock Terpolymer-Based Nanofibers as Antifouling Biomaterials

    KAUST Repository

    Cho, Youngjin

    2012-05-14

    Antifouling surfaces are critical for the good performance of functional materials in various applications including water filtration, medical implants, and biosensors. In this study, we synthesized amphiphilic triblock terpolymers (tri-BCPs, coded as KB) and fabricated amphiphilic nanofibers by electrospinning of solutions prepared by mixing the KB with poly(lactic acid) (PLA) polymer. The resulting fibers with amphiphilic polymer groups exhibited superior antifouling performance to the fibers without such groups. The adsorption of bovine serum albumin (BSA) on the amphiphilic fibers was about 10-fold less than that on the control surfaces from PLA and PET fibers. With the increase of the KB content in the amphiphilic fibers, the resistance to adsorption of BSA was increased. BSA was released more easily from the surface of the amphiphilic fibers than from the surface of hydrophobic PLA or PET fibers. We have also investigated the structural conformation of KB in fibers before and after annealing by contact angle measurements, transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDX), and coarse-grained molecular dynamics (CGMD) simulation to probe the effect of amphiphilic chain conformation on antifouling. The results reveal that the amphiphilic KB was evenly distributed within as-spun hybrid fibers, while migrated toward the core from the fiber surface during thermal treatment, leading to the reduction in antifouling. This suggests that the antifouling effect of the amphiphilic fibers is greatly influenced by the arrangement of amphiphilic groups in the fibers. © 2012 American Chemical Society.

  7. The evolution of lipids

    Science.gov (United States)

    Itoh, Y. H.; Sugai, A.; Uda, I.; Itoh, T.

    2001-01-01

    Living organisms on the Earth which are divided into three major domains - Archaea, Bacteria, and Eucarya, probably came from a common ancestral cell. Because there are many thermophilic microorganisms near the root of the universal phylogenetic tree, the common ancestral cell should be considered to be a thermophilic microorganism. The existence of a cell is necessary for the living organisms; the cell membrane is the essential structural component of a cell, so its amphiphilic property is vital for the molecule of lipids for cell membranes. Tetraether type glycerophospholipids with C 40 isoprenoid chains are major membrane lipids widely distributed in archaeal cells. Cyclization number of C 40 isoprenoid chains in thermophilic archaea influences the fluidity of lipids whereas the number of carbons and degree of unsaturation in fatty acids do so in bacteria and eucarya. In addition to the cyclization of the tetraether lipids, covalent bonding of two C 40 isoprenoid chains was found in hyperthermophiles. These characteristic structures of the lipids seem to contribute to their fundamental physiological roles in hyperthermophiles. Stereochemical differences between G-1-P archaeal lipids and G-3-P bacterial and eucaryal lipids might have occured by the function of some proteins long after the first cell was developed by the reactions of small organic molecules. We propose that the structure of lipids of the common ancestral cell may have been similar to those of hyperthermophilic archaea.

  8. 75 FR 57044 - NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings 2010

    Science.gov (United States)

    2010-09-17

    ... identified 24 drugs that fit the NIOSH definition of hazardous drugs. The second draft list also proposed... Antineoplastic and Other Hazardous Drugs in Healthcare Settings 2010 AGENCY: National Institute for Occupational... publication of the following document entitled ``NIOSH List of Antineoplastic and Other Hazardous Drugs in...

  9. Lipase polystyrene giant amphiphiles.

    Science.gov (United States)

    Velonia, Kelly; Rowan, Alan E; Nolte, Roeland J M

    2002-04-24

    A new type of giant amphiphilic molecule has been synthesized by covalently connecting a lipase enzyme headgroup to a maleimide-functionalized polystyrene tail (40 repeat units). The resulting biohybrid forms catalytic micellar rods in water.

  10. Multilayers of Fluorinated Amphiphilic Polyions for Marine Fouling Prevention

    NARCIS (Netherlands)

    Zhu, X.; Guo, S.; Janczewski, D.; Parra-Velandia, F.J.; Teo, S.L-M.; Vancso, Gyula J.

    2014-01-01

    Sequential layer-by-layer (LbL) deposition of polyelectrolytes followed by chemical cross-linking was investigated as a method to fabricate functional amphiphilic surfaces for marine biofouling prevention applications. A novel polyanion, grafted with amphiphilic perfluoroalkyl polyethylene glycol

  11. SAXS Study of Sterically Stabilized Lipid Nanocarriers Functionalized by DNA

    Science.gov (United States)

    Angelov, Borislav; Angelova, Angelina; Filippov, Sergey; Karlsson, Göran; Terrill, Nick; Lesieur, Sylviane; Štěpánek, Petr

    2012-03-01

    The structure of novel spontaneously self-assembled plasmid DNA/lipid complexes is investigated by means of synchrotron radiation small-angle X-ray scattering (SAXS) and Cryo-TEM imaging. Liquid crystalline (LC) hydrated lipid systems are prepared using the non-ionic lipids monoolein and DOPE-PEG2000 and the cationic amphiphile CTAB. The employed plasmid DNA (pDNA) is encoding for the human protein brain-derived neurotrophic factor (BDNF). A coexistence of nanoparticulate objects with different LC inner organizations is established. A transition from bicontinuous membrane sponges, cubosome intermediates and unilamelar liposomes to multilamellar vesicles, functionalized by pDNA, is favoured upon binding and compaction of pBDNF onto the cationic PEGylated lipid nanocarriers. The obtained sterically stabilized multicompartment nanoobjects, with confined supercoiled plasmid DNA (pBDNF), are important in the context of multicompartment lipid nanocarriers of interest for gene therapy of neurodegenerative diseases.

  12. SAXS Study of Sterically Stabilized Lipid Nanocarriers Functionalized by DNA

    International Nuclear Information System (INIS)

    Angelov, Borislav; Filippov, Sergey; Štepánek, Petr; Angelova, Angelina; Lesieur, Sylviane; Karlsson, Göran; Terrill, Nick

    2012-01-01

    The structure of novel spontaneously self-assembled plasmid DNA/lipid complexes is investigated by means of synchrotron radiation small-angle X-ray scattering (SAXS) and Cryo-TEM imaging. Liquid crystalline (LC) hydrated lipid systems are prepared using the non-ionic lipids monoolein and DOPE-PEG 2000 and the cationic amphiphile CTAB. The employed plasmid DNA (pDNA) is encoding for the human protein brain-derived neurotrophic factor (BDNF). A coexistence of nanoparticulate objects with different LC inner organizations is established. A transition from bicontinuous membrane sponges, cubosome intermediates and unilamelar liposomes to multilamellar vesicles, functionalized by pDNA, is favoured upon binding and compaction of pBDNF onto the cationic PEGylated lipid nanocarriers. The obtained sterically stabilized multicompartment nanoobjects, with confined supercoiled plasmid DNA (pBDNF), are important in the context of multicompartment lipid nanocarriers of interest for gene therapy of neurodegenerative diseases.

  13. Recombinant Amphiphilic Protein Micelles for Drug Delivery

    OpenAIRE

    Kim, Wookhyun; Xiao, Jiantao; Chaikof, Elliot L.

    2011-01-01

    Amphiphilic block polypeptides can self-assemble into a range of nanostructures in solution, including micelles and vesicles. Our group has recently described the capacity of recombinant amphiphilic diblock copolypeptides to form highly stable micelles. In this report, we demonstrate the utility of protein nanoparticles to serve as a vehicle for controlled drug delivery. Drug-loaded micelles were produced by encapsulating dipyridamole as a model hydrophobic drug with anti-inflammatory activit...

  14. Glucose-neopentyl glycol (GNG) amphiphiles for membrane protein study

    DEFF Research Database (Denmark)

    Chae, Pil Seok; Rana, Rohini R; Gotfryd, Kamil

    2013-01-01

    The development of a new class of surfactants for membrane protein manipulation, "GNG amphiphiles", is reported. These amphiphiles display promising behavior for membrane proteins, as demonstrated recently by the high resolution structure of a sodium-pumping pyrophosphatase reported by Kellosalo ...

  15. Cathepsin-Mediated Cleavage of Peptides from Peptide Amphiphiles Leads to Enhanced Intracellular Peptide Accumulation

    Energy Technology Data Exchange (ETDEWEB)

    Acar, Handan [Institute; Department; Samaeekia, Ravand [Institute; Department; Schnorenberg, Mathew R. [Institute; Department; Medical; Sasmal, Dibyendu K. [Institute; Huang, Jun [Institute; Tirrell, Matthew V. [Institute; Institute; LaBelle, James L. [Department

    2017-08-24

    Peptides synthesized in the likeness of their native interaction domain(s) are natural choices to target protein protein interactions (PPIs) due to their fidelity of orthostatic contact points between binding partners. Despite therapeutic promise, intracellular delivery of biofunctional peptides at concentrations necessary for efficacy remains a formidable challenge. Peptide amphiphiles (PAs) provide a facile method of intracellular delivery and stabilization of bioactive peptides. PAs consisting of biofunctional peptide headgroups linked to hydrophobic alkyl lipid-like tails prevent peptide hydrolysis and proteolysis in circulation, and PA monomers are internalized via endocytosis. However, endocytotic sequestration and steric hindrance from the lipid tail are two major mechanisms that limit PA efficacy to target intracellular PPIs. To address these problems, we have constructed a PA platform consisting of cathepsin-B cleavable PAs in which a selective p53-based inhibitory peptide is cleaved from its lipid tail within endosomes, allowing for intracellular peptide accumulation and extracellular recycling of the lipid moiety. We monitor for cleavage and follow individual PA components in real time using a resonance energy transfer (FRET)-based tracking system. Using this platform, components in real time using a Forster we provide a better understanding and quantification of cellular internalization, trafficking, and endosomal cleavage of PAs and of the ultimate fates of each component.

  16. Amphiphilic chitosan derivatives as carrier agents for rotenone

    Science.gov (United States)

    Kamari, Azlan; Aljafree, Nurul Farhana Ahmad

    2017-08-01

    In the present study, the feasibility of amphiphilic chitosan derivatives, namely oleoyl carboxymethyl chitosan (OCMCs), N,N-dimethylhexadecyl carboxymethyl chitosan (DCMCs) and deoxycholic acid carboxymethyl chitosan (DACMCs) as carrier agents for rotenone in water-insoluble pesticide formulations was investigated. Fourier Transform Infrared (FTIR) Spectrometer, CHN-O Elemental Analyser (CHN-O) and Transmission Electron Microscope (TEM) were used to characterise amphiphilic chitosan derivatives. The critical micelle concentration (CMC) of amphiphilic chitosan derivatives was determined using a Fluorescence Spectrometer. A High Performance Liquid Chromatography (HPLC) was used to determine the ability of OCMCs, DCMCs and DACMCs to load and release rotenone in an in vitro system. Based on TEM analysis, results have shown that amphiphilic chitosan derivatives formed self-assembly and exhibited spherical shape. The CMC values determined for OCMCs, DCMCs and DACMCs were 0.093, 0.098 and 0.468 mg/mL, respectively. The encapsulation efficiency (EE) values for the materials were more than 97.0%, meanwhile the loading capacity (LC) values were greater than 0.90%. OCMCs, DCMCs and DACMCs micelles exhibited an excellent ability to control the release of rotenone, of which 90.0% of rotenone was released within 40 to 52 h. In conclusion, OCMCs, DCMCs and DACMCs possess several key features to act as effective carrier agents for rotenone. Overall, amphiphilic chitosan derivatives produced in this study were successfully increased the solubility of rotenone by 49.0 times higher than free rotenone.

  17. Does applying technology throughout the medication use process improve patient safety with antineoplastics?

    Science.gov (United States)

    Bubalo, Joseph; Warden, Bruce A; Wiegel, Joshua J; Nishida, Tess; Handel, Evelyn; Svoboda, Leanne M; Nguyen, Lam; Edillo, P Neil

    2014-12-01

    Medical errors, in particular medication errors, continue to be a troublesome factor in the delivery of safe and effective patient care. Antineoplastic agents represent a group of medications highly susceptible to medication errors due to their complex regimens and narrow therapeutic indices. As the majority of these medication errors are frequently associated with breakdowns in poorly defined systems, developing technologies and evolving workflows seem to be a logical approach to provide added safeguards against medication errors. This article will review both the pros and cons of today's technologies and their ability to simplify the medication use process, reduce medication errors, improve documentation, improve healthcare costs and increase provider efficiency as relates to the use of antineoplastic therapy throughout the medication use process. Several technologies, mainly computerized provider order entry (CPOE), barcode medication administration (BCMA), smart pumps, electronic medication administration record (eMAR), and telepharmacy, have been well described and proven to reduce medication errors, improve adherence to quality metrics, and/or improve healthcare costs in a broad scope of patients. The utilization of these technologies during antineoplastic therapy is weak at best and lacking for most. Specific to the antineoplastic medication use system, the only technology with data to adequately support a claim of reduced medication errors is CPOE. In addition to the benefits these technologies can provide, it is also important to recognize their potential to induce new types of errors and inefficiencies which can negatively impact patient care. The utilization of technology reduces but does not eliminate the potential for error. The evidence base to support technology in preventing medication errors is limited in general but even more deficient in the realm of antineoplastic therapy. Though CPOE has the best evidence to support its use in the

  18. 77 FR 38297 - Revised Document Posted: NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare...

    Science.gov (United States)

    2012-06-27

    ... removed 15 drugs from the 2012 list because they did not meet the NIOSH definition, were no longer... NIOSH-033-A] Revised Document Posted: NIOSH List of Antineoplastic and Other Hazardous Drugs in... of the following document entitled ``NIOSH List of Antineoplastic and Other Hazardous Drugs in...

  19. Self-assembly of fibronectin mimetic peptide-amphiphile nanofibers

    Science.gov (United States)

    Rexeisen, Emilie Lynn

    Many therapeutic strategies incorporate peptides into their designs to mimic the natural protein ligands found in vivo. A few examples are the short peptide sequences RGD and PHSRN that mimic the primary and synergy-binding domains of the extracellular matrix protein, fibronectin, which is recognized by the cell surface receptor, alpha5beta 1 integrin. Even though scaffold modification with biomimetic peptides remains one of the most promising approaches for tissue engineering, the use of these peptides in therapeutic tissue-engineered products and drug delivery systems available on the commercial market is limited because the peptides are not easily able to mimic the natural protein. The design of a peptide that can effectively target the alpha5beta1 integrin would greatly increase biomimetic scaffold therapeutic potential. A novel peptide containing both the RGD primary binding domain and PHSRN synergy-binding domain for fibronectin joined with the appropriate linker should bind alpha 5beta1 integrin more efficiently and lead to greater cell adhesion over RGD alone. Several fibronectin mimetic peptides were designed and coupled to dialkyl hydrocarbon tails to make peptide-amphiphiles. The peptides contained different linkers connecting the two binding domains and different spacers separating the hydrophobic tails from the hydrophilic headgroups. The peptide-amphiphiles were deposited on mica substrates using the Langmuir-Blodgett technique. Langmuir isotherms indicated that the peptide-amphiphiles that contained higher numbers of serine residues formed a more tightly packed monolayer, but the increased number of serines also made transferring the amphiphiles to the mica substrate more difficult. Atomic force microscopy (AFM) images of the bilayers showed that the headgroups might be bent, forming small divots in the surface. These divots may help expose the PHSRN synergy-binding domain. Parallel studies undertaken by fellow group members showed that human

  20. Glucose-neopentyl glycol (GNG) amphiphiles for membrane protein study.

    Science.gov (United States)

    Chae, Pil Seok; Rana, Rohini R; Gotfryd, Kamil; Rasmussen, Søren G F; Kruse, Andrew C; Cho, Kyung Ho; Capaldi, Stefano; Carlsson, Emil; Kobilka, Brian; Loland, Claus J; Gether, Ulrik; Banerjee, Surajit; Byrne, Bernadette; Lee, John K; Gellman, Samuel H

    2013-03-21

    The development of a new class of surfactants for membrane protein manipulation, "GNG amphiphiles", is reported. These amphiphiles display promising behavior for membrane proteins, as demonstrated recently by the high resolution structure of a sodium-pumping pyrophosphatase reported by Kellosalo et al. (Science, 2012, 337, 473).

  1. Competitive Binding of Natural Amphiphiles with Graphene Derivatives

    Science.gov (United States)

    Radic, Slaven; Geitner, Nicholas K.; Podila, Ramakrishna; Käkinen, Aleksandr; Chen, Pengyu; Ke, Pu Chun; Ding, Feng

    2013-01-01

    Understanding the transformation of graphene derivatives by natural amphiphiles is essential for elucidating the biological and environmental implications of this emerging class of engineered nanomaterials. Using rapid discrete-molecular-dynamics simulations, we examined the binding of graphene and graphene oxide with peptides, fatty acids, and cellulose, and complemented our simulations by experimental studies of Raman spectroscopy, FTIR, and UV-Vis spectrophotometry. Specifically, we established a connection between the differential binding and the conformational flexibility, molecular geometry, and hydrocarbon content of the amphiphiles. Importantly, our dynamics simulations revealed a Vroman-like competitive binding of the amphiphiles for the graphene oxide substrate. This study provides a mechanistic basis for addressing the transformation, evolution, transport, biocompatibility, and toxicity of graphene derivatives in living systems and the natural environment. PMID:23881402

  2. Association between occupational exposure levels of antineoplastic drugs and work environment in five hospitals in Japan.

    Science.gov (United States)

    Yoshida, Jin; Koda, Shigeki; Nishida, Shozo; Yoshida, Toshiaki; Miyajima, Keiko; Kumagai, Shinji

    2011-03-01

    The aim of the present study was to evaluate the measurement of contamination by antineoplastic drugs for safer handling of such drugs by medical workers. We investigated the relationship between the contamination level of antineoplastic drugs and the conditions of their handling. Air samples and wipe samples were collected from equipment in the preparation rooms of five hospitals (hospitals A-E). These samples were subjected to measurement of the amounts of cyclophosphamide (CPA), fluorouracil (5FU), gemcitabine (GEM), and platinum-containing drugs (Pt). Twenty-four-hour urine samples were collected from the pharmacists who handled or audited, the antineoplastic drugs were analyzed for CPA and Pt. Pt was detected from air samples inside BSC in hospital B. Antineoplastic drugs were detected from wipe samples of the BSC in hospitals A, B, D, and E and of other equipment in the preparation rooms in hospitals A, B, C, and D. Cyclophosphamide and 5FU were detected from wipe samples of the air-conditioner filter in hospital A, and CPA was detected from that in hospital D. Cyclophosphamide was detected from urine samples of workers in hospitals B, D, and E. The contamination level of antineoplastic drugs was suggested to be related with the amount of drugs handled, cleaning methods of the equipment, and the skill level of the technique of maintaining negative pressure inside a vial. In order to reduce the contamination and exposure to antineoplastic drugs in the hospital work environment very close to zero, comprehensive safety precautions, including adequate mixing and cleaning methods was required in addition to BSC and closed system device.

  3. The rational design of biomimetic skin barrier lipid formulations using biophysical methods.

    Science.gov (United States)

    Bulsara, P A; Varlashkin, P; Dickens, J; Moore, D J; Rawlings, A V; Clarke, M J

    2017-04-01

    The focus of this communication was to study phospholipid-structured emulsions whose phase behaviour is modified with monoalkyl fatty amphiphiles. Ideally, these systems would mimic key physical and structural attributes observed in human stratum corneum (SC) so that they better alleviate xerotic skin conditions. Phosphatidylcholine-structured emulsions were prepared, and their phase behaviour modified with monoalkyl fatty amphiphiles. The effect of molecular volume, acyl chain length and head-group interactions was studied using a combination of physical methods. Water vapour transmission rate (WVTR) was used as a primary test to assess occlusive character. Changes in the vibrational modes observed in Fourier transform infrared (FTIR) spectroscopy and bilayer spacing measured by X-ray diffraction (XRD) were then applied to elucidate the lateral and lamellar microstructural characteristics in the systems. Water vapour transmission rate demonstrated that as the phosphatidylcholine acyl chain length increased from C14, to C18, to C22, there was a corresponding increase in occlusive character. The addition of monoalkyl fatty amphiphiles such as behenic acid, behenyl alcohol or cetostearyl alcohol to a base formulation incorporating dipalmitoyl and distearoylphosphatidylcholine (C18) was seen to further increase barrier characteristics of the emulsions. FTIR methods used to probe lipid-chain conformational ordering demonstrated that as phosphatidylcholine acyl chain lengths increased, there was a corresponding improvement in acyl chain ordering, with an increase in thermal transition temperatures. The addition of a monoalkyl fatty amphiphile resulted in conformational order and thermal transition temperature improvements trending towards those observed in stratum corneum. FTIR also demonstrated that systems containing behenic acid or behenyl alcohol exhibited features associated with orthorhombic character. X-ray diffraction data showed that addition of monoalkyl fatty

  4. Antineoplastic drugs: Occupational exposure and health risks

    OpenAIRE

    Fransman, W.

    2006-01-01

    Antineoplastic drugs are pharmaceuticals commonly used to treat cancer (and some non-neoplastic diseases), which are generally referred to as 'chemotherapy'. Oncology nurses are exposed to these drugs via the skin of hands during daily nursing activities, even when protective gloves are being used. Results of tests on bulk and surface contamination samples confirmed that patients intravenously treated with cyclophosphamide excrete the unmetabolized drug. The introduction of new guidelines and...

  5. Charge-Transfer Supra-Amphiphiles Built by Water-Soluble Tetrathiafulvalenes and Viologen-Containing Amphiphiles: Supramolecular Nanoassemblies with Modifiable Dimensions.

    Science.gov (United States)

    Lv, Zhong-Peng; Chen, Bin; Wang, Hai-Ying; Wu, Yue; Zuo, Jing-Lin

    2015-08-05

    In this study, multidimensional nanoassemblies with various morphologies such as nanosheets, nanorods, and nanofibers are developed via charge-transfer interaction and supra-amphiphile self-assembling in aqueous phase. The charge-transfer interactions between tetrathiafulvalene derivatives (TTFs) and methyl viologen derivatives (MVs) have been confirmed by the characteristic charger-transfer absorption. (1) H NMR and electrospray ionizsation mass spectrometry (ESI-MS) analyses also indicate supra-amphiphiles are formed by the combination of TTFs and MVs head group through charge-transfer interaction and Coulombic force. X-ray single crystal structural studies, transmission electron microscopy (TEM), and scanning electron microscopy (SEM) reveal that both linkage pattern of TTFs in hydrophilic part and alkane chain structure in hydrophobic part have significant influence on nanoassemblies morphology and microstructure. Moreover, gold nanoparticles (AuNPs) are introduced in the above supramolecular nanoassemblies to construct a supra-amphiphile-driven organic-AuNPs assembly system. AuNPs could be assembled into 1D-3D structures by adding different amount of MVs. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Lyotropic liquid crystalline phase behaviour in amphiphile-protic ionic liquid systems.

    Science.gov (United States)

    Chen, Zhengfei; Greaves, Tamar L; Fong, Celesta; Caruso, Rachel A; Drummond, Calum J

    2012-03-21

    Approximate partial phase diagrams for nine amphiphile-protic ionic liquid (PIL) systems have been determined by synchrotron source small angle X-ray scattering, differential scanning calorimetry and cross polarised optical microscopy. The binary phase diagrams of some common cationic (hexadecyltrimethyl ammonium chloride, CTAC, and hexadecylpyridinium bromide, HDPB) and nonionic (polyoxyethylene (10) oleyl ether, Brij 97, and Pluronic block copolymer, P123) amphiphiles with the PILs, ethylammonium nitrate (EAN), ethanolammonium nitrate (EOAN) and diethanolammonium formate (DEOAF), have been studied. The phase diagrams were constructed for concentrations from 10 wt% to 80 wt% amphiphile, in the temperature range 25 °C to >100 °C. Lyotropic liquid crystalline phases (hexagonal, cubic and lamellar) were formed at high surfactant concentrations (typically >50 wt%), whereas at thermal stability of the phases formed by these surfactants persisted to temperatures above 100 °C. The phase behaviour of amphiphile-PIL systems was interpreted by considering the PIL cohesive energy, liquid nanoscale order, polarity and ionicity. For comparison the phase behaviour of the four amphiphiles was also studied in water.

  7. Exploring single chain amphiphile self-assembly and their possible roles in light transduction

    DEFF Research Database (Denmark)

    Monnard, Pierre-Alain

    2011-01-01

    Self-assembled structures of single-chain amphiphiles have been used as hosts for biochemical, and chemical reactions. Their use as models for protocells (i.e., precursors to the first biological cells) has been extensively researched by various groups because the availability of single chain......: the medium composition in terms of ionic strengths and the medium physical parameters, such as temperature, significantly influence the formation of structures, as well as their subsequent stability. In addition, membranes composed of a single amphiphile type seem to be implausible as no potential amphiphile...... source studied to date can supply one single type of amphiphile at concentrations conducive to self-assembly. Mixtures of single-chain amphiphiles were therefore proposed to better model primitive membranes and potentially enhance their structural integrity1-3. Recently, we have established that complex...

  8. Mechanical cell disruption of Parachlorella kessleri microalgae: Impact on lipid fraction composition.

    Science.gov (United States)

    Clavijo Rivera, E; Montalescot, V; Viau, M; Drouin, D; Bourseau, P; Frappart, M; Monteux, C; Couallier, E

    2018-05-01

    Samples of nitrogen-starved Parachlorella kessleri containing intact cells (IC), cells ground by bead milling (BM), and cells subjected to high-pressure cell disruption (HPD), together with their supernatants after centrifugation, were compared for granulometry and lipid profiles. The effects of disruption on the lipid profile and organisation were evaluated. The quantity of lipids available for extraction increased with disruption, and up to 81% could be recovered in supernatants after centrifugation, but a marked reorganization occurred. The proportion of amphiphilic free fatty acids and lysophosphatidylcholine increased during disruption due to their release or owing to lipid degradation by enzymes or physical conditions. This effect was more marked in HPD than in BM. Lipids contained in the aqueous phase, after disruption and centrifugation, were enriched in unsaturated fatty acids, BM leading to larger droplets than HPD. The larger liquid lipid droplet would be easier to recover in the following downstream processing. Copyright © 2018 Elsevier Ltd. All rights reserved.

  9. Hydrophobicity and thermodynamic response for aqueous solutions of amphiphiles

    Science.gov (United States)

    Zemánková, Katerina; Troncoso, Jacobo; Cerdeiriña, Claudio A.; Romaní, Luis; Anisimov, Mikhail A.

    2016-06-01

    The anomalous behavior of aqueous solutions of amphiphiles in the water-rich region is analyzed via a phenomenological approach that utilizes the isobaric heat capacity Cp as an experimental probe. We report extensive data for solutions of 14 amphiphiles as a function of temperature at atmospheric pressure. Beyond that, Cp data but also isobaric thermal expansivities and isothermal compressibilities for three solutions of tert-butanol as a function of both temperature and pressure are presented. Results rule out the possibility that the observed phenomenology is associated with the anomalous thermodynamics of pure water. Indeed, our Cp data, quantitatively consistent with recent spectroscopic analyses, suggest that water-mediated interactions between the nonpolar parts of amphiphiles are at the origin of anomalies, with the effects of such "hydrophobic aggregation" being observed at mole fractions as small as 0.01. Physicochemical details like the size, the electronic charge distribution and the geometry of amphiphile molecules as well as third-order derivatives of the Gibbs energy and the associated Koga lines support the above claims while they further contribute to characterizing the role of hydrophobicity in these phenomena. Progress with a view to gain a deeper, more concrete understanding remains.

  10. Biocompatible Amphiphilic Hydrogel-Solid Dimer Particles as Colloidal Surfactants.

    Science.gov (United States)

    Chen, Dong; Amstad, Esther; Zhao, Chun-Xia; Cai, Liheng; Fan, Jing; Chen, Qiushui; Hai, Mingtan; Koehler, Stephan; Zhang, Huidan; Liang, Fuxin; Yang, Zhenzhong; Weitz, David A

    2017-12-26

    Emulsions of two immiscible liquids can slowly coalesce over time when stabilized by surfactant molecules. Pickering emulsions stabilized by colloidal particles can be much more stable. Here, we fabricate biocompatible amphiphilic dimer particles using a hydrogel, a strongly hydrophilic material, and achieve large contrast in the wetting properties of the two bulbs, resulting in enhanced stabilization of emulsions. We generate monodisperse single emulsions of alginate and shellac solution in oil using a flow-focusing microfluidics device. Shellac precipitates from water and forms a solid bulb at the periphery of the droplet when the emulsion is exposed to acid. Molecular interactions result in amphiphilic dimer particles that consist of two joined bulbs: one hydrogel bulb of alginate in water and the other hydrophobic bulb of shellac. Alginate in the hydrogel compartment can be cross-linked using calcium cations to obtain stable particles. Analogous to surfactant molecules at the interface, the resultant amphiphilic particles stand at the water/oil interface with the hydrogel bulb submerged in water and the hydrophobic bulb in oil and are thus able to stabilize both water-in-oil and oil-in-water emulsions, making these amphiphilic hydrogel-solid particles ideal colloidal surfactants for various applications.

  11. Detection of an amphiphilic biosample in a paper microchannel based on length.

    Science.gov (United States)

    Chen, Yu-Tzu; Yang, Jing-Tang

    2015-01-01

    We developed a simple method to achieve semiquantitative detection of an amphiphilic biosample through measuring the length of flow on a microfluidic analytical device (μPAD) based on paper. When an amphiphilic sample was dripped into a straight microchannel defined with a printed wax barrier (hydrophobic) on filter paper (hydrophilic), the length of flow was affected by the reciprocal effect between the sample, the filter-paper channel and the wax barrier. The flow length decreased with increasing concentration of an amphiphilic sample because of adsorption of the sample on the hydrophobic barrier. Measurement of the flow length enabled a determination of the concentration of the amphiphilic sample. The several tested samples included surfactants (Tween 20 and Triton X-100), oligonucleotides (DNA), bovine serum albumin (BSA), human albumin, nitrite, glucose and low-density lipoprotein (LDL). The results show that the measurement of the flow length determined directly the concentration of an amphiphilic sample, whereas a non-amphiphilic sample was not amenable to this method. The proposed method features the advantages of small cost, simplicity, convenience, directness, rapidity (<5 min) and requirement of only a small volume (5 μL) of sample, with prospective applications in developing areas and sites near patients for testing at a point of care (POCT).

  12. Cationic lipids: molecular structure/ transfection activity relationships and interactions with biomembranes.

    Science.gov (United States)

    Koynova, Rumiana; Tenchov, Boris

    2010-01-01

    Abstract Synthetic cationic lipids, which form complexes (lipoplexes) with polyanionic DNA, are presently the most widely used constituents of nonviral gene carriers. A large number of cationic amphiphiles have been synthesized and tested in transfection studies. However, due to the complexity of the transfection pathway, no general schemes have emerged for correlating the cationic lipid chemistry with their transfection efficacy and the approaches for optimizing their molecular structures are still largely empirical. Here we summarize data on the relationships between transfection activity and cationic lipid molecular structure and demonstrate that the transfection activity depends in a systematic way on the lipid hydrocarbon chain structure. A number of examples, including a large series of cationic phosphatidylcholine derivatives, show that optimum transfection is displayed by lipids with chain length of approximately 14 carbon atoms and that the transfection efficiency strongly increases with increase of chain unsaturation, specifically upon replacement of saturated with monounsaturated chains.

  13. Bola-amphiphile self-assembly

    DEFF Research Database (Denmark)

    Svaneborg, Carsten

    2012-01-01

    Bola-amphiphiles are rod-like molecules where both ends of the molecule likes contact with water, while the central part of the molecule dislikes contact with water. What do such molecules do when they are dissolved in water? They self-assemble into micelles. This is a Dissipartive particle...... dynamics simulation of this self-assembly behaviour....

  14. Reproductive Health Risks Associated with Occupational Exposures to Antineoplastic Drugs in Health Care Settings: A Review of the Evidence

    Science.gov (United States)

    Connor, Thomas H.; Lawson, Christina C.; Polovich, Martha; McDiarmid, Melissa A.

    2015-01-01

    Objectives Antineoplastic drugs are known reproductive and developmental toxicants. Our objective was to review the existing literature of reproductive health risks to workers who handle antineoplastic drugs. Methods A structured literature review of 18 peer-reviewed, English language publications of occupational exposure and reproductive outcomes was performed. Results While effect sizes varied with study size and population, occupational exposure to antineoplastic drugs appears to raise the risk of both congenital malformations and miscarriage. Studies of infertility and time-to-pregnancy also suggested an increased risk for sub-fertility. Conclusions Antineoplastic drugs are highly toxic in patients receiving treatment and adverse reproductive effects have been well documented in these patients. Healthcare workers with chronic, low level occupational exposure to these drugs also appear to have an increased risk of adverse reproductive outcomes. Additional precautions to prevent exposure should be considered. PMID:25153300

  15. Trapping of polycyclic aromatic hydrocarbons by amphiphilic cyclodextrin functionalized polypropylene nonwovens

    DEFF Research Database (Denmark)

    Lumholdt, Ludmilla; Nielsen, Ronnie Bo Højstrup; Larsen, Kim Lambertsen

    of the textile fibers. In this study we present the ability of amphiphilic CD coated polypropylene nonwovens to trap 8 different polycyclic aromatic hydrocarbons/endocrine disruptors from aqueous solutions thus demonstrating the potential of using the amphiphilic cyclodextrins for water purification....

  16. Preparation and Characterization of Amphiphilic Triblock Terpolymer-Based Nanofibers as Antifouling Biomaterials

    KAUST Repository

    Cho, Youngjin; Cho, Daehwan; Park, Jay Hoon; Frey, Margaret W.; Ober, Christopher K.; Joo, Yong Lak

    2012-01-01

    as KB) and fabricated amphiphilic nanofibers by electrospinning of solutions prepared by mixing the KB with poly(lactic acid) (PLA) polymer. The resulting fibers with amphiphilic polymer groups exhibited superior antifouling performance to the fibers

  17. Stimuli Responsive Amphiphilic Assemblies

    Science.gov (United States)

    2013-11-18

    Enzyme- Sensitive, Amphiphilic- Dendrimer -Based Nanoparticles through Photochemical Crosslinking, Chemistry - A European Journal, (10 2011): 0. doi...17, 2012 (Organizers: R. P. Singh) 8th International Dendrimer Symposium (IDS-8), Madrid, Spain, June 23-27, 2013 (Organizers: Dr. M’Angeles...investigate the pH-induced changes in surface properties. Nanocarriers that can be effectively transported across cellular membranes have potential in a

  18. Interfacial Tension and Surface Pressure of High Density Lipoprotein, Low Density Lipoprotein, and Related Lipid Droplets

    DEFF Research Database (Denmark)

    Ollila, O. H. S.; Lamberg, A.; Lehtivaara, M.

    2012-01-01

    ) are essentially lipid droplets surrounded by specific proteins, their main function being to transport cholesterol. Interfacial tension and surface pressure of these particles are of great interest because they are related to the shape and the stability of the droplets and to protein adsorption at the interface....... Here we use coarse-grained molecular-dynamics simulations to consider a number of related issues by calculating the interfacial tension in protein-free lipid droplets, and in HDL and LDL particles mimicking physiological conditions. First, our results suggest that the curvature dependence......Lipid droplets play a central role in energy storage and metabolism on a cellular scale. Their core is comprised of hydrophobic lipids covered by a surface region consisting of amphiphilic lipids and proteins. For example, high and low density lipoproteins (HDL and LDL, respectively...

  19. Tuning Amphiphilicity of Particles for Controllable Pickering Emulsion

    Directory of Open Access Journals (Sweden)

    Zhen Wang

    2016-11-01

    Full Text Available Pickering emulsions with the use of particles as emulsifiers have been extensively used in scientific research and industrial production due to their edge in biocompatibility and stability compared with traditional emulsions. The control over Pickering emulsion stability and type plays a significant role in these applications. Among the present methods to build controllable Pickering emulsions, tuning the amphiphilicity of particles is comparatively effective and has attracted enormous attention. In this review, we highlight some recent advances in tuning the amphiphilicity of particles for controlling the stability and type of Pickering emulsions. The amphiphilicity of three types of particles including rigid particles, soft particles, and Janus particles are tailored by means of different mechanisms and discussed here in detail. The stabilization-destabilization interconversion and phase inversion of Pickering emulsions have been successfully achieved by changing the surface properties of these particles. This article provides a comprehensive review of controllable Pickering emulsions, which is expected to stimulate inspiration for designing and preparing novel Pickering emulsions, and ultimately directing the preparation of functional materials.

  20. Effects of perfluorinated amphiphiles on backward swimming in Paramecium caudatum

    International Nuclear Information System (INIS)

    Matsubara, Eriko; Harada, Kouji; Inoue, Kayoko; Koizumi, Akio

    2006-01-01

    PFOS and PFOA are ubiquitous contaminants in the environment. We investigated the effects of fluorochemicals on calcium currents in Paramecium caudatum using its behavioral changes. Negatively charged amphiphiles prolonged backward swimming (BWS) of Paramecium. PFOS significantly prolonged BWS, while PFOA was less potent (EC 5 : 29.8 ± 4.1 and 424.1 ± 124.0 μM, respectively). The BWS prolongation was blocked by cadmium, indicating that the cellular calcium conductance had been modified. The positively charged amphiphile FOSAPrTMA shortened BWS (EC 5 : 19.1 ± 17.3). Nonionic amphiphiles did not affect BWS. The longer-chain perfluorinated carboxylates PFNA and PFDA were more potent than PFOA (EC 5 : 98.7 ± 20.1 and 60.4 ± 10.1 μM, respectively). However, 1,8-perfluorooctanedioic acid and 1,10-perfluorodecanedioic acid did not prolong BWS. The critical micelle concentration (CMC) and BWS prolongation for negatively charged amphiphiles showed a clear correlation (r 2 = 0.8008, p < 0.001). In summary, several perfluorochemicals and PFOS and PFOA had similar effects in Paramecium, while chain length, CMC, and electric charge were major determinants of BWS duration

  1. Hemifluorinated maltose-neopentyl glycol (HF-MNG) amphiphiles for membrane protein stabilisation.

    Science.gov (United States)

    Cho, Kyung Ho; Byrne, Bernadette; Chae, Pil Seok

    2013-03-04

    SOAP OPERA: Fluorinated amphiphile F4-MNG confers greater stability on Rhodobacter capsulatus superassembly relative to conventional detergents and nonfluorinated MNGs. Such amphiphiles are attractive as tools for membrane science because of their ease of preparation and structure variation. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Stable Vesicles Composed of Mono- or Dicarboxylic Fatty Acids and Trimethylammonium Amphiphiles

    DEFF Research Database (Denmark)

    Caschera, Filippo; Bernardino de la Serna, Jorge; Löffler, Philipp M. G.

    2011-01-01

    shown to be more stable than those formed by pure fatty acids. Those containing bola-amphiphile even showed encapsulation of a small hydrophilic solute (8-hydroxypyrene-1,3,6-trisulfonic-acid) suggesting a denser packing of the amphiphiles. Compression and kinetics analysis of monolayers composed...... of these amphiphiles mixtures at the air/water interface suggest that the stabilization of the structures can be attributed to two main interactions between headgroups, predominantly the formation of hydrogen bonds between protonated and deprotonated acids and then the additional electrostatic interactions between...

  3. A New Class of Amphiphiles Bearing Rigid Hydrophobic Groups for Solubilization and Stabilization of Membrane Proteins

    DEFF Research Database (Denmark)

    Chae, Pil Seok; Rasmussen, Søren G F; Rana, Rohini R

    2012-01-01

    Non-traditional amphiphiles: Conferring aqueous solubility on membrane proteins generally requires the use of a detergent or other amphiphilic agent. A new class of amphiphiles was synthesized, based on steroidal lipophilic groups, and evaluated with several membrane proteins. The results show th...... that the new amphiphile, "glyco-diosgenin" (GDN; see figure), confers enhanced stability to a variety of membrane proteins in solution relative to popular conventional detergents, such as dodecylmaltoside (DDM)....

  4. Dental root agenesis following radiation and antineoplastic therapy: A Case Report

    Directory of Open Access Journals (Sweden)

    Abdul Hafiz

    2016-01-01

    Full Text Available The survival rates of patients suffering from various childhood neoplasms have improved dramatically with the advent of chemo-radiation therapy. The harmful effects of chemo-radiation therapy in the oro-facial region such as root agenesis, short roots, impaired amelogenesis, dentinogenesis, radiation caries, and other soft tissue pathologies are well recognized. In spite of these documented risks, the antineoplastic treatment modalities continue to serve the patient for overall improvement in survival and quality of life. However, a thorough understanding of the growth and development process and its relation with the complex antineoplastic treatment is very important for all clinicians. Such awareness could significantly improve the status of patients in the posttreatment period with the implementation of proper preventive and interceptive measures. This article intends to document a case of root agenesis that developed secondary to chemo-radiation therapy in a 12-year-old girl.

  5. Applications of lipid nanocarriers for solid tumors therapy: literature review

    International Nuclear Information System (INIS)

    Oliveira, Lidiane Correia de; Souza, Leonardo Gomes; Marreto, Ricardo Neves; Lima, Eliana Martins; Taveira, Stephania Fleury; Taveira, Eliseu Jose Fleury

    2012-01-01

    Introduction: Lipid nanocarriers are systems used to target drugs to its site of action and have attracted attention of the scientific community because they are biocompatible and biodegradable. These systems can target drugs to solid tumors, providing sustained drug release in the site of action, thus increasing the utility of the antineoplastic chemotherapy. Objective: To review the available literature on in vivo experiments with lipid nanocarriers containing cytotoxic drugs for solid tumors treatment. Method: A search study was carried out in Pubmed R database from 2007 to 2011, with subject descriptors: liposomes, lipid nanoparticles, cancer and in vivo, with the boolean operator 'and' among them, in English. Results: 1,595 papers related to the use of liposomes and 77 related to lipid nanoparticles were found. Few studies reported in vivo experiments with lipid nanoparticles (28 papers) compared to liposomes (472 papers), since liposomes were developed two decades before lipid nanoparticles. Four liposomal medicines have already been approved and are used in the clinic while only one medicine containing lipid nanoparticles is in phase I of clinical studies. Conclusion: The number of papers related to the use of nanotechnology for cancer treatment is increasing rapidly, making important to know the different kinds of nanocarriers and, especially, those which are already used in the clinic. There are only few clinical studies on lipid nanocarriers; however, these systems present an enormous potential to improve the clinical practice in oncology. (author)

  6. Amphiphilic polymer based on fluoroalkyl and PEG side chains for fouling release coating

    Science.gov (United States)

    Cong, W. W.; Wang, K.; Yu, X. Y.; Zhang, H. Q.; Lv, Z.; Gui, T. J.

    2017-12-01

    Under static conditions, fouling release coating could not express good release property to marine organisms. Amphiphilic polymer with mixture of fluorinated monomer and short side group of polyethylene glycol (PEG) was synthesized. And also we studied the ability of amphiphilic polymer to influence the surface properties and how it controlled the adhesion of marine organisms to coated surfaces. By incorporating fluorinated monomer and PEG side chain into the polymer, the effect of incorporating both polar and non-polar groups on fouling-release coating could be studied. The dry surface was characterized by three-dimensional digital microscopy and scanning electron microscopy (SEM), and the morphology of the amphiphilic fouling release coating showed just like flaky petal. The amphiphilic polymer in fouling release coating tended to reconstruct in water, and the ability was examined by static contact angle, which was smaller than the PDMS (polydimethylsiloxane) fouling release coating. Also surface energy was calculated by three solvents, and surface energy of amphiphilic fouling release coating was higher than that of the PDMS fouling release coating. To understand more about its fouling release property, seawater exposure method was adopted in gulf of Qingdao port. Fewer diatoms Navicula were found in biofilm after using amphiphilic fouling release coating. In general, coating containing both PEG and fluorinated side chain possessed certain fouling release property.

  7. Toxicity classification and evaluation of four pharmaceuticals classes: antibiotics, antineoplastics, cardiovascular, and sex hormones

    International Nuclear Information System (INIS)

    Sanderson, Hans; Brain, Richard A.; Johnson, David J.; Wilson, Christian J.; Solomon, Keith R.

    2004-01-01

    Four different classes of environmental concern are quantitatively and qualitatively assessed for environmental hazards; antibiotics (n = 226), antineoplastics (n = 81), cardiovascular (n = 272), and sex hormones (n 92). These along with an ECOSAR scan of all pharmaceuticals (n = 2848) were then classified according to the OECD aquatic toxicity classification system. The predicted species susceptibility is: daphnid > fish > algae, and the predicted rank order of relative toxicity: sex hormones > cardiovascular antibiotics > antineoplastics (Table 1). Generally, a relatively large proportion (1/3) of all pharmaceuticals are potentially very toxic to aquatic organisms (Table 2). The qualitative risk assessment ranking relative to probability and potential severity for human and environmental health effects is: antibiotics > sex hormones > cardiovascular > antineoplastics. (Q)SARs and pharmacodynamic information should be used to prioritize and steer experimental risk assessments of pharmaceuticals, and potentially, also be used in new drug discovery optimizing efficacy and in minimising environmental hazards of new products. Nuclear receptors are relatively well conserved in evolution. Currently, antibacterial resistance represents the most significant human health hazard, and potentially the largest non-target organism hazard is sex hormones acting as endocrine modulators in wildlife. Data for the individual compounds are accessible via http://www.uoguelph.ca/~hsander/

  8. Controllable Self-Assembly of Amphiphilic Zwitterionic PBI Towards Tunable Surface Wettability of the Nanostructures.

    Science.gov (United States)

    Ye, Yong; Lü, Baozhong; Cheng, Wenyu; Wu, Zhen; Wei, Jie; Yin, Meizhen

    2017-05-04

    Amphiphilic molecules have received wide attention as they possess both hydrophobic and hydrophilic properties, and can form diverse nanostructures in selective solvents. Herein, we report an asymmetric amphiphilic zwitterionic perylene bisimide (AZP) with an octyl chain and a zwitterionic group on the opposite imide positions of perylene tetracarboxylic dianhydride. The controllable nanostructures of AZP with tunable hydrophilic/hydrophobic surface have been investigated through solvent-dependent amphiphilic self-assembly as confirmed by SEM, TEM, and contact angle measurements. The planar perylene core of AZP contributes to strong π-π stacking, while the amphiphilic balance of asymmetric AZP adjusts the self-assembly property. Additionally, due to intermolecular π-π stacking and solvent-solute interactions, AZP could self-assemble into hydrophilic microtubes in a polar solvent (acetone) and hydrophobic nanofibers in an apolar solvent (hexane). This facile method provides a new pathway for controlling the surface properties based on an asymmetric amphiphilic zwitterionic perylene bisimide. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Lipid Bilayer – mediated Regulation of Ion Channel Function by Amphiphilic Drugs

    DEFF Research Database (Denmark)

    Lundbæk, Jens August

    2008-01-01

    that are transforming it into a subject of quantitative science. It is described how the hydrophobic interactions between a membrane protein and the host lipid bilayer provide the basis for a mechanism, whereby protein function is regulated by the bilayer physical properties. The use of gramicidin channels as single-molecule......Drugs that at pico- to nanomolar concentration regulate ion channel function by high-affi nity binding to their cognate receptor often have a “ secondary pharmacology, ” in which the same molecule at low micromolar concentrations regulates a diversity of membrane proteins in an apparently...... nonspecifi c manner. It has long been suspected that this promiscuous regulation of membrane protein function could be due to changes in the physical properties of the host lipid bilayer, but the underlying mechanisms have been poorly understood. Given that pharmacological research often involves drug...

  10. Magnetic Amphiphilic Composites Applied for the Treatment of Biodiesel Wastewaters

    Directory of Open Access Journals (Sweden)

    Bruno R. S. Lemos

    2012-05-01

    Full Text Available In this work, new magnetic amphiphilic composites were prepared by chemical vapor deposition with ethanol on the surface of hydrophilic natural chrysotile matrix containing Fe catalyst. XRD, Raman, Mössbauer and SEM analyses suggest the formation of a complex nanostructured material composed of hydrophobic carbon nanotubes/nanofibers grown on the hydrophilic surface of the MgSi fiber mineral and the presence of Fe metallic nanoparticles coated by carbon. These nanostructured particles show amphiphilic properties and interact very well with both oil and aqueous phases. When added to emulsions the amphiphilic particles locate on the oil/water interface and, under a magnetic field, the oil droplets collapsed leading to the separation of the aqueous and oil phases. Preliminary work showed excellent results on the use of these particles to break wastewater emulsions in the biodiesel process.

  11. Synthesis and characterization of maltose-based amphiphiles as supramolecular hydrogelators.

    Science.gov (United States)

    Clemente, María J; Fitremann, Juliette; Mauzac, Monique; Serrano, José L; Oriol, Luis

    2011-12-20

    Low molecular mass amphiphilic glycolipids have been prepared by linking a maltose polar head and a hydrophobic linear chain either by amidation or copper(I)-catalyzed azide-alkyne [3 + 2] cycloaddition. The liquid crystalline properties of these amphiphilic materials have been characterized. The influence of the chemical structure of these glycolipids on the gelation properties in water has also been studied. Glycolipids obtained by the click coupling of the two components give rise to stable hydrogels at room temperature. The fibrillar structure of supramolecular hydrogels obtained by the self-assembly of these gelators have been characterized by electron microscopy. Fibers showed some torsion, which could be related with a chiral supramolecular arrangement of amphiphiles, as confirmed by circular dichroism (CD). The sol-gel transition temperature was also determined by differential scanning calorimetry (DSC) and NMR. © 2011 American Chemical Society

  12. Plant lipid environment and membrane enzymes: the case of the plasma membrane H+-ATPase.

    Science.gov (United States)

    Morales-Cedillo, Francisco; González-Solís, Ariadna; Gutiérrez-Angoa, Lizbeth; Cano-Ramírez, Dora Luz; Gavilanes-Ruiz, Marina

    2015-04-01

    Several lipid classes constitute the universal matrix of the biological membranes. With their amphipathic nature, lipids not only build the continuous barrier that confers identity to every cell and organelle, but they are also active actors that modulate the activity of the proteins immersed in the lipid bilayer. The plasma membrane H(+)-ATPase, an enzyme from plant cells, is an excellent example of a transmembrane protein whose activity is influenced by the hydrophilic compartments at both sides of the membrane and by the hydrophobic domains of the lipid bilayer. As a result, an extensive documentation of the effect of numerous amphiphiles in the enzyme activity can be found. Detergents, membrane glycerolipids, and sterols can produce activation or inhibition of the enzyme activity. In some cases, these effects are associated with the lipids of the membrane bulk, but in others, a direct interaction of the lipid with the protein is involved. This review gives an account of reports related to the action of the membrane lipids on the H(+)-ATPase activity.

  13. Regulation of membrane protein function by lipid bilayer elasticity-a single molecule technology to measure the bilayer properties experienced by an embedded protein

    International Nuclear Information System (INIS)

    Lundbaek, Jens August

    2006-01-01

    Membrane protein function is generally regulated by the molecular composition of the host lipid bilayer. The underlying mechanisms have long remained enigmatic. Some cases involve specific molecular interactions, but very often lipids and other amphiphiles, which are adsorbed to lipid bilayers, regulate a number of structurally unrelated proteins in an apparently non-specific manner. It is well known that changes in the physical properties of a lipid bilayer (e.g., thickness or monolayer spontaneous curvature) can affect the function of an embedded protein. However, the role of such changes, in the general regulation of membrane protein function, is unclear. This is to a large extent due to lack of a generally accepted framework in which to understand the many observations. The present review summarizes studies which have demonstrated that the hydrophobic interactions between a membrane protein and the host lipid bilayer provide an energetic coupling, whereby protein function can be regulated by the bilayer elasticity. The feasibility of this 'hydrophobic coupling mechanism' has been demonstrated using the gramicidin channel, a model membrane protein, in planar lipid bilayers. Using voltage-dependent sodium channels, N-type calcium channels and GABA A receptors, it has been shown that membrane protein function in living cells can be regulated by amphiphile induced changes in bilayer elasticity. Using the gramicidin channel as a molecular force transducer, a nanotechnology to measure the elastic properties experienced by an embedded protein has been developed. A theoretical and technological framework, to study the regulation of membrane protein function by lipid bilayer elasticity, has been established

  14. Asymmetric and symmetric bolaform supra-amphiphiles: formation of imine bond influenced by aggregation.

    Science.gov (United States)

    Wang, Guangtong; Wu, Guanglu; Wang, Zhiqiang; Zhang, Xi

    2014-02-18

    A series of bolaform supra-amphilphiles with different symmetries were fabricated through dynamic benzoic imine bond formation. The pH dependence of imine formations of these supra-amphiphiles were characterazied. We found that the extent of the imine formation of these supra-amphiphies were different. The supra-amphiphiles with a poorer symmetry always exhibited a lower imine formation at a given pH. Therefore, the varied extent of imine bond formation indicate the different aggregations of these supra-amphilphiles, which are controlled by the molecular symmetry of the supra-amphiphiles.

  15. Anti-Biofouling Properties of Comblike Block Copolymers with Amphiphilic Side Chains

    International Nuclear Information System (INIS)

    Krishnan, S.; Ayothi, R.; Hexemer, A.; Finlay, J.; Sohn, K.; Perry, R.; Ober, C.; Kramer, E.; Callow, M.

    2006-01-01

    Surfaces of novel block copolymers with amphiphilic side chains were studied for their ability to influence the adhesion of marine organisms. The surface-active polymer, obtained by grafting fluorinated molecules with hydrophobic and hydrophilic blocks to a block copolymer precursor, showed interesting bioadhesion properties. Two different algal species, one of which adhered strongly to hydrophobic surfaces, and the other, to hydrophilic surfaces, showed notably weak adhesion to the amphiphilic surfaces. Both organisms are known to secrete adhesive macromolecules, with apparently different wetting characteristics, to attach to underwater surfaces. The ability of the amphiphilic surface to undergo an environment-dependent transformation in surface chemistry when in contact with the extracellular polymeric substances is a possible reason for its antifouling nature. Near-edge X-ray absorption fine structure spectroscopy (NEXAFS) was used, in a new approach based on angle-resolved X-ray photoelectron spectroscopy (XPS), to determine the variation in chemical composition within the top few nanometers of the surface and also to study the surface segregation of the amphiphilic block. A mathematical model to extract depth-profile information from the normalized NEXAFS partial electron yield is developed

  16. Fabrication of novel biodegradable porous bone scaffolds based on amphiphilic hydroxyapatite nanorods

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Xiaoyan; Hui, Junfeng [Shaanxi Key Laboratory of Degradable Biomedical Materials, Shaanxi R& D Center of Biomaterials and Fermentation Engineering, School of Chemical and Engineering, Northwest University, Xi' an 710069, Shaanxi, PR China2 (China); Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of the Ministry of Education, Shaanxi Key Laboratory of Physico-Inorganic Chemistry, College of Chemistry & Materials Science, Northwest University, Xi' an 710069, Shaanxi (China); Li, Hui; Zhu, Chenhui [Shaanxi Key Laboratory of Degradable Biomedical Materials, Shaanxi R& D Center of Biomaterials and Fermentation Engineering, School of Chemical and Engineering, Northwest University, Xi' an 710069, Shaanxi, PR China2 (China); Hua, Xiufu, E-mail: hua_xiufu@163.com [Department of Scientific Research and Development, Tsinghua University, Beijing 100084 (China); Ma, Haixia, E-mail: mahx@nwu.edu.cn [Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of the Ministry of Education, Shaanxi Key Laboratory of Physico-Inorganic Chemistry, College of Chemistry & Materials Science, Northwest University, Xi' an 710069, Shaanxi (China); Fan, Daidi, E-mail: fandaidi@nwu.edu.cn [Shaanxi Key Laboratory of Degradable Biomedical Materials, Shaanxi R& D Center of Biomaterials and Fermentation Engineering, School of Chemical and Engineering, Northwest University, Xi' an 710069, Shaanxi, PR China2 (China)

    2017-06-01

    This paper describes a new synthetic strategy and biological application for novel amphiphilic hydroxyapatite (HAp) nanorods. The prepared HAp nanorods were able to be dispersed in water, ethyl alcohol and cyclohexane. The co-anchoring of the multidentate ligands of PEG 20000 and hydrophobic oleic acid (OA) on the rods' surfaces endowed them with excellent amphibious properties. Utilizing amphiphilic HAp nanorods with excellent biocompatibility as the inorganic phase, human-like collagen (HLC) as the organic phase and natural genipin as the cross-linker, optimal HLC/HAp porous scaffolds (HLC: HAp = 1:4, w/w) were fabricated. The compression stress and three-point bending strength of the scaffolds with pore diameters of 150 to 200 μm reached approximately 3.4 MPa and 5.4 MPa, respectively, and their porosity was 77.35 ± 3.75%. Cytological tests showed that HLC/HAp scaffolds could contribute to cell proliferation and differentiation. The results indicated that these novel amphiphilic HAp nanorods can be expected to become recognized as an excellent inorganic material for the porous scaffolds used in repairing bone and related applications. - Highlights: • A simple and effective hydrothermal method was developed for preparing uniform HAp nanorods with amphiphilic surfaces. • The synthesized amphiphilic HAp nanorods could be dispersed in water, ethyl alcohol or cyclohexane. • The prepared HLC/HAp porous scaffolds had good mechanical properties, biocompatibility and osteoconductive etc.

  17. Fabrication of novel biodegradable porous bone scaffolds based on amphiphilic hydroxyapatite nanorods

    International Nuclear Information System (INIS)

    Zheng, Xiaoyan; Hui, Junfeng; Li, Hui; Zhu, Chenhui; Hua, Xiufu; Ma, Haixia; Fan, Daidi

    2017-01-01

    This paper describes a new synthetic strategy and biological application for novel amphiphilic hydroxyapatite (HAp) nanorods. The prepared HAp nanorods were able to be dispersed in water, ethyl alcohol and cyclohexane. The co-anchoring of the multidentate ligands of PEG 20000 and hydrophobic oleic acid (OA) on the rods' surfaces endowed them with excellent amphibious properties. Utilizing amphiphilic HAp nanorods with excellent biocompatibility as the inorganic phase, human-like collagen (HLC) as the organic phase and natural genipin as the cross-linker, optimal HLC/HAp porous scaffolds (HLC: HAp = 1:4, w/w) were fabricated. The compression stress and three-point bending strength of the scaffolds with pore diameters of 150 to 200 μm reached approximately 3.4 MPa and 5.4 MPa, respectively, and their porosity was 77.35 ± 3.75%. Cytological tests showed that HLC/HAp scaffolds could contribute to cell proliferation and differentiation. The results indicated that these novel amphiphilic HAp nanorods can be expected to become recognized as an excellent inorganic material for the porous scaffolds used in repairing bone and related applications. - Highlights: • A simple and effective hydrothermal method was developed for preparing uniform HAp nanorods with amphiphilic surfaces. • The synthesized amphiphilic HAp nanorods could be dispersed in water, ethyl alcohol or cyclohexane. • The prepared HLC/HAp porous scaffolds had good mechanical properties, biocompatibility and osteoconductive etc.

  18. Sacrificial amphiphiles: Eco-friendly chemical herders as oil spill mitigation chemicals.

    Science.gov (United States)

    Gupta, Deeksha; Sarker, Bivas; Thadikaran, Keith; John, Vijay; Maldarelli, Charles; John, George

    2015-06-01

    Crude oil spills are a major threat to marine biota and the environment. When light crude oil spills on water, it forms a thin layer that is difficult to clean by any methods of oil spill response. Under these circumstances, a special type of amphiphile termed as "chemical herder" is sprayed onto the water surrounding the spilled oil. The amphiphile forms a monomolecular layer on the water surface, reducing the air-sea surface tension and causing the oil slick to retract into a thick mass that can be burnt in situ. The current best-known chemical herders are chemically stable and nonbiodegradable, and hence remain in the marine ecosystem for years. We architect an eco-friendly, sacrificial, and effective green herder derived from the plant-based small-molecule phytol, which is abundant in the marine environment, as an alternative to the current chemical herders. Phytol consists of a regularly branched chain of isoprene units that form the hydrophobe of the amphiphile; the chain is esterified to cationic groups to form the polar group. The ester linkage is proximal to an allyl bond in phytol, which facilitates the hydrolysis of the amphiphile after adsorption to the sea surface into the phytol hydrophobic tail, which along with the unhydrolyzed herder, remains on the surface to maintain herding action, and the cationic group, which dissolves into the water column. Eventual degradation of the phytol tail and dilution of the cation make these sacrificial amphiphiles eco-friendly. The herding behavior of phytol-based amphiphiles is evaluated as a function of time, temperature, and water salinity to examine their versatility under different conditions, ranging from ice-cold water to hot water. The green chemical herder retracted oil slicks by up to ~500, 700, and 2500% at 5°, 20°, and 35°C, respectively, during the first 10 min of the experiment, which is on a par with the current best chemical herders in practice.

  19. Phases and phase transition in insoluble and adsorbed monolayers of amide amphiphiles: Specific characteristics of the condensed phases.

    Science.gov (United States)

    Vollhardt, D

    2015-08-01

    For understanding the role of amide containing amphiphiles in inherently complex biological processes, monolayers at the air-water interface are used as simple biomimetic model systems. The specific characteristics of the condensed phases and phase transition in insoluble and adsorbed monolayers of amide amphiphiles are surveyed to highlight the effect of the chemical structure of the amide amphiphiles on the interfacial interactions in model monolayers. The mesoscopic topography and/or two-dimensional lattice structures of selected amino acid amphiphiles, amphiphilic N-alkylaldonamide, amide amphiphiles with specific tailored headgroups, such as amide amphiphiles based on derivatized ethanolamine, e.g. acylethanolamines (NAEs) and N-,O-diacylethanolamines (DAEs) are presented. Special attention is devoted the dominance of N,O-diacylated ethanolamine in mixed amphiphilic acid amide monolayers. The evidence that a first order phase transition can occur in adsorption layers and that condensed phase domains of mesoscopic scale can be formed in adsorption layers was first obtained on the basis of the experimental characteristics of a tailored amide amphiphile. New thermodynamic and kinetic concepts for the theoretical description of the characteristics of amide amphiphile's monolayers were developed. In particular, the equation of state for Langmuir monolayers generalized for the case that one, two or more phase transitions occur, and the new theory for phase transition in adsorbed monolayers are experimentally confirmed at first by amide amphiphile monolayers. Despite the significant progress made towards the understanding the model systems, these model studies are still limited to transfer the gained knowledge to biological systems where the fundamental physical principles are operative in the same way. The study of biomimetic systems, as described in this review, is only a first step in this direction. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Amphiphilic cationic peptides mediate cell adhesion to plastic surfaces.

    Science.gov (United States)

    Rideout, D C; Lambert, M; Kendall, D A; Moe, G R; Osterman, D G; Tao, H P; Weinstein, I B; Kaiser, E T

    1985-09-01

    Four amphiphilic peptides, each with net charges of +2 or more at neutrality and molecular weights under 4 kilodaltons, were found to mediate the adhesion of normal rat kidney fibroblasts to polystyrene surfaces. Two of these peptides, a model for calcitonin (peptide 1, MCT) and melittin (peptide 2, MEL), form amphiphilic alpha-helical structures at aqueous/nonpolar interfaces. The other two, a luteinizing hormone-releasing hormone model (peptide 3, LHM) and a platelet factor model (peptide 4, MPF) form beta-strand structures in amphiphilic environments. Although it contains only 10 residues, LHM mediated adhesion to surfaces coated with solutions containing as little as 10 pmoles/ml of peptide. All four of these peptides were capable of forming monolayers at air-buffer interfaces with collapse pressures greater than 20 dynes/cm. None of these four peptides contains the tetrapeptide sequence Arg-Gly-Asp-Ser, which has been associated with fibronectin-mediated cell adhesion. Ten polypeptides that also lacked the sequence Arg-Gly-Asp-Ser but were nonamphiphilic and/or had net charges less than +2 at neutrality were all incapable of mediating cell adhesion (Pierschbacher and Ruoslahti, 1984). The morphologies of NRK cells spread on polystyrene coated with peptide LHM resemble the morphologies on fibronectin-coated surfaces, whereas cells spread on surfaces coated with MCT or MEL exhibit strikingly different morphologies. The adhesiveness of MCT, MEL, LHM, and MPF implies that many amphiphilic cationic peptides could prove useful as well defined adhesive substrata for cell culture and for studies of the mechanism of cell adhesion.

  1. Lipid flopping in the liver.

    Science.gov (United States)

    Linton, Kenneth J

    2015-10-01

    Bile is synthesized in the liver and is essential for the emulsification of dietary lipids and lipid-soluble vitamins. It is a complex mixture of amphiphilic bile acids (BAs; which act as detergent molecules), the membrane phospholipid phosphatidylcholine (PC), cholesterol and a variety of endogenous metabolites and waste products. Over the last 20 years, the combined effort of clinicians, geneticists, physiologists and biochemists has shown that each of these bile components is transported across the canalicular membrane of the hepatocyte by its own specific ATP-binding cassette (ABC) transporter. The bile salt export pump (BSEP) ABCB11 transports the BAs and drives bile flow from the liver, but it is now clear that two lipid transporters, ABCB4 (which flops PC into the bile) and the P-type ATPase ATP8B1/CDC50 (which flips a different phospholipid in the opposite direction) play equally critical roles that protect the biliary tree from the detergent activity of the bile acids. Understanding the interdependency of these lipid floppases and flippases has allowed the development of an assay to measure ABCB4 function. ABCB4 harbours numerous mis-sense mutations which probably reflects the spectrum of liver disease rooted in ABCB4 aetiology. Characterization of the effect of these mutations at the protein level opens the possibility for the development of personalized prognosis and treatment. © 2015 Authors; published by Portland Press Limited.

  2. Self-assembly of a triangle-shaped, hexaplatinum-incorporated, supramolecular amphiphile in solution and at interfaces.

    Science.gov (United States)

    Maran, Umamageswaran; Britt, David; Fox, Christopher B; Harris, Joel M; Orendt, Anita M; Conley, Hiram; Davis, Robert; Hlady, Vladamir; Stang, Peter J

    2009-08-24

    The self-assembly and characterization of a novel supramolecular amphiphile built from a new 60 degree amphiphilic precursor that incorporates hydrophilic platinum(II) metals and hydrophobic dioctadecyloxy chains is reported. The amphiphilic macrocycle and its precursor compound have been characterized by multinuclear NMR spectroscopy, ESI-MS, and other standard techniques. The coacervate morphology of the amphiphile at the liquid-liquid interface has been studied by using confocal optical microscopy and in situ Raman spectroscopy. The self-assembly of the amphiphilic macrocycle at the air-water interface has been investigated through Langmuir-trough techniques. The study indicates the possible formation of surface micelle-like aggregates. The disparity between the experimental molecular areas and those derived from molecular models support the idea of aggregation. AFM images of the surface aggregates show the formation of a flat topology with arbitrary ridgelike patterns. Reasonable molecular-packing arrangements are proposed to explain the molecular organization within the observed structures.

  3. Maltose-neopentyl glycol (MNG) amphiphiles for solubilization, stabilization and crystallization of membrane proteins

    DEFF Research Database (Denmark)

    Chae, Pil Seok; Rasmussen, Søren G F; Rana, Rohini R

    2010-01-01

    proteins remain difficult to study owing to a lack of suitable detergents. We introduce a class of amphiphiles, each built around a central quaternary carbon atom derived from neopentyl glycol, with hydrophilic groups derived from maltose. Representatives of this maltose-neopentyl glycol (MNG) amphiphile...

  4. Clinical effect of Cystenosine on leukocytopenia at the time of therapy with radiation and antineoplastic agents

    International Nuclear Information System (INIS)

    Sato, Kazuhide; Usui, Ryu; Inoue, Hiroshi; Mihashi, Norio; Niibe, Hideo.

    1977-01-01

    Out of 62 cases, 25 cases received only radiotherapy, 11 cases received both radiotherapy and antineoplastic agents, and 26 cases received only antineoplastic agents. Total dose of x-ray ranges from 3000 to 6200 rad in 18 of 36 cases of the former two groups, and 2600 to 6260 rad of 60 Co dose were irradiated to 18 cases of the rest. This agent was administered 9 tablets per a day (one tablet contains 200 mg of inosine and 20 mg of cystine) for 19 to 142 days. Its effects on leukocytopenia showed marked effectiveness in 9 out of 25 cases treated with only radiation, effectiveness in 8 cases, and ineffectiveness in 3 cases. Its effective rate was 72.8%. The effective rate was 65.4% in the cases treated with only antineoplastic agents, and was 67.7% in all cases. A certain relationship between dose and the effective rate was not recognized. Radiation sickness, such as loss of appetite general fatigue and mausea, decreased gradually by using this agent. Side effect was not recognized particularly. (Kanao. N.)

  5. Amphiphilic copolymers for fouling-release coatings

    DEFF Research Database (Denmark)

    Noguer, Albert Camós; Olsen, Stefan Møller; Hvilsted, Søren

    of the coatings [9,10,11]. This work shows the effect of an amphiphilic copolymer that induces hydrophilicity on the surface of the silicone-based fouling release coatings. The behaviour of these copolymers within the coating upon immersion and the interaction of these surface-active additives with other...

  6. Improved surface property of PVDF membrane with amphiphilic zwitterionic copolymer as membrane additive

    Energy Technology Data Exchange (ETDEWEB)

    Li Jianhua, E-mail: jhli_2005@163.com [Institute of Biomedical and Pharmaceutical Technology and College of Chemistry and Chemical Engineering, Fuzhou University, Fuzhou 350001 (China); Li Mizi; Miao Jing; Wang Jiabin; Shao Xisheng [Institute of Biomedical and Pharmaceutical Technology and College of Chemistry and Chemical Engineering, Fuzhou University, Fuzhou 350001 (China); Zhang Qiqing, E-mail: zhangqiq@126.com [Institute of Biomedical and Pharmaceutical Technology and College of Chemistry and Chemical Engineering, Fuzhou University, Fuzhou 350001 (China) and Institute of Biomedical Engineering, Chinese Academy of Medical Science, Peking Union Medical College, Tianjin 300192 (China)

    2012-06-15

    An attempt to improve hydrophilicity and anti-fouling properties of PVDF membranes, a novel amphiphilic zwitterionic copolymer poly(vinylidene fluoride)-graft-poly(sulfobetaine methacrylate) (PVDF-g-PSBMA) was firstly synthesized by atom transfer radical polymerization (ATRP) and used as amphiphilic copolymer additive in the preparation of PVDF membranes. The PVDF-g-PSBMA/PVDF blend membranes were prepared by immersion precipitation process. Fourier transform infrared attenuated reflection spectroscopy (FTIR-ATR) and X-ray photoelectronic spectroscopy (XPS) measurements confirmed that PSBMA brushes from amphiphilic additives were preferentially segregated to membrane-coagulant interface during membrane formation. The morphology of membranes was characterized by scanning electron microscopy (SEM). Water contact angle measurements showed that the surface hydrophilicity of PVDF membranes was improved significantly with the increasing of amphiphilic copolymer PVDF-g-PSBMA in cast solution. Protein static adsorption experiment and dynamic fouling resistance experiment revealed that the surface enrichment of PSBMA brush endowed PVDF blend membrane great improvement of surface anti-fouling ability.

  7. Improved surface property of PVDF membrane with amphiphilic zwitterionic copolymer as membrane additive

    International Nuclear Information System (INIS)

    Li Jianhua; Li Mizi; Miao Jing; Wang Jiabin; Shao Xisheng; Zhang Qiqing

    2012-01-01

    An attempt to improve hydrophilicity and anti-fouling properties of PVDF membranes, a novel amphiphilic zwitterionic copolymer poly(vinylidene fluoride)-graft-poly(sulfobetaine methacrylate) (PVDF-g-PSBMA) was firstly synthesized by atom transfer radical polymerization (ATRP) and used as amphiphilic copolymer additive in the preparation of PVDF membranes. The PVDF-g-PSBMA/PVDF blend membranes were prepared by immersion precipitation process. Fourier transform infrared attenuated reflection spectroscopy (FTIR-ATR) and X-ray photoelectronic spectroscopy (XPS) measurements confirmed that PSBMA brushes from amphiphilic additives were preferentially segregated to membrane-coagulant interface during membrane formation. The morphology of membranes was characterized by scanning electron microscopy (SEM). Water contact angle measurements showed that the surface hydrophilicity of PVDF membranes was improved significantly with the increasing of amphiphilic copolymer PVDF-g-PSBMA in cast solution. Protein static adsorption experiment and dynamic fouling resistance experiment revealed that the surface enrichment of PSBMA brush endowed PVDF blend membrane great improvement of surface anti-fouling ability.

  8. Effects of organizational safety practices and perceived safety climate on PPE usage, engineering controls, and adverse events involving liquid antineoplastic drugs among nurses.

    Science.gov (United States)

    DeJoy, David M; Smith, Todd D; Woldu, Henok; Dyal, Mari-Amanda; Steege, Andrea L; Boiano, James M

    2017-07-01

    Antineoplastic drugs pose risks to the healthcare workers who handle them. This fact notwithstanding, adherence to safe handling guidelines remains inconsistent and often poor. This study examined the effects of pertinent organizational safety practices and perceived safety climate on the use of personal protective equipment, engineering controls, and adverse events (spill/leak or skin contact) involving liquid antineoplastic drugs. Data for this study came from the 2011 National Institute for Occupational Safety and Health (NIOSH) Health and Safety Practices Survey of Healthcare Workers which included a sample of approximately 1,800 nurses who had administered liquid antineoplastic drugs during the past seven days. Regression modeling was used to examine predictors of personal protective equipment use, engineering controls, and adverse events involving antineoplastic drugs. Approximately 14% of nurses reported experiencing an adverse event while administering antineoplastic drugs during the previous week. Usage of recommended engineering controls and personal protective equipment was quite variable. Usage of both was better in non-profit and government settings, when workers were more familiar with safe handling guidelines, and when perceived management commitment to safety was higher. Usage was poorer in the absence of specific safety handling procedures. The odds of adverse events increased with number of antineoplastic drugs treatments and when antineoplastic drugs were administered more days of the week. The odds of such events were significantly lower when the use of engineering controls and personal protective equipment was greater and when more precautionary measures were in place. Greater levels of management commitment to safety and perceived risk were also related to lower odds of adverse events. These results point to the value of implementing a comprehensive health and safety program that utilizes available hazard controls and effectively communicates

  9. The Lipid A from the Haloalkaliphilic Bacterium Salinivibrio sharmensis Strain BAGT

    Directory of Open Access Journals (Sweden)

    Maria Michela Corsaro

    2013-01-01

    Full Text Available Lipid A is a major constituent of the lipopolysaccharides (or endotoxins, which are complex amphiphilic macromolecules anchored in the outer membrane of Gram-negative bacteria. The glycolipid lipid A is known to possess the minimal chemical structure for LPSs endotoxic activity, able to cause septic shock. Lipid A isolated from extremophiles is interesting, since very few cases of pathogenic bacteria have been found among these microorganisms. In some cases their lipid A has shown to have an antagonist activity, i.e., it is able to interact with the immune system of the host without triggering a proinflammatory response by blocking binding of substances that could elicit such a response. However, the relationship between the structure and the activity of these molecules is far from being completely clear. A deeper knowledge of the lipid A chemical structure can help the understanding of these mechanisms. In this manuscript, we present our work on the complete structural characterization of the lipid A obtained from the lipopolysaccharides (LPS of the haloalkaliphilic bacterium Salinivibrio sharmensis. Lipid A was obtained from the purified LPS by mild acid hydrolysis. The lipid A, which contains different number of fatty acids residues, and its partially deacylated derivatives were completely characterized by means of electrospray ionization Fourier transform ion cyclotron (ESI FT-ICR mass spectrometry and chemical analysis.

  10. Cationic Amphiphiles Increase Activity of Aminoglycoside Antibiotic Tobramycin in the Presence of Airway Polyelectrolytes

    International Nuclear Information System (INIS)

    Purdy Drew, Kirstin R.; Sanders, Lori K.; Culumber, Zachary W.; Zribi, Olena; Wong, Gerard C.L.

    2009-01-01

    It is empirically known that anionic polyelectrolytes present in cystic fibrosis (CF) airways due to bacterial infection significantly decrease the activity of cationic antimicrobials via electrostatic binding. In this work, we use synchrotron small-angle X-ray scattering to investigate the interaction between tobramycin, an aminoglycoside antibiotic commonly administered to CF patients via inhalation, with DNA, which is found in high concentrations in the CF airway. We find that interactions between DNA and tobramycin are significantly modified by the presence of mixtures of amphiphilic molecules. We measure a hierarchy of self-assembled structures formed between tobramycin, DNA, and the amphiphile mixtures and show how interactions between these components can be controlled. Results indicate that mixtures of cationic and negative curvature amphiphiles optimized for DNA binding via charge matching and curvature matching can competitively displace bound tobramycin from DNA and thereby drastically suppress tobramycin-DNA binding and resultant antimicrobial inactivation. Growth inhibition assays confirm the increased activity of tobramycin in the presence of DNA with the addition of the amphiphiles. These results suggest that optimized cationic amphiphile solutions have the potential to enhance antimicrobial function in highly infected environments that contain increased concentrations of anionic inflammatory polymers.

  11. Cationic Amphiphiles Increase Activity of Aminoglycoside Antibiotic Tobramycin in the Presence of Airway Polyelectrolytes

    International Nuclear Information System (INIS)

    Drew, K.R.Purdy; Sanders, L.K.; Culumber, Z.W.; Zribi, O.; Wong, G.C.L.

    2009-01-01

    It is empirically known that anionic polyelectrolytes present in cystic fibrosis (CF) airways due to bacterial infection significantly decrease the activity of cationic antimicrobials via electrostatic binding. In this work, we use synchrotron small-angle X-ray scattering to investigate the interaction between tobramycin, an aminoglycoside antibiotic commonly administered to CF patients via inhalation, with DNA, which is found in high concentrations in the CF airway. We find that interactions between DNA and tobramycin are significantly modified by the presence of mixtures of amphiphilic molecules. We measure a hierarchy of self-assembled structures formed between tobramycin, DNA, and the amphiphile mixtures and show how interactions between these components can be controlled. Results indicate that mixtures of cationic and negative curvature amphiphiles optimized for DNA binding via charge matching and curvature matching can competitively displace bound tobramycin from DNA and thereby drastically suppress tobramycin-DNA binding and resultant antimicrobial inactivation. Growth inhibition assays confirm the increased activity of tobramycin in the presence of DNA with the addition of the amphiphiles. These results suggest that optimized cationic amphiphile solutions have the potential to enhance antimicrobial function in highly infected environments that contain increased concentrations of anionic inflammatory polymers

  12. Changes in the chemical composition of mineralised teeth in children after antineoplastic treatment.

    Science.gov (United States)

    Krasuska-Sławińska, Ewa; Dembowska-Bagińska, Bożenna; Brożyna, Agnieszka; Olczak-Kowalczyk, Dorota; Czarnowska, Elżbieta; Sowińska, Agnieszka

    2018-01-01

    Chemotherapy, neoplasms, and their complications linked to malabsorption, malnutrition, and metabolic disorders may lead to improper tooth development and frequent severe caries in patients during/after antineoplastic treatment and to a more frequent improper tooth development in patients undergoing chemotherapy during odontogenesis. However, the causes of these abnormalities remain unknown; there are no studies on the impact of antineoplastic treatment and its complications on the chemical composition of mineralised teeth. To compare the chemical composition of mineralised teeth extracted due to complicated caries in children after chemotherapy, and of teeth extracted due to orthodontic treatment in generally healthy children. The treatment group included five teeth extracted due to complicated caries in children after antineoplastic treatment. The control group included five teeth extracted due to orthodontic treatment in generally healthy children. The chemical composition of enamel, dentine, cementum, interior of the canal, and enamel abnormalities in teeth extracted from patients after chemotherapy and in generally healthy patients were assessed with energy-dispersive X-ray spectroscopy. Results were analysed statistically. The magnesium (Mg) and zinc (Zn) mass contents in the enamel of patients after chemotherapy increased and so did the calcium (Ca) to phosphorus (P) ratio when compared to controls. Areas with abnormal enamel in patients after chemotherapy had lower concentrations of Ca and P, and higher concentrations of trace elements (Mg, Cl, and Na). The levels of the assessed elements in dentine, cementum, and inside the canal were similar in both groups of teeth.

  13. The encapsulation of an amphiphile into polystyrene microspheres of narrow size distribution

    Directory of Open Access Journals (Sweden)

    Pellach Michal

    2011-12-01

    Full Text Available Abstract Encapsulation of compounds into nano- or microsized organic particles of narrow size distribution is of increasing importance in fields of advanced imaging and diagnostic techniques and drug delivery systems. The main technology currently used for encapsulation of molecules within uniform template particles while retaining their size distribution is based on particle swelling methodology, involving penetration of emulsion droplets into the particles. The swelling method, however, is efficient for encapsulation only of hydrophobic compounds within hydrophobic template particles. In order to be encapsulated, the molecules must favor the hydrophobic phase of an organic/aqueous biphasic system, which is not easily achieved for molecules of amphiphilic character. The following work overcomes this difficulty by presenting a new method for encapsulation of amphiphilic molecules within uniform hydrophobic particles. We use hydrogen bonding of acid and base, combined with a pseudo salting out effect, for the entrapment of the amphiphile in the organic phase of a biphasic system. Following the entrapment in the organic phase, we demonstrated, using fluorescein and (antibiotic tetracycline as model molecules, that the swelling method usually used only for hydrophobes can be expanded and applied to amphiphilic molecules.

  14. Cardiotoxicity of copper-based antineoplastic drugs casiopeinas is related to inhibition of energy metabolism

    International Nuclear Information System (INIS)

    Hernandez-Esquivel, Luz; Marin-Hernandez, Alvaro; Pavon, Natalia; Carvajal, Karla; Moreno-Sanchez, Rafael

    2006-01-01

    Isolated rat hearts were perfused with glucose, octanoate or glucose + octanoate and different concentrations of the copper-based antineoplastic drugs casiopeina II-gly (CSII) or casiopeina III-i-a (CSIII). In isolated perfused hearts with glucose + octanoate, both casiopeinas induced diminution in cardiac work and O 2 consumption with half-maximal inhibitory concentrations (IC 5 ) of 4 (CSII) and 4.6 (CSIII) μM, after 1 h of perfusion. Strong inhibition of the pyruvate and 2-oxoglutarate dehydrogenases as well as total creatine kinase by casiopeinas suggested that ATP generation by oxidative phosphorylation and its transfer towards myofibrils were targets for these drugs. In consequence, the cellular contents of ATP and phosphocreatine were also lowered by casiopeinas. Remarkably, casiopeinas were less toxic than adriamycin (IC 5 = 2.6 μM), a well-known potent cardiotoxic and antineoplastic drug, which has a wide clinical use. In an open-chest animal, which is a more physiological model than the isolated heart, femoral administration of 1 μM drug revealed that CSII was innocuous very likely due to strong binding to serum albumin, whereas adriamycin induced again a potent cardiotoxic effect (diminution in heart rate and severe depression of systolic blood pressure). Thus, it seems that casiopeinas are a group of new antineoplastic drugs with milder secondary toxic effects than proven drugs such as adriamycin

  15. Novel functional materials from renewable lipids: Amphiphilic antimicrobial polymers and latent heat thermal energy storage

    Science.gov (United States)

    Floros, Michael Christopher

    Vegetable oils represent an ideal and renewable feedstock for the synthesis of a variety of functional materials. However, without financial incentive or unique applications motivating a switch, commercial products continue to be manufactured from petrochemical resources. Two different families of high value, functional materials synthesized from vegetable oils were studied. These materials demonstrate superior and unique performance to comparable petrochemical analogues currently on the market. In the first approach, 3 amphiphilic thermoplastic polytriazoles with differing lipophilic segment lengths were synthesized in a polymerization process without solvents or catalysts. Investigation of monomer structure influence on the resultant functional behaviour of these polymers found distinctive odd/even behaviour reliant on the number of carbon atoms in the monomers. Higher concentrations of triazole groups, due to shorter CH2 chains in the monomeric dialkynes, resulted in more brittle polymers, displaying higher tensile strengths but reduced elongation to break characteristics. These polymers had similar properties to commercial petroleum derived thermoplastics. One polymer demonstrated self-assembled surface microstructuring, and displayed hydrophobic properties. Antimicrobial efficacy of the polymers were tested by applying concentrated bacterial solutions to the surfaces, and near complete inhibition was demonstrated after 4 hours. Scanning electron microscope images of killed bacteria showed extensive membrane damage, consistent with the observed impact of other amphiphilic compounds in literature. These polytriazoles are suited for applications in medical devices and implants, where major concerns over antibiotic resistance are prevalent. In the second approach, a series of symmetric, saturated diester phase change materials (PCMs) were also synthesized with superior latent heat values compared to commercial petrochemical analogues. These diesters exhibit

  16. Molecular discriminators using single wall carbon nanotubes

    International Nuclear Information System (INIS)

    Bhattacharyya, Tamoghna; Dasgupta, Anjan Kr; Ray, Nihar Ranjan; Sarkar, Sabyasachi

    2012-01-01

    The interaction between single wall carbon nanotubes (SWNTs) and amphiphilic molecules has been studied in a solid phase. SWNTs are allowed to interact with different amphiphilic probes (e.g. lipids) in a narrow capillary interface. Contact between strong hydrophobic and amphiphilic interfaces leads to a molecular restructuring of the lipids at the interface. The geometry of the diffusion front and the rate and the extent of diffusion of the interface are dependent on the structure of the lipid at the interface. Lecithin having a linear tail showed greater mobility of the interface as compared to a branched tail lipid like dipalmitoyl phosphatidylcholine, indicating the hydrophobic interaction between single wall carbon nanotube core and the hydrophobic tail of the lipid. Solid phase interactions between SWNT and lipids can thus become a very simple but efficient means of discriminating amphiphilic molecules in general and lipids in particular. (paper)

  17. Electrostatically Driven Assembly of Charged Amphiphiles Forming Crystallized Membranes, Vesicles and Nanofiber Arrays

    Science.gov (United States)

    Leung, Cheuk Yui Curtis

    Charged amphiphilic molecules can self-assemble into a large variety of objects including membranes, vesicles and fibers. These micro to nano-scale structures have been drawing increasing attention due to their broad applications, especially in biotechnology and biomedicine. In this dissertation, three self-assembled systems were investigated: +3/-1 self-assembled catanionic membranes, +2/-1 self-assembled catanionic membranes and +1 self-assembled nanofibers. Transmission electron microscopy (TEM) combined with synchrotron small and wide angle x-ray scattering (SAXS and WAXS) were used to characterize the coassembled structures from the mesoscopic to nanometer scale. We designed a system of +3 and -1 ionic amphiphiles that coassemble into crystalline ionic bilayer vesicles with large variety of geometries that resemble polyhedral cellular crystalline shells and archaea wall envelopes. The degree of ionization of the amphiphiles and their intermolecular electrostatic interactions can be controlled by varying pH. The molecular packing of these membranes showed a hexagonal to rectangular-C to hexagonal phase transition with increasing pH, resulting in significant changes to the membrane morphology. A similar mixture of +2 and -1 ionic amphiphiles was also investigated. In addition to varying pH, which controls the headgroup attractions, we also adjust the tail length of the amphiphiles to control the van der Waals interactions between the tails. A 2D phase diagram was developed to show how pH and tail length can be used to control the intermolecular packing within the membranes. Another system of self-assembled nanofiber network formed by positively charged amphiphiles was also studied. These highly charged fibers repel each other and are packed in hexagonal lattice with lattice constant at least eight times of the fiber diameter. The d-spacing and the crystal structure can be controlled by varying the solution concentration and temperature.

  18. Lack of genotoxicity in medical oncology nurses handling antineoplastic drugs: effect of work environment and protective equipment.

    Science.gov (United States)

    Gulten, Tuna; Evke, Elif; Ercan, Ilker; Evrensel, Turkkan; Kurt, Ender; Manavoglu, Osman

    2011-01-01

    In this study we aimed to investigate the genotoxic effects of antineoplastic agents in occupationally exposed oncology nurses. Genotoxic effects mean the disruptive effects in the integrity of DNA and they are associated with cancer development. Biomonitoring of health care workers handling antineoplastic agents is helpful for the evaluation of exposure to cytostatics. The study included an exposed and two control groups. The exposed group (n=9) was comprised of oncology nurses. The first (n=9) and second (n=10) control groups were comprised of subjects who did not come into contact with antineoplastic drugs working respectively in the same department with oncology nurses and in different departments. Genotoxicity evaluation was performed using SCE analysis. After applying culture, harvest and chromosome staining procedures, a total of 25 metaphases were analyzed per person. Kruskal Wallis test was used to perform statistical analysis. A statistically significant difference of sister chromatid exchange frequencies was not observed between the exposed and control groups. Lack of genotoxicity in medical oncology nurses might be due to good working conditions with high standards of technical equipment and improved personal protection.

  19. Fabrication of Propeller-Shaped Supra-amphiphile for Construction of Enzyme-Responsive Fluorescent Vesicles.

    Science.gov (United States)

    Li, Jie; Liu, Kaerdun; Han, Yuchun; Tang, Ben Zhong; Huang, Jianbin; Yan, Yun

    2016-10-04

    Propeller-shaped molecules have been recognized to display fantastic AIE (aggregation induced emission), but they can hardly self-assemble into nanostructures. Herein, we for the first time report that ionic complexation between a water-soluble tetrapheneyl derivative and an enzyme substrate in aqueous media produces a propeller-shaped supra-amphiphile that self-assembles into enzyme responsive fluorescent vesicles. The supra-amphiphile was fabricated upon complexation between a water-soluble propeller-shaped AIE luminogen TPE-BPA and myristoylcholine chloride (MChCl) in aqueous media. MChCl filled in the intramolecular voids of propeller-shaped TPE-BPA upon supra-amphiphile formation, which endows the supra-amphiphile superior self-assembling ability to the component molecules thus leading to the formation of fluorescent vesicles. Because MChCl is the substrate of cholinesterases, the vesicles dissemble in the presence of cholinesterases, and the fluorescent intensity can be correlated to the level of enzymes. The resulting fluorescent vesicles may be used to recognize the site of Alzheimer's disease, to encapsulate the enzyme inhibitor, and to release the inhibitor at the disease site.

  20. Amphiphilic block co-polymers: preparation and application in nanodrug and gene delivery.

    Science.gov (United States)

    Xiong, Xiao-Bing; Binkhathlan, Ziyad; Molavi, Ommoleila; Lavasanifar, Afsaneh

    2012-07-01

    Self-assembly of amphiphilic block co-polymers composed of poly(ethylene oxide) (PEO) as the hydrophilic block and poly(ether)s, poly(amino acid)s, poly(ester)s and polypropyleneoxide (PPO) as the hydrophobic block can lead to the formation of nanoscopic structures of different morphologies. These structures have been the subject of extensive research in the past decade as artificial mimics of lipoproteins and viral vectors for drug and gene delivery. The aim of this review is to provide an overview of the synthesis of commonly used amphiphilic block co-polymers. It will also briefly go over some pharmaceutical applications of amphiphilic block co-polymers as "nanodelivery systems" for small molecules and gene therapeutics. Copyright © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  1. Amphiphilic brushes from metallo-supramolecular block copolymers

    NARCIS (Netherlands)

    Guillet, P.; Fustin, C.A.; Wouters, D.; Höppener, S.; Schubert, U.S.; Gohy, J.M.W.

    2009-01-01

    A novel strategy to control the formation of amphiphilic brushes from metallo-supramol. block copolymers is described. The investigated copolymer consists of a polystyrene block linked to a poly(ethylene oxide) one via a charged bis-terpyridine ruthenium(ii) complex (PS-[Ru]-PEO). The initial

  2. Diagram of state of stiff amphiphilic macromolecules

    NARCIS (Netherlands)

    Markov, Vladimir A.; Vasilevskaya, Valentina V.; Khalatur, Pavel G.; ten Brinke, Gerrit; Khokhlov, Alexei R.

    2007-01-01

    We studied coil-globule transitions in stiff-chain amphiphilic macromolecules via computer modeling and constructed phase diagrams for such molecules in terms of solvent quality and persistence length. We showed that the shape of the phase diagram essentially depends on the macromolecule degree of

  3. Infiltrative Lung Diseases: Complications of Novel Antineoplastic Agents in Patients with Hematological Malignancies

    Directory of Open Access Journals (Sweden)

    Bobbak Vahid

    2008-01-01

    Full Text Available Infiltrative lung disease is a well-known complication of antineoplastic agents in patients with hematological malignancies. Novel agents are constantly being added to available treatments. The present review discusses different pulmonary syndromes, pathogenesis and management of these novel agents.

  4. Cost-benefit analysis of prophylactic granulocyte colony-stimulating factor during CHOP antineoplastic therapy for non-Hodgkin's lymphoma.

    Science.gov (United States)

    Dranitsaris, G; Altmayer, C; Quirt, I

    1997-06-01

    Several randomised comparative trials have shown that granulocyte colony-stimulating factor (G-CSF) reduces the duration of neutropenia, hospitalisation and intravenous antibacterial use in patients with cancer who are receiving high-dosage antineoplastic therapy. However, one area that has received less attention is the role of G-CSF in standard-dosage antineoplastic regimens. One such treatment that is considered to have a low potential for inducing fever and neutropenia is the CHOP regimen (cyclophosphamide, doxorubicin, vincristine and prednisone) for non-Hodgkin's lymphoma. We conducted a cost-benefit analysis from a societal perspective in order to estimate the net cost or benefit of prophylactic G-CSF in this patient population. This included direct costs for hospitalisation with antibacterial support, as well as indirect societal costs, such as time off work and antineoplastic therapy delays secondary to neutropenia. The findings were then tested by a comprehensive sensitivity analysis. The administration of G-CSF at a dosage of 5 micrograms/kg/day for 11 doses following CHOP resulted in an overall net cost of $Can1257. In the sensitivity analysis, lowering the G-CSF dosage to 2 micrograms/kg/day generated a net benefit of $Can6564, indicating a situation that was cost saving to society. The results of the current study suggest that the use of G-CSF in patients receiving CHOP antineoplastic therapy produces a situation that is close to achieving cost neutrality. However, low-dosage (2 micrograms/kg/day) G-CSF is an economically attractive treatment strategy because it may result in overall savings to society.

  5. Sugar-based amphiphilic polymers for biomedical applications: from nanocarriers to therapeutics.

    Science.gov (United States)

    Gu, Li; Faig, Allison; Abdelhamid, Dalia; Uhrich, Kathryn

    2014-10-21

    Various therapeutics exhibit unfavorable physicochemical properties or stability issues that reduce their in vivo efficacy. Therefore, carriers able to overcome such challenges and deliver therapeutics to specific in vivo target sites are critically needed. For instance, anticancer drugs are hydrophobic and require carriers to solubilize them in aqueous environments, and gene-based therapies (e.g., siRNA or pDNA) require carriers to protect the anionic genes from enzymatic degradation during systemic circulation. Polymeric micelles, which are self-assemblies of amphiphilic polymers (APs), constitute one delivery vehicle class that has been investigated for many biomedical applications. Having a hydrophobic core and a hydrophilic shell, polymeric micelles have been used as drug carriers. While traditional APs are typically comprised of nondegradable block copolymers, sugar-based amphiphilic polymers (SBAPs) synthesized by us are comprised of branched, sugar-based hydrophobic segments and a hydrophilic poly(ethylene glycol) chain. Similar to many amphiphilic polymers, SBAPs self-assemble into polymeric micelles. These nanoscale micelles have extremely low critical micelle concentrations offering stability against dilution, which occurs with systemic administration. In this Account, we illustrate applications of SBAPs for anticancer drug delivery via physical encapsulation within SBAP micelles and chemical conjugation to form SBAP prodrugs capable of micellization. Additionally, we show that SBAPs are excellent at stabilizing liposomal delivery systems. These SBAP-lipid complexes were developed to deliver hydrophobic anticancer therapeutics, achieving preferential uptake in cancer cells over normal cells. Furthermore, these complexes can be designed to electrostatically complex with gene therapies capable of transfection. Aside from serving as a nanocarrier, SBAPs have also demonstrated unique bioactivity in managing atherosclerosis, a major cause of cardiovascular

  6. Improved insulin loading in poly (lactic-co-glycolic) acid (PLGA) nanoparticles upon self-assembly with lipids

    DEFF Research Database (Denmark)

    Garcia Diaz, Maria; Foged, Camilla; Nielsen, Hanne Mørck

    2015-01-01

    Polymeric nanoparticles are widely investigated as drug delivery systems for oral administration. However, the hydrophobic nature of many polymers hampers effective loading of the particles with hydrophilic macromolecules such as insulin. Thus, the aim of this work was to improve the loading...... of insulin into poly(lactic-co-glycolic) acid (PLGA) nanoparticles by pre-assembly with amphiphilic lipids. Insulin was complexed with soybean phosphatidylcholine or sodium caprate by self-assembly and subsequently loaded into PLGA nanoparticles by using the double emulsion-solvent evaporation technique...... efficiencies (90% as compared to 24% in the absence of lipids). Importantly, the insulin loading capacity was increased up to 20% by using the lipid–insulin complexes. The results further showed that a main fraction of the lipid was incorporated into the nanoparticles and remained associated to the polymer...

  7. Facially amphiphilic thiol capped gold and silver nanoparticles

    Indian Academy of Sciences (India)

    Abstract. A series of bile acid-derived facially amphiphilic thiols have been used to cap sliver and gold nanoparticles. The self-assembling properties of these steroid-capped nanoparticles have been investigated and reported in this article.

  8. Isentropic expansion and related thermodynamic properties of non-ionic amphiphile-water mixtures.

    Science.gov (United States)

    Reis, João Carlos R; Douhéret, Gérard; Davis, Michael I; Fjellanger, Inger Johanne; Høiland, Harald

    2008-01-28

    A concise thermodynamic formalism is developed for the molar isentropic thermal expansion, ES,m = ( partial differential Vm/ partial differential T)(Sm,x), and the ideal and excess quantities for the molar, apparent molar and partial molar isentropic expansions of binary liquid mixtures. Ultrasound speeds were determined by means of the pulse-echo-overlap method in aqueous mixtures of 2-methylpropan-2-ol at 298.15 K over the entire composition range. These data complement selected extensive literature data on density, isobaric heat capacity and ultrasound speed for 9 amphiphile (methanol, ethanol, propan-1-ol, propan-2-ol, 2-methylpropan-2-ol, ethane-1,2-diol, 2-methoxyethanol, 2-ethoxyethanol or 2-butoxyethanol)-water binary systems, which form the basis of tables listing molar and excess molar isobaric expansions and heat capacities, and molar and excess molar isentropic compressions and expansions at 298.15 K and at 65 fixed mole fractions spanning the entire composition range and fine-grained in the water-rich region. The dependence on composition of these 9 systems is graphically depicted for the excess molar isobaric and isentropic expansions and for the excess partial molar isobaric and isentropic expansions of the amphiphile. The analysis shows that isentropic thermal expansion properties give a much stronger response to amphiphile-water molecular interactions than do their isobaric counterparts. Depending on the pair property-system, the maximum excess molar isentropic value is generally twenty- to a hundred-fold greater than the corresponding maximum isobaric value, and occurs at a lower mole fraction of the amphiphile. Values at infinite dilution of the 9 amphiphiles in water are given for the excess partial molar isobaric heat capacity, isentropic compression, isobaric expansion and isentropic expansion. These values are interpreted in terms of the changes occurring when amphiphile molecules cluster into an oligomeric form. Present results are discussed

  9. A study protocol for the evaluation of occupational mutagenic/carcinogenic risks in subjects exposed to antineoplastic drugs: a multicentric project

    Directory of Open Access Journals (Sweden)

    Gelatti Umberto

    2011-03-01

    Full Text Available Abstract Background Some industrial hygiene studies have assessed occupational exposure to antineoplastic drugs; other epidemiological investigations have detected various toxicological effects in exposure groups labeled with the job title. In no research has the same population been studied both environmentally and epidemiologically. The protocol of the epidemiological study presented here uses an integrated environmental and biological monitoring approach. The aim is to assess in hospital nurses preparing and/or administering therapy to cancer patients the current level of occupational exposure to antineoplastic drugs, DNA and chromosome damage as cancer predictive effects, and the association between the two. Methods/Design About 80 healthy non-smoking female nurses, who job it is to prepare or handle antineoplastic drugs, and a reference group of about 80 healthy non-smoking female nurses not occupationally exposed to chemicals will be examined simultaneously in a cross-sectional study. All the workers will be recruited from five hospitals in northern and central Italy after their informed consent has been obtained. Evaluation of surface contamination and dermal exposure to antineoplastic drugs will be assessed by determining cyclophosphamide on selected surfaces (wipes and on the exposed nurses' clothes (pads. The concentration of unmetabolized cyclophosphamide as a biomarker of internal dose will be measured in end-shift urine samples from exposed nurses. Biomarkers of effect and susceptibility will be assessed in exposed and unexposed nurses: urinary concentration of 8-hydroxy-2-deoxyguanosine; DNA damage detected using the single-cell microgel electrophoresis (comet assay in peripheral white blood cells; micronuclei and chromosome aberrations in peripheral blood lymphocytes. Genetic polymorphisms for enzymes involved in metabolic detoxification (i.e. glutathione S-transferases will also be analysed. Using standardized questionnaires

  10. Morphological changes of monolayers of two polymerizable pyridine amphiphiles upon complexation with Cu(II) ions at the air-water interface

    NARCIS (Netherlands)

    Werkman, P.J.; Schouten, A.J.; Noordegraaf, M.A.; Kimkes, P.; Sudhölter, E.J.R.

    1998-01-01

    The monolayer behavior of two amphiphilic, diacetylenic units containing pyridine Ligands at the air-water interface is studied by measuring the surface pressure-area isotherms and by Brewster angle microscopy(BAM). Both amphiphiles form stable monolayers at the air-water interface. The amphiphile

  11. Effect of ionizing radiation exposure in the morphology of modified HDPE with amphiphilic particles

    International Nuclear Information System (INIS)

    Saldanha, Ana Luiza M.; Vivas, Viviane; Zylberberg, Marcel P.; Silva, Tamara I.; Cardoso, Andre Luis V.; Pereira, Iaci M.; Patricio, Patricia S.O.

    2015-01-01

    One of the techniques used to improve the properties of high performance polymers is the addition of hybrid particles in the polymer. In this context, amphiphilic particles were synthesized in order to provide surface characteristics that enhance the interaction of the interface with the polymeric matrix of high density polyethylene (HDPE). The amphiphilic particles were added to matrix of HDPE and the modified polymer composites were exposed to ionizing radiation (x-rays) for different times. The changes caused by exposure to ionizing radiation in the composite morphology was observed through the small angle x-ray technique. The results suggest that the addition of amphiphilic particles increased the stability of the composite to degradation by radiation. (author)

  12. Self-Assembly of Amphiphilic Block Copolypeptoids with C 2 -C 5 Side Chains in Aqueous Solution

    KAUST Repository

    Fetsch, Corinna; Flecks, Silvana; Gieseler, Dan; Marschelke, Claudia; Ulbricht, Juliane; van Pé e, Karl-Heinz; Luxenhofer, Robert

    2014-01-01

    © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Nowadays, amphiphilic molecules play an important role in our life. In medical applications, amphiphilic block copolymers have attracted much attention as excipients in drug delivery systems. Here

  13. Micro- and nanophase separations in hierarchical self-assembly of strongly amphiphilic block copolymer-based ionic supramolecules

    DEFF Research Database (Denmark)

    Ayoubi, Mehran Asad; Zhu, Kaizheng; Nyström, Bo

    2013-01-01

    block), a class of ionic supramolecules are successfully synthesized whose molecular architecture consists of a poly(styrene) PS block (Linear block) covalently connected to a strongly amphiphilic comb-like block (AmphComb block), i.e. Linear-b-AmphComb. In the melt state, these ionic supramolecules can.......20 (SLL/C and SBCC/C) and ∼0.28 (C/L). Finally, the specific influences of the strongly amphiphilic nature of the AmphComb blocks on the observed morphological and hierarchical behaviours of our system are discussed. For reference, stoichiometric strongly amphiphilic comb-like (AmphComb) ionic...

  14. Facially amphiphilic thiol capped gold and silver nanoparticles

    Indian Academy of Sciences (India)

    Wintec

    *For correspondence. Also at the Chemical Biology Unit,. Jawaharlal Nehru Centre for Advanced Scientific Research,. Bangalore 560 064. Facially amphiphilic thiol capped gold and silver nanoparticles. †. SHREEDHAR BHAT a and UDAY MAITRA*. Department of Organic Chemistry, Indian Institute of Science, Bangalore ...

  15. Nucleic acid amphiphiles : synthesis and self-assembled nanostructures

    NARCIS (Netherlands)

    Kwak, Minseok; Herrmann, Andreas; Clever, Guido; Mao, Chengde; Shionoya, Mitsuhiko; Stulz, Eugen

    2011-01-01

    This review provides an overview of a relatively new class of bio-conjugates, DNA amphiphiles, which consist of oligonucleotides covalently bonded to synthetic hydrophobic units. The reader will find the basic principles for the structural design and preparation methods of the materials. Moreover,

  16. Ammonium amphiphiles carrying mesogenic units : synthesis, properties, applications

    NARCIS (Netherlands)

    Everaars, M.D.

    1997-01-01

    When the structural characteristics of amphiphiles and thermotropic liquid crystals are combined in one molecule i.e. a polar headgroup with apolar tails and mesogenic units, compounds are obtained which can exhibit both thermotropic and lyotropic mesomorphism. This class of compounds is

  17. [Implementation of a robot for the preparation of antineoplastic drugs in the Pharmacy Service].

    Science.gov (United States)

    Pacheco Ramos, María de la Paz; Arenaza Peña, Ainhoa Elisa; Santiago Pérez, Alejandro; Bilbao Gómez-Martino, Cristina; Zamora Barrios, María Dolores; Arias Fernández, María Lourdes

    2015-05-01

    To describe the implementation of a robot for the preparation of antineoplastic drugs in the Pharmacy Service and to be able to analyze the added value to pharmacotherapy. The implementation was carried out in June 2012 at a tertiary level Hospital, taking place in two periods: 1- test period with the installation of the robot, with technical configuration of the equipment and validation of 29 active ingredients and the integration of electronic prescribing software with the robot application (9 months). 2- Usage period (22 months). On the other hand, training was given to pharmacists and nurses. The robot uses image recognition, barcode identification and gravimetric controls for proper operation. These checks provide information about the error ratio in the preparation, with a margin of ± 10%, which after a pilot study was restricted to a range of ±4%. The robot was programmed to recognize bags, infusion pumps, syringes and vials. The added value was assessed for 31 months by identifying preparation's errors. 11,865 preparations were made by the robot, which meant approximately 40% of all antineoplastic prepared from 29 different active ingredients. 1.12% (n=133) of the errors were identified by the robot and therefore didn't reach the patient (negative desviation - 4%). These errors were corrected manually. The implementation of a robot in the preparation of antineoplastic drugs allows to identify errors therefore preventing them to arrive to the patient. This promotes safety and quality of the process, reducing the exposure to cytotoxic drugs from the manipulator. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  18. Implementation of a robot for the preparation of antineoplastic drugs in the Pharmacy Service

    Directory of Open Access Journals (Sweden)

    María de la Paz Pacheco Ramos

    2015-01-01

    Full Text Available Objective: To describe the implementation of a robot for the preparation of antineoplastic drugs in the Pharmacy Service and to be able to analyze the added value to pharmacotherapy. Methods: The implementation was carried out in June 2012 at a tertiary level Hospital, taking place in two periods: 1- test period with the installation of the robot, with technical configuration of the equipment and validation of 29 active ingredients and the integration of electronic prescribing software with the robot application (9 months. 2- Usage period (22 months. On the other hand, training was given to pharmacists and nurses. The robot uses image recognition, barcode identification and gravimetric controls for proper operation. These checks provide information about the error ratio in the preparation, with a margin of ± 10%, which after a pilot study was restricted to a range of ±4%. The robot was programmed to recognize bags, infusion pumps, syringes and vials. The added value was assessed for 31 months by identifying preparation´s errors. Results: 11,865 preparations were made by the robot, which meant approximately 40% of all antineoplastic prepared from 29 different active ingredients. 1.12% (n=133 of the errors were identified by the robot and therefore didn´t reach the patient (negative desviation - 4%. These errors were corrected manually. Conclusion: The implementation of a robot in the preparation of antineoplastic drugs allows to identify errors therefore preventing them to arrive to the patient. This promotes safety and quality of the process, reducing the exposure to cytotoxic drugs from the manipulator

  19. The search for new amphiphiles: synthesis of a modular, high-throughput library

    Directory of Open Access Journals (Sweden)

    George C. Feast

    2014-07-01

    Full Text Available Amphiphilic compounds are used in a variety of applications due to their lyotropic liquid-crystalline phase formation, however only a limited number of compounds, in a potentially limitless field, are currently in use. A library of organic amphiphilic compounds was synthesised consisting of glucose, galactose, lactose, xylose and mannose head groups and double and triple-chain hydrophobic tails. A modular, high-throughput approach was developed, whereby head and tail components were conjugated using the copper-catalysed azide–alkyne cycloaddition (CuAAC reaction. The tails were synthesised from two core alkyne-tethered intermediates, which were subsequently functionalised with hydrocarbon chains varying in length and degree of unsaturation and branching, while the five sugar head groups were selected with ranging substitution patterns and anomeric linkages. A library of 80 amphiphiles was subsequently produced, using a 24-vial array, with the majority formed in very good to excellent yields. A preliminary assessment of the liquid-crystalline phase behaviour is also presented.

  20. Liquid-solid extraction of metallic cations by cationic amphiphiles

    International Nuclear Information System (INIS)

    Mueller, Wolfram; Sievers, Torsten K.; Zemb, Thomas; Diat, Olivier; Sievers, Torsten K.; Dejugnat, Christophe

    2012-01-01

    In the field of selective metal ion separation, liquid-liquid extraction is usually conducted through an emulsion mixing of hydrophobic complexants dispersed in an organic phase and acidic water containing the ionic species. Recently, it has been shown that amphiphilic complexants could influence strongly extraction efficiency by enhancing the interfacial interaction between the metal ion in the aqueous and the complexant in the organic phase. Moreover, these amphiphiles can also substitute the organic phase if an appropriate aliphatic chain is chosen. The dispersion of such amphiphilic complexants in an aqueous solution of salt mixtures is not only attractive for studying specific interactions but also to better the understanding of complex formation in aqueous solution of multivalent metal ions, such as lanthanides and actinides. This understanding is of potential interest for a broad range of industries including purification of rare earth metals and pollute treatment e.g. of fission byproducts. This principle can also be applied to liquid-solid extraction, where the final state of the separation is a solid phase containing the selectively extracted ions. Indeed, a novel solid-liquid extraction method exploits the selective precipitation of metal ions from an aqueous salt mixture using a cationic surfactant, below its Krafft point (temperature below which the long aliphatic chains of surfactant crystallize). This technique has been proven to be highly efficient for the separation of actinides and heavy metal using long chain ammonium or pyridinium amphiphiles. The most important point in this process is the recognition of cationic metal ions by cationic surfactants. By computing the free energy of the polar head group per micelle as a function of the different counter-anions, we have demonstrated for the first time that different interactions exist between the micellar surface and the ions. These interactions depend on the nature of the cation but also on

  1. Biomimetic surface coatings from modular amphiphilic proteins

    Science.gov (United States)

    Harden, James; Wan, Fan; Fischer, Stephen; Dick, Scott

    2010-03-01

    Recombinant DNA methods have been used to develop a library of diblock protein polymers for creating designer biofunctional interfaces. These proteins are composed of a surface-active, amphiphilic block joined to a disordered, water soluble block with an end terminal bioactive domain. The amphiphilic block has a strong affinity for many synthetic polymer surfaces, providing a facile means of imparting biological functionality to otherwise bio-neutral materials through physical self-assembly. We have incorporated a series of bioactive end domains into this diblock motif, including sequences that encode specific cell binding and signaling functions of extracellular matrix constituents (e.g. RGD and YIGSR). In this talk, we show that these diblock constructs self-assemble into biofunctional surface coatings on several model synthetic polymer materials. We demonstrate that surface adsorption of the proteins has minimal impacts on the presentation of the bioactive domains in the soluble block, and through the use of microscopic and cell proliferation assays, we show that the resulting biofunctional interfaces are capable of inducing appropriate cellular responses in a variety of human cell types.

  2. Maltose-neopentyl glycol (MNG) amphiphiles for solubilization, stabilization and crystallization of membrane proteins.

    Science.gov (United States)

    Chae, Pil Seok; Rasmussen, Søren G F; Rana, Rohini R; Gotfryd, Kamil; Chandra, Richa; Goren, Michael A; Kruse, Andrew C; Nurva, Shailika; Loland, Claus J; Pierre, Yves; Drew, David; Popot, Jean-Luc; Picot, Daniel; Fox, Brian G; Guan, Lan; Gether, Ulrik; Byrne, Bernadette; Kobilka, Brian; Gellman, Samuel H

    2010-12-01

    The understanding of integral membrane protein (IMP) structure and function is hampered by the difficulty of handling these proteins. Aqueous solubilization, necessary for many types of biophysical analysis, generally requires a detergent to shield the large lipophilic surfaces of native IMPs. Many proteins remain difficult to study owing to a lack of suitable detergents. We introduce a class of amphiphiles, each built around a central quaternary carbon atom derived from neopentyl glycol, with hydrophilic groups derived from maltose. Representatives of this maltose-neopentyl glycol (MNG) amphiphile family show favorable behavior relative to conventional detergents, as manifested in multiple membrane protein systems, leading to enhanced structural stability and successful crystallization. MNG amphiphiles are promising tools for membrane protein science because of the ease with which they may be prepared and the facility with which their structures may be varied.

  3. Self-assembly behavior of a linear-star supramolecular amphiphile based on host-guest complexation.

    Science.gov (United States)

    Wang, Juan; Wang, Xing; Yang, Fei; Shen, Hong; You, Yezi; Wu, Decheng

    2014-11-04

    A star polymer, β-cyclodextrin-poly(l-lactide) (β-CD-PLLA), and a linear polymer, azobenzene-poly(ethylene glycol) (Azo-PEG), could self-assemble into a supramolecular amphiphilic copolymer (β-CD-PLLA@Azo-PEG) based on the host-guest interaction between β-CD and azobenzene moieties. This linear-star supramolecular amphiphilic copolymer further self-assembled into a variety of morphologies, including sphere-like micelle, carambola-like micelle, naan-like micelle, shuttle-like lamellae, tube-like fiber, and random curled-up lamellae, by tuning the length of hydrophilic or hydrophobic chains. The variation of morphology was closely related to the topological structure and block ratio of the supramolecular amphiphiles. These self-assembly structures could disassemble upon an ultraviolet (UV) light irradiation.

  4. Interaction pathways between soft lipid nanodiscs and plasma membranes: A molecular modeling study.

    Science.gov (United States)

    Li, Shixin; Luo, Zhen; Xu, Yan; Ren, Hao; Deng, Li; Zhang, Xianren; Huang, Fang; Yue, Tongtao

    2017-10-01

    Lipid nanodisc, a model membrane platform originally synthesized for study of membrane proteins, has recently been used as the carrier to deliver amphiphilic drugs into target tumor cells. However, the central question of how cells interact with such emerging nanomaterials remains unclear and deserves our research for both improving the delivery efficiency and reducing the side effect. In this work, a binary lipid nanodisc is designed as the minimum model to investigate its interactions with plasma membranes by using the dissipative particle dynamics method. Three typical interaction pathways, including the membrane attachment with lipid domain exchange of nanodiscs, the partial membrane wrapping with nanodisc vesiculation, and the receptor-mediated endocytosis, are discovered. For the first pathway, the boundary normal lipids acting as ligands diffuse along the nanodisc rim to gather at the membrane interface, repelling the central bola lipids to reach a stable membrane attachment. If bola lipids are positioned at the periphery and act as ligands, they diffuse to form a large aggregate being wrapped by the membrane, leaving the normal lipids exposed on the membrane exterior by assembling into a vesicle. Finally, by setting both central normal lipids and boundary bola lipids as ligands, the receptor-mediated endocytosis occurs via both deformation and self-rotation of the nanodiscs. All above pathways for soft lipid nanodiscs are quite different from those for rigid nanoparticles, which may provide useful guidelines for design of soft lipid nanodiscs in widespread biomedical applications. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. SYNTHESIS OF AMPHIPHILIC COMB-SHAPED COPOLYMERS USED FOR SURFACE MODIFICATION OF PVDF MEMBRANES

    Institute of Scientific and Technical Information of China (English)

    徐又一

    2009-01-01

    The synthesis of a novel amphiphilic comb-shaped copolymer consisting of a main chain of styrene-(N-(4- hydroxyphenyl) maleimide)(SHMI) copolymer and poly(ethylene glycol) methyl ether methacrylate(PEGMA) side groups was achieved by atom transfer radical polymerization(ATRP).The amphiphilic copolymers were characterized by ~1H-NMR, Fourier transform infrared(FTIR) spectroscopy and gel permeation chromatography(GPC).From thermogravimetric analysis (TGA),the decomposition temperature of SHMI-g-PEGMA is low...

  6. Galactosylated DNA lipid nanocapsules for efficient hepatocyte targeting.

    Science.gov (United States)

    Morille, M; Passirani, C; Letrou-Bonneval, E; Benoit, J-P; Pitard, B

    2009-09-11

    The main objective of gene therapy via a systemic pathway is the development of a stable and non-toxic gene vector that can encapsulate and deliver foreign genetic materials into specific cell types with the transfection efficiency of viral vectors. With this objective, DNA complexed with cationic lipids of DOTAP/DOPE was encapsulated into lipid nanocapsules (LNCs) forming nanocarriers (DNA LNCs) with a size suitable for systemic injection (109+/-6 nm). With the goal of increasing systemic delivery, LNCs were stabilised with long chains of poly(ethylene glycol) (PEG), either from a PEG lipid derivative (DSPE-mPEG(2000)) or from an amphiphilic block copolymer (F108). In order to overcome internalisation difficulties encountered with PEG shield, a specific ligand (galactose) was covalently added at the distal end of the PEG chains, in order to provide active targeting of the asialoglycoprotein-receptor present on hepatocytes. This study showed that DNA LNCs were as efficient as positively charged DOTAP/DOPE lipoplexes for transfection. In primary hepatocytes, when non-galactosylated, the two polymers significantly decreased the transfection, probably by creating a barrier around the DNA LNCs. Interestingly, galactosylated F108 coated DNA LNCs led to a 18-fold increase in luciferase expression compared to non-galactosylated ones.

  7. Adsorption of different amphiphilic molecules onto polystyrene latices.

    Science.gov (United States)

    Jódar-Reyes, A B; Ortega-Vinuesa, J L; Martín-Rodríguez, A

    2005-02-15

    In order to know the influence of the surface characteristics and the chain properties on the adsorption of amphiphilic molecules onto polystyrene latex, a set of experiments to study the adsorption of ionic surfactants, nonionic surfactants and an amphiphilic synthetic peptide on different latex dispersions was performed. The adsorbed amount versus the equilibrium surfactant concentration was determined. The main adsorption mechanism was the hydrophobic attraction between the nonpolar tail of the molecule and the hydrophobic regions of the latex surface. This attraction overcame the electrostatic repulsion between chains and latex surface with identical charge sign. However, the electrostatic interactions chain-surface and chain-chain also played a role. General patterns for the adsorption of ionic chains on charged latex surfaces could be established. Regarding the shape, the isotherms presented different plateaus corresponding to electrostatic effects and conformational changes. The surfactant size also affects the adsorption results: the higher the hydrophilic moiety in the surfactant molecule the lower the adsorbed amount.

  8. Formation and Mechanism of Superhydrophobic/Hydrophobic Surfaces Made from Amphiphiles through Droplet-Mediated Evaporation-Induced Self-Assembly.

    Science.gov (United States)

    Dong, Fangyuan; Zhang, Mi; Tang, Wai-Wa; Wang, Yi

    2015-04-23

    Superhydrophobic/hydrophobic surfaces have attracted wide attention because of their broad applications in various regions, including coating, textile, packaging, electronic devices, and bioengineering. Many studies have been focused on the fabrication of superhydrophobic/hydrophobic surfaces using natural materials. In this paper, superhydrophobic/hydrophobic surfaces were formed by an amphiphilic natural protein, zein, using electrospinning. Water contact angle (WCA) and scanning electron microscopy (SEM) were used to characterize the hydrophobicity and surface morphology of the electrospun structures. The highest WCA of the zein electrospun surfaces could reach 155.5 ± 1.4°. To further understand the mechanism of superhydrophobic surface formation from amphiphiles using electrospinning, a synthetic amphiphilic polymer was selected, and also, a method similar to electrospinning, spray drying, was tried. The electrospun amphiphilic polymer surface showed a high hydrophobicity with a WCA of 141.4 ± 0.7°. WCA of the spray-dried zein surface could reach 125.3 ± 2.1°. The secondary structures of the zein in the electrospun film and cast-dried film were studied using ATR-FTIR, showing that α-helix to β-sheet transformation happened during the solvent evaporation in the cast drying process but not in the electrospinning process. A formation mechanism was proposed on the basis of the orientation of the amphiphiles during the solvent evaporation of different fabrication methods. The droplet-based or jet-based evaporation during electrospinning and spray drying led to the formation of the superhydrophobic/hydrophobic surface by the accumulation of the hydrophobic groups of the amphiphiles on the surface, while the surface-based evaporation during cast drying led to the formation of the hydrophilic surface by the accumulation of the hydrophilic groups of the amphiphiles on the surface.

  9. Lipid-Mediated Clusters of Guest Molecules in Model Membranes and Their Dissolving in the Presence of Lipid Rafts.

    Science.gov (United States)

    Kardash, Maria E; Dzuba, Sergei A

    2017-05-25

    The clustering of molecules is an important feature of plasma membrane organization. It is challenging to develop methods for quantifying membrane heterogeneities because of their transient nature and small size. Here, we obtained evidence that transient membrane heterogeneities can be frozen at cryogenic temperatures which allows the application of solid-state experimental techniques sensitive to the nanoscale distance range. We employed the pulsed version of electron paramagnetic resonance (EPR) spectroscopy, the electron spin echo (ESE) technique, for spin-labeled molecules in multilamellar lipid bilayers. ESE decays were refined for pure contribution of spin-spin magnetic dipole-dipolar interaction between the labels; these interactions manifest themselves at a nanometer distance range. The bilayers were prepared from different types of saturated and unsaturated lipids and cholesterol (Chol); in all cases, a small amount of guest spin-labeled substances 5-doxyl-stearic-acid (5-DSA) or 3β-doxyl-5α-cholestane (DChl) was added. The local concentration found of 5-DSA and DChl molecules was remarkably higher than the mean concentration in the bilayer, evidencing the formation of lipid-mediated clusters of these molecules. To our knowledge, formation of nanoscale clusters of guest amphiphilic molecules in biological membranes is a new phenomenon suggested only recently. Two-dimensional 5-DSA molecular clusters were found, whereas flat DChl molecules were found to be clustered into stacked one-dimensional structures. These clusters disappear when the Chol content is varied between the boundaries known for lipid raft formation at room temperatures. The room temperature EPR evidenced entrapping of DChl molecules in the rafts.

  10. Methotrexate diethyl ester-loaded lipid-core nanocapsules in aqueous solution increased antineoplastic effects in resistant breast cancer cell line.

    Science.gov (United States)

    Yurgel, Virginia C; Oliveira, Catiuscia P; Begnini, Karine R; Schultze, Eduarda; Thurow, Helena S; Leon, Priscila M M; Dellagostin, Odir A; Campos, Vinicius F; Beck, Ruy C R; Guterres, Silvia S; Collares, Tiago; Pohlmann, Adriana R; Seixas, Fabiana K

    2014-01-01

    Breast cancer is the most frequent cancer affecting women. Methotrexate (MTX) is an antimetabolic drug that remains important in the treatment of breast cancer. Its efficacy is compromised by resistance in cancer cells that occurs through a variety of mechanisms. This study evaluated apoptotic cell death and cell cycle arrest induced by an MTX derivative (MTX diethyl ester [MTX(OEt)2]) and MTX(OEt)2-loaded lipid-core nanocapsules in two MTX-resistant breast adenocarcinoma cell lines, MCF-7 and MDA-MB-231. The formulations prepared presented adequate granulometric profile. The treatment responses were evaluated through flow cytometry. Relying on the mechanism of resistance, we observed different responses between cell lines. For MCF-7 cells, MTX(OEt)2 solution and MTX(OEt)2-loaded lipid-core nanocapsules presented significantly higher apoptotic rates than untreated cells and cells incubated with unloaded lipid-core nanocapsules. For MDA-MB-231 cells, MTX(OEt)2-loaded lipid-core nanocapsules were significantly more efficient in inducing apoptosis than the solution of the free drug. S-phase cell cycle arrest was induced only by MTX(OEt)2 solution. The drug nanoencapsulation improved apoptosis induction for the cell line that presents MTX resistance by lack of transport receptors.

  11. Membrane behavior as influenced by partitioning of amphiphiles during drying : a comparative study in anhydrobiotic plant systems

    NARCIS (Netherlands)

    Golovina, E.A.; Hoekstra, F.A.

    2002-01-01

    During cellular desiccation, reduction in volume can in principle cause amphiphilic compounds to partition from the cytoplasm into membranes, with structural perturbance as the result. Here, we studied the effect of partitioning of endogenous amphiphiles on membrane surface dynamics in

  12. Novel amphiphilic poly(dimethylsiloxane) based polyurethane networks tethered with carboxybetaine and their combined antibacterial and anti-adhesive property

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Jingxian; Fu, Yuchen; Zhang, Qinghua, E-mail: qhzhang@zju.edu.cn; Zhan, Xiaoli; Chen, Fengqiu

    2017-08-01

    Highlights: • An amphiphilic poly(dimethylsiloxane) (PDMS) based polyurethane (PU) network tethered with carboxybetaine is prepared. • The surface distribution of PDMS and zwitterionic segments produces an obvious amphiphilic heterogeneous surface. • This designed PDMS-based amphiphilic PU network exhibits combined antibacterial and anti-adhesive properties. - Abstract: The traditional nonfouling materials are powerless against bacterial cells attachment, while the hydrophobic bactericidal surfaces always suffer from nonspecific protein adsorption and dead bacterial cells accumulation. Here, amphiphilic polyurethane (PU) networks modified with poly(dimethylsiloxane) (PDMS) and cationic carboxybetaine diol through simple crosslinking reaction were developed, which had an antibacterial efficiency of 97.7%. Thereafter, the hydrolysis of carboxybetaine ester into zwitterionic groups brought about anti-adhesive properties against bacteria and proteins. The surface chemical composition and wettability performance of the PU network surfaces were investigated by attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS) and contact angle analysis. The surface distribution of PDMS and zwitterionic segments produced an obvious amphiphilic heterogeneous surface, which was demonstrated by atomic force microscopy (AFM). Enzyme-linked immunosorbent assays (ELISA) were used to test the nonspecific protein adsorption behaviors. With the advantages of the transition from excellent bactericidal performance to anti-adhesion and the combination of fouling resistance and fouling release property, the designed PDMS-based amphiphilic PU network shows great application potential in biomedical devices and marine facilities.

  13. Parameters influencing the introduction of plasmid DNA into cells by the use of synthetic amphiphiles as a carrier system

    OpenAIRE

    van der Woude, Irene; Willy Visser, H.; ter Beest, Martin B.A.; Wagenaar, Anno; Ruiters, Marcel H.J.; Engberts, Jan B.F.N.; Hoekstra, Dick

    1995-01-01

    Parameters that affect cellular transfection as accomplished by introducing DNA via carriers composed of cationic synthetic amphiphiles, have been investigated with the aim to obtain insight into the mechanism of DNA translocation. Such insight may be exploited in optimizing carrier properties of synthetic amphiphiles for molecules other than nucleic acids. In the present work, the interaction of vesicles composed of the cationic amphiphile dioleyloxy-propyl-trimethylammonium chloride (DOTMA)...

  14. Loading of Vesicles into Soft Amphiphilic Nanotubes using Osmosis

    NARCIS (Netherlands)

    Erne, Petra M.; van Bezouwen, Laura S.; Stacko, Peter; van Dtjken, Derk Jan; Chen, Jiawen; Stuart, Marc C. A.; Boekema, Eghert J.; Feringa, Ben L.

    2015-01-01

    The facile assembly of higher-order nanoarchitectures from simple building blocks is demonstrated by the loading of vesicles into soft amphiphilic nanotubes using osmosis. The nanotubes are constructed from rigid interdigitated bilayers which are capped with vesicles comprising phospholipid-based

  15. Single histidine residue in head-group region is sufficient to impart remarkable gene transfection properties to cationic lipids: evidence for histidine-mediated membrane fusion at acidic pH.

    Science.gov (United States)

    Kumar, V V; Pichon, C; Refregiers, M; Guerin, B; Midoux, P; Chaudhuri, A

    2003-08-01

    Presence of endosome-disrupting multiple histidine functionalities in the molecular architecture of cationic polymers, such as polylysine, has previously been demonstrated to significantly enhance their in vitro gene delivery efficiencies. Towards harnessing improved transfection property through covalent grafting of endosome-disrupting single histidine functionality in the molecular structure of cationic lipids, herein, we report on the design, the synthesis and the transfection efficiency of two novel nonglycerol-based histidylated cationic amphiphiles. We found that L-histidine-(N,N-di-n-hexadecylamine)ethylamide (lipid 1) and L-histidine-(N,N-di-n-hexadecylamine,-N-methyl)ethylamide (lipid 2) in combination with cholesterol gave efficient transfections into various cell lines. The transfection efficiency of Chol/lipid 1 lipoplexes into HepG2 cells was two order of magnitude higher than that of FuGENE(TM)6 and DC-Chol lipoplexes, whereas it was similar into A549, 293T7 and HeLa cells. A better efficiency was obtained with Chol/lipid 2 lipoplexes when using the cytosolic luciferase expression vector (pT7Luc) under the control of the bacterial T7 promoter. Membrane fusion activity measurements using fluorescence resonance energy transfer (FRET) technique showed that the histidine head-groups of Chol/lipid 1 liposomes mediated membrane fusion in the pH range 5-7. In addition, the transgene expression results using the T7Luc expression vector convincingly support the endosome-disrupting role of the presently described mono-histidylated cationic transfection lipids and the release of DNA into the cytosol. We conclude that covalent grafting of a single histidine amino acid residue to suitable twin-chain hydrophobic compounds is able to impart remarkable transfection properties on the resulting mono-histidylated cationic amphiphile, presumably via the endosome-disrupting characteristics of the histidine functionalities.

  16. Cholesterylbutyrate Solid Lipid Nanoparticles as a Butyric Acid Prodrug

    Directory of Open Access Journals (Sweden)

    Alessandro Mauro

    2008-02-01

    Full Text Available Cholesterylbutyrate (Chol-but was chosen as a prodrug of butyric acid.Butyrate is not often used in vivo because its half-life is very short and therefore too largeamounts of the drug would be necessary for its efficacy. In the last few years butyric acid'santi-inflammatory properties and its inhibitory activity towards histone deacetylases havebeen widely studied, mainly in vitro. Solid Lipid Nanoparticles (SLNs, whose lipid matrixis Chol-but, were prepared to evaluate the delivery system of Chol-but as a prodrug and totest its efficacy in vitro and in vivo. Chol-but SLNs were prepared using the microemulsionmethod; their average diameter is on the order of 100-150 nm and their shape is spherical.The antineoplastic effects of Chol-but SLNs were assessed in vitro on different cancer celllines and in vivo on a rat intracerebral glioma model. The anti-inflammatory activity wasevaluated on adhesion of polymorphonuclear cells to vascular endothelial cells. In thereview we will present data on Chol-but SLNs in vitro and in vivo experiments, discussingthe possible utilisation of nanoparticles for the delivery of prodrugs for neoplastic andchronic inflammatory diseases.

  17. How crystallisation of turkey lysozyme is affected by contamination with hen lysozyme

    DEFF Research Database (Denmark)

    Ishøy, T.; Larsen, S.

    In this project, lipid monolayers at air/water interfaces and lipid-bilayer membranes are used as templates for studying the interaction of peptides and amphiphilic proteins with lipid aggregates. This experimental investigation is related to modelstudies of biological membrane structure and -fun......In this project, lipid monolayers at air/water interfaces and lipid-bilayer membranes are used as templates for studying the interaction of peptides and amphiphilic proteins with lipid aggregates. This experimental investigation is related to modelstudies of biological membrane structure...

  18. Medicinal electronomics bricolage design of hypoxia-targeting antineoplastic drugs and invention of boron tracedrugs as innovative future-architectural drugs.

    Science.gov (United States)

    Hori, Hitoshi; Uto, Yoshihiro; Nakata, Eiji

    2010-09-01

    We describe herein for the first time our medicinal electronomics bricolage design of hypoxia-targeting antineoplastic drugs and boron tracedrugs as newly emerging drug classes. A new area of antineoplastic drugs and treatments has recently focused on neoplastic cells of the tumor environment/microenvironment involving accessory cells. This tumor hypoxic environment is now considered as a major factor that influences not only the response to antineoplastic therapies but also the potential for malignant progression and metastasis. We review our medicinal electronomics bricolage design of hypoxia-targeting drugs, antiangiogenic hypoxic cell radiosensitizers, sugar-hybrid hypoxic cell radiosensitizers, and hypoxia-targeting 10B delivery agents, in which we design drug candidates based on their electronic structures obtained by molecular orbital calculations, not based solely on pharmacophore development. These drugs include an antiangiogenic hypoxic cell radiosensitizer TX-2036, a sugar-hybrid hypoxic cell radiosensitizer TX-2244, new hypoxia-targeting indoleamine 2,3-dioxygenase (IDO) inhibitors, and a hypoxia-targeting BNCT agent, BSH (sodium borocaptate-10B)-hypoxic cytotoxin tirapazamine (TPZ) hybrid drug TX-2100. We then discuss the concept of boron tracedrugs as a new drug class having broad potential in many areas.

  19. Evaluation of real-time data obtained from gravimetric preparation of antineoplastic agents shows medication errors with possible critical therapeutic impact: Results of a large-scale, multicentre, multinational, retrospective study.

    Science.gov (United States)

    Terkola, R; Czejka, M; Bérubé, J

    2017-08-01

    Medication errors are a significant cause of morbidity and mortality especially with antineoplastic drugs, owing to their narrow therapeutic index. Gravimetric workflow software systems have the potential to reduce volumetric errors during intravenous antineoplastic drug preparation which may occur when verification is reliant on visual inspection. Our aim was to detect medication errors with possible critical therapeutic impact as determined by the rate of prevented medication errors in chemotherapy compounding after implementation of gravimetric measurement. A large-scale, retrospective analysis of data was carried out, related to medication errors identified during preparation of antineoplastic drugs in 10 pharmacy services ("centres") in five European countries following the introduction of an intravenous workflow software gravimetric system. Errors were defined as errors in dose volumes outside tolerance levels, identified during weighing stages of preparation of chemotherapy solutions which would not otherwise have been detected by conventional visual inspection. The gravimetric system detected that 7.89% of the 759 060 doses of antineoplastic drugs prepared at participating centres between July 2011 and October 2015 had error levels outside the accepted tolerance range set by individual centres, and prevented these doses from reaching patients. The proportion of antineoplastic preparations with deviations >10% ranged from 0.49% to 5.04% across sites, with a mean of 2.25%. The proportion of preparations with deviations >20% ranged from 0.21% to 1.27% across sites, with a mean of 0.71%. There was considerable variation in error levels for different antineoplastic agents. Introduction of a gravimetric preparation system for antineoplastic agents detected and prevented dosing errors which would not have been recognized with traditional methods and could have resulted in toxicity or suboptimal therapeutic outcomes for patients undergoing anticancer treatment.

  20. [Applying dose banding to the production of antineoplastic drugs: a narrative review of the literature].

    Science.gov (United States)

    Pérez Huertas, Pablo; Cueto Sola, Margarita; Escobar Cava, Paloma; Borrell García, Carmela; Albert Marí, Asunción; López Briz, Eduardo; Poveda Andrés, José Luis

    2015-07-01

    The dosage of antineoplastic drugs has historically been based on individualized prescription and preparation according to body surface area or patient´s weight. Lack of resources and increased assistance workload in the areas where chemotherapy is made, are leading to the development of new systems to optimize the processing without reducing safety. One of the strategies that has been proposed is the elaboration by dose banding. This new approach standardizes the antineoplastic agents doses by making ranges or bands accepting a percentage of maximum variation. It aims to reduce processing time with the consequent reduction in waiting time for patients; to reduce errors in the manufacturing process and to promote the rational drug use. In conclusion, dose banding is a suitable method for optimizing the development of anticancer drugs, obtaining reductions in oncologic patients waiting time but without actually causing a favorable impact on direct or indirect costs. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  1. Applying dose banding to the production of antineoplastic drugs: a narrative review of the literature

    Directory of Open Access Journals (Sweden)

    Pablo Pérez Huertas

    2015-07-01

    Full Text Available The dosage of antineoplastic drugs has historically been based on individualized prescription and preparation according to body surface area or patient´s weight. Lack of resources and increased assistance workload in the areas where chemotherapy is made, are leading to the development of new systems to optimize the processing without reducing safety. One of the strategies that has been proposed is the elaboration by dose banding. This new approach standardizes the antineoplastic agents doses by making ranges or bands accepting a percentage of maximum variation. It aims to reduce processing time with the consequent reduction in waiting time for patients; to reduce errors in the manufacturing process and to promote the rational drug use. In conclusion, dose banding is a suitable method for optimizing the development of anticancer drugs, obtaining reductions in oncologic patients waiting time but without actually causing a favorable impact on direct or indirect costs.

  2. Exploiting lipopolysaccharide-induced deformation of lipid bilayers to modify membrane composition and generate two-dimensional geometric membrane array patterns

    Energy Technology Data Exchange (ETDEWEB)

    Adams, Peter G. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Swingle, Kirstie L. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Univ. of New Mexico, Albuquerque, NM (United States); Paxton, Walter F. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Nogan, John J. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Stromberg, Loreen R. [Univ. of New Mexico, Albuquerque, NM (United States); Firestone, Millicent A. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Mukundan, Harshini [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); New Mexico Consortium, Los Alamos, NM (United States); Montaño, Gabriel A. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-05-27

    Supported lipid bilayers have proven effective as model membranes for investigating biophysical processes and in development of sensor and array technologies. The ability to modify lipid bilayers after their formation and in situ could greatly advance membrane technologies, but is difficult via current state-of-the-art technologies. Here we demonstrate a novel method that allows the controlled post-formation processing and modification of complex supported lipid bilayer arrangements, under aqueous conditions. We exploit the destabilization effect of lipopolysaccharide, an amphiphilic biomolecule, interacting with lipid bilayers to generate voids that can be backfilled to introduce desired membrane components. We further demonstrate that when used in combination with a single, traditional soft lithography process, it is possible to generate hierarchically-organized membrane domains and microscale 2-D array patterns of domains. Significantly, this technique can be used to repeatedly modify membranes allowing iterative control over membrane composition. This approach expands our toolkit for functional membrane design, with potential applications for enhanced materials templating, biosensing and investigating lipid-membrane processes.

  3. Stereocomplex micelle from nonlinear enantiomeric copolymers efficiently transports antineoplastic drug

    Science.gov (United States)

    Wang, Jixue; Shen, Kexin; Xu, Weiguo; Ding, Jianxun; Wang, Xiaoqing; Liu, Tongjun; Wang, Chunxi; Chen, Xuesi

    2015-05-01

    Nanoscale polymeric micelles have attracted more and more attention as a promising nanocarrier for controlled delivery of antineoplastic drugs. Herein, the doxorubicin (DOX)-loaded poly(D-lactide)-based micelle (PDM/DOX), poly(L-lactide)-based micelle (PLM/DOX), and stereocomplex micelle (SCM/DOX) from the equimolar mixture of the enantiomeric four-armed poly(ethylene glycol)-polylactide (PEG-PLA) copolymers were successfully fabricated. In phosphate-buffered saline (PBS) at pH 7.4, SCM/DOX exhibited the smallest hydrodynamic diameter ( D h) of 90 ± 4.2 nm and the slowest DOX release compared with PDM/DOX and PLM/DOX. Moreover, PDM/DOX, PLM/DOX, and SCM/DOX exhibited almost stable D hs of around 115, 105, and 90 nm at above normal physiological condition, respectively, which endowed them with great potential in controlled drug delivery. The intracellular DOX fluorescence intensity after the incubation with the laden micelles was different degrees weaker than that incubated with free DOX · HCl within 12 h, probably due to the slow DOX release from micelles. As the incubation time reached to 24 h, all the cells incubated with the laden micelles, especially SCM/DOX, demonstrated a stronger intracellular DOX fluorescence intensity than free DOX · HCl-cultured ones. More importantly, all the DOX-loaded micelles, especially SCM/DOX, exhibited potent antineoplastic efficacy in vitro, excellent serum albumin-tolerance stability, and satisfactory hemocompatibility. These encouraging data indicated that the loading micelles from nonlinear enantiomeric copolymers, especially SCM/DOX, might be promising in clinical systemic chemotherapy through intravenous injection.

  4. New approaches to wipe sampling methods for antineoplastic and other hazardous drugs in healthcare settings.

    Science.gov (United States)

    Connor, Thomas H; Smith, Jerome P

    2016-09-01

    At the present time, the method of choice to determine surface contamination of the workplace with antineoplastic and other hazardous drugs is surface wipe sampling and subsequent sample analysis with a variety of analytical techniques. The purpose of this article is to review current methodology for determining the level of surface contamination with hazardous drugs in healthcare settings and to discuss recent advances in this area. In addition it will provide some guidance for conducting surface wipe sampling and sample analysis for these drugs in healthcare settings. Published studies on the use of wipe sampling to measure hazardous drugs on surfaces in healthcare settings drugs were reviewed. These studies include the use of well-documented chromatographic techniques for sample analysis in addition to newly evolving technology that provides rapid analysis of specific antineoplastic. Methodology for the analysis of surface wipe samples for hazardous drugs are reviewed, including the purposes, technical factors, sampling strategy, materials required, and limitations. The use of lateral flow immunoassay (LFIA) and fluorescence covalent microbead immunosorbent assay (FCMIA) for surface wipe sample evaluation is also discussed. Current recommendations are that all healthc a re settings where antineoplastic and other hazardous drugs are handled include surface wipe sampling as part of a comprehensive hazardous drug-safe handling program. Surface wipe sampling may be used as a method to characterize potential occupational dermal exposure risk and to evaluate the effectiveness of implemented controls and the overall safety program. New technology, although currently limited in scope, may make wipe sampling for hazardous drugs more routine, less costly, and provide a shorter response time than classical analytical techniques now in use.

  5. Self-assembling peptide amphiphiles and related methods for growth factor delivery

    Science.gov (United States)

    Stupp, Samuel I [Chicago, IL; Donners, Jack J. J. M.; Silva, Gabriel A [Chicago, IL; Behanna, Heather A [Chicago, IL; Anthony, Shawn G [New Stanton, PA

    2009-06-09

    Amphiphilic peptide compounds comprising one or more epitope sequences for binding interaction with one or more corresponding growth factors, micellar assemblies of such compounds and related methods of use.

  6. Comet assay as a human biomonitoring tool: application in occupational exposure to antineoplastic drugs

    Directory of Open Access Journals (Sweden)

    Carina Ladeira

    2015-05-01

    Occupational exposure to antineoplastic drugs is associated with genotoxic effects, although comet assay analyzed parameters were higher in exposed comparing with controls, were not significant. Also the study of the susceptibility biomarkers did not show statistical significant differences, the small size of our sample hampered the finding of a possible association, let alone a causality relationship.

  7. Driving forces for adsorption of amphiphilic peptides to the air-water interface.

    Science.gov (United States)

    Engin, Ozge; Villa, Alessandra; Sayar, Mehmet; Hess, Berk

    2010-09-02

    We have studied the partitioning of amphiphilic peptides at the air-water interface. The free energy of adsorption from bulk to interface was calculated by determining the potential of mean force via atomistic molecular dynamics simulations. To this end a method is introduced to restrain or constrain the center of mass of a group of molecules in a periodic system. The model amphiphilic peptides are composed of alternating valine and asparagine residues. The decomposition of the free energy difference between the bulk and interface is studied for different peptide block lengths. Our analysis revealed that for short amphiphilic peptides the surface driving force dominantly stems from the dehydration of hydrophobic side chains. The only opposing force is associated with the loss of orientational freedom of the peptide at the interface. For the peptides studied, the free energy difference scales linearly with the size of the molecule, since the peptides mainly adopt extended conformations both in bulk and at the interface. The free energy difference depends strongly on the water model, which can be rationalized through the hydration thermodynamics of hydrophobic solutes. Finally, we measured the reduction of the surface tension associated with complete coverage of the interface with peptides.

  8. 77 FR 41190 - Revised Document Posted: NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare...

    Science.gov (United States)

    2012-07-12

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention [Docket Number NIOSH-190] Revised Document Posted: NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings 2012, Correction AGENCY: National Institute for Occupational Safety and Health (NIOSH) of the...

  9. Inhibition of cardiac inward rectifier currents by cationic amphiphilic drugs.

    Science.gov (United States)

    van der Heyden, M A G; Stary-Weinzinger, A; Sanchez-Chapula, J A

    2013-09-01

    Cardiac inward rectifier channels belong to three different classes of the KIR channel protein family. The KIR2.x proteins generate the classical inward rectifier current, IK1, while KIR3 and KIR6 members are responsible for the acetylcholine responsive and ATP sensitive inward rectifier currents IKAch and IKATP, respectively. Aberrant function of these channels has been correlated with severe cardiac arrhythmias, indicating their significant contribution to normal cardiac electrophysiology. A common feature of inward rectifier channels is their dependence on the lipid phosphatidyl-4,5-bisphospate (PIP2) interaction for functional activity. Cationic amphiphilic drugs (CADs) are one of the largest classes of pharmaceutical compounds. Several widely used CADs have been associated with inward rectifier current disturbances, and recent evidence points to interference of the channel-PIP2 interaction as the underlying mechanism of action. Here, we will review how six of these well known drugs, used for treatment in various different conditions, interfere in cardiac inward rectifier functioning. In contrast, KIR channel inhibition by the anionic anesthetic thiopental is achieved by a different mechanism of channel-PIP2 interference. We will discuss the latest basic science insights of functional inward rectifier current characteristics, recently derived KIR channel structures and specific PIP2-receptor interactions at the molecular level and provide insight in how these drugs interfere in the structure-function relationships.

  10. Synthesis, Characterization, and Aqueous Lubricating Properties of Amphiphilic Graft Copolymers Comprising 2-Methoxyethyl Acrylate

    DEFF Research Database (Denmark)

    Javakhishvili, Irakli; Røn, Troels; Jankova Atanasova, Katja

    2014-01-01

    Amphiphilic anionic and cationic graft copolymers possessing poly(2-hydroxyethyl methacrylate) (PHEMA) backbone and poly(methacrylic acid), poly(2-methoxyethyl acrylate-co-methacrylic acid), and poly(2-methoxyethyl acrylate-co-2-(dimethylamino)ethyl methacrylate) grafts are constructed by merging...... of the corresponding monomers followed by deblocking reaction leads to well-defined amphiphiles with narrow molecular weight distributions (PDI ≤ 1.29) and varying content of methacrylic acid. The graft copolymers showed effective surface adsorption and lubrication for self-mated poly(dimethylsiloxane) (PDMS) contacts...

  11. Chromosomal damage among medical staff occupationally exposed to volatile anesthetics, antineoplastic drugs, and formaldehyde

    Czech Academy of Sciences Publication Activity Database

    Mušák, L.; Šmerhovský, Z.; Halásová, E.; Osina, O.; Letková, L.; Vodičková, Ludmila; Poláková, Veronika; Buchancová, J.; Hemminki, K.; Vodička, Pavel

    2013-01-01

    Roč. 39, č. 6 (2013), s. 618-630 ISSN 0355-3140 Grant - others:MŠVV(SK) 26220220111; UK(SK) 1/0576/10 VEGA; MZd(SK) 2007/48-UK-13; GA MŠMT(CZ) Prvouk-P27/LF1/1 Institutional support: RVO:68378041 Keywords : anesthesiologist * antineoplastic drug * chromosomal aberration Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.095, year: 2013

  12. Additions of caffeic acid, ascorbyl palmitate or gamma-tocopherol to fish oil-enriched energy bars affect lipid oxidation differently

    DEFF Research Database (Denmark)

    Horn, Anna Frisenfeldt; Nielsen, Nina Skall; Jacobsen, Charlotte

    2009-01-01

    The objectives of the study were to investigate the effects of caffeic acid, ascorbyl palmitate and gamma-tocopherol on protection of fish oil-enriched energy bars against lipid oxidation during storage for 10 weeks at room temperature. The lipophilic gamma-tocopherol reduced lipid oxidation during...... storage when added at a concentration above 440 mu g/g fish oil. However, the best antioxidative effect was observed when it was added at a concentration of 660 mu g/g fish oil. In contrast, prooxidative effects were observed when using either gamma-tocopherol at concentrations below 220 mu g/g fish oil......, or the hydrophilic caffeic acid, or the amphiphilic ascorbyl palmitate at concentrations of 75, 150 and 300 mu g/g fish oil. Prooxidative effects were observed as an increase in the formation of lipid hydroperoxides and volatile secondary oxidation products, as well as the development of rancid off...

  13. Fragrance compounds and amphiphilic association structures.

    Science.gov (United States)

    Friberg, S E

    1998-05-01

    Fragrance formulations have traditionally been based on alcohol as the solvent, but the recent legal restrictions on volatile organic solvents have prompted the industry to change to aqueous solubilized systems. The article reviews the fundamental factors in the application of such systems evaluating the influence by different amphiphilic association structures on the vapor pressure of fragrance compounds. This information is subsequently used to estimate the variation of fragrance compound vapor pressures during evaporation. The results reveal that the vapor pressure versus time variation is improved compared to solvent-based formulations.

  14. Molecular biomonitoring of a population of nurses handling antineoplastic drugs

    Energy Technology Data Exchange (ETDEWEB)

    Cornetta, Tommaso [Department of Biology, ' Roma Tre' University, Viale Guglielmo Marconi, 446-00146 Rome (Italy); ' Don Carlo Gnocchi' Foundation, Rome (Italy); Padua, Luca [' Don Carlo Gnocchi' Foundation, Rome (Italy); Department of Neuroscience, Neurology Institute, Catholic University, Rome (Italy); Testa, Antonella; Ievoli, Elena [Toxicology and Biomedical Sciences Section, ENEA Research Center, Casaccia (Rome) (Italy); Festa, Fabiola [Department of Biology, ' Roma Tre' University, Viale Guglielmo Marconi, 446-00146 Rome (Italy); Tranfo, Giovanna [Department of Occupational Hygiene, Italian Institute for Occupational Prevention and Safety, Monteporzio Catone (Rome) (Italy); Baccelliere, Luigi [S. Martino Hospital, Genova (Italy); Cozzi, Renata [Department of Biology, ' Roma Tre' University, Viale Guglielmo Marconi, 446-00146 Rome (Italy)], E-mail: cozzi@bio.uniroma3.it

    2008-02-01

    Many antineoplastic drugs have been found to have carcinogenic, mutagenic and teratogenic activity and so hospital personnel handling these substances are potentially exposed to health risk. Understanding this risk derived from protracted occupational exposure has great relevance even if the workers normally adopt individual and environmental protective measures. To address this question we have studied the presence of DNA and chromosome damage in a population of nurses employed in Italian oncology units and in matched controls. We used the comet assay to evidence the presence of DNA strand breaks, due to both acute and chronic exposure, and the micronucleus (MN) test, which is a measure of clastogenic and aneugenic events. Furthermore, since the individual response to the exogenous insults may be genetically determined, we studied the possible influence of single nucleotide polymorphism in XRCC1 and XRCC3 DNA repair genes on induced genetic damage. We also considered the effects of confounding factors like smoking, age and gender. The results indicated that the exposed subjects had significantly high levels of genetic damage. Age and gender were associated with increased values in MN, both in control and in exposed groups; the smoking habit affects MN frequency in controls, but not in workers. Furthermore we found that exposed subjects bearing at least one XRCC1 variant allele (399Gln) show higher values of MN. The present data provide the evidence to show that occupational exposure to antineoplastic drugs, even if in safety controlled conditions, represents a serious health risk. Furthermore we have shown that the presence of XRCC1 genetic polymorphism could contribute to increase the genetic damage in susceptible individuals who are occupationally exposed to dangerous substances.

  15. Molecular biomonitoring of a population of nurses handling antineoplastic drugs

    International Nuclear Information System (INIS)

    Cornetta, Tommaso; Padua, Luca; Testa, Antonella; Ievoli, Elena; Festa, Fabiola; Tranfo, Giovanna; Baccelliere, Luigi; Cozzi, Renata

    2008-01-01

    Many antineoplastic drugs have been found to have carcinogenic, mutagenic and teratogenic activity and so hospital personnel handling these substances are potentially exposed to health risk. Understanding this risk derived from protracted occupational exposure has great relevance even if the workers normally adopt individual and environmental protective measures. To address this question we have studied the presence of DNA and chromosome damage in a population of nurses employed in Italian oncology units and in matched controls. We used the comet assay to evidence the presence of DNA strand breaks, due to both acute and chronic exposure, and the micronucleus (MN) test, which is a measure of clastogenic and aneugenic events. Furthermore, since the individual response to the exogenous insults may be genetically determined, we studied the possible influence of single nucleotide polymorphism in XRCC1 and XRCC3 DNA repair genes on induced genetic damage. We also considered the effects of confounding factors like smoking, age and gender. The results indicated that the exposed subjects had significantly high levels of genetic damage. Age and gender were associated with increased values in MN, both in control and in exposed groups; the smoking habit affects MN frequency in controls, but not in workers. Furthermore we found that exposed subjects bearing at least one XRCC1 variant allele (399Gln) show higher values of MN. The present data provide the evidence to show that occupational exposure to antineoplastic drugs, even if in safety controlled conditions, represents a serious health risk. Furthermore we have shown that the presence of XRCC1 genetic polymorphism could contribute to increase the genetic damage in susceptible individuals who are occupationally exposed to dangerous substances

  16. Langmuir monolayer formation of metal complexes from polymerizable amphiphilic ligands

    NARCIS (Netherlands)

    Werkman, P.J; Schouten, A.J.

    1996-01-01

    The monolayer behaviour of 4-(10,12-pentacosadiynoicamidomethyl)-pyridine at the air-water interface was studied by measuring the surface pressure-area isotherms. The amphiphile formed stable monolayers with a clear liquid-expanded (LE) to liquid-condensed phase transition at various temperatures.

  17. Improved glucose-neopentyl glycol (GNG) amphiphiles for membrane protein solubilization and stabilization.

    Science.gov (United States)

    Cho, Kyung Ho; Bae, Hyoung Eun; Das, Manabendra; Gellman, Samuel H; Chae, Pil Seok

    2014-02-01

    Membrane proteins are inherently amphipathic and undergo dynamic conformational changes for proper function within native membranes. Maintaining the functional structures of these biomacromolecules in aqueous media is necessary for structural studies but difficult to achieve with currently available tools, thus necessitating the development of novel agents with favorable properties. This study introduces several new glucose-neopentyl glycol (GNG) amphiphiles and reveals some agents that display favorable behaviors for the solubilization and stabilization of a large, multi-subunit membrane protein assembly. Furthermore, a detergent structure-property relationship that could serve as a useful guideline for the design of novel amphiphiles is discussed. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Terpene and dextran renewable resources for the synthesis of amphiphilic biopolymers.

    Science.gov (United States)

    Alvès, Marie-Hélène; Sfeir, Huda; Tranchant, Jean-François; Gombart, Emilie; Sagorin, Gilles; Caillol, Sylvain; Billon, Laurent; Save, Maud

    2014-01-13

    The present work shows the synthesis of amphiphilic polymers based on the hydrophilic dextran and the hydrophobic terpenes as renewable resources. The first step concerns the synthesis of functional terpene molecules by thiol-ene addition chemistry involving amino or carboxylic acid thiols and dihydromyrcenol terpene. The terpene-modified polysaccharides were subsequently synthesized by coupling the functional terpenes with dextran. A reductive amination step produced terpene end-modified dextran with 94% of functionalization, while the esterification step produced three terpene-grafted dextrans with a number of terpene units per dextran of 1, 5, and 10. The amphiphilic renewable grafted polymers were tested as emulsifiers for the stabilization of liquid miniemulsion of terpene droplets dispersed in an aqueous phase. The average hydrodynamic diameter of the stable droplets was observed at about 330 nm.

  19. Intra-chain organisation of hydrophobic residues controls inter-chain aggregation rates of amphiphilic polymers

    Science.gov (United States)

    Varilly, Patrick; Willard, Adam P.; Kirkegaard, Julius B.; Knowles, Tuomas P. J.; Chandler, David

    2017-04-01

    Aggregation of amphiphiles through the action of hydrophobic interactions is a common feature in soft condensed matter systems and is of particular importance in the context of biophysics as it underlies both the generation of functional biological machinery as well as the formation of pathological misassembled states of proteins. Here we explore the aggregation behaviour of amphiphilic polymers using lattice Monte Carlo calculations and show that the distribution of hydrophobic residues within the polymer sequence determines the facility with which dry/wet interfaces can be created and that such interfaces drive the aggregation process.

  20. Physical deposition behavior of stiff amphiphilic polyelectrolytes in an external electric field

    Science.gov (United States)

    Hu, Dongmei; Zuo, Chuncheng; Cao, Qianqian; Chen, Hongli

    2017-08-01

    Coarse-grained molecular dynamics simulations are conducted to study the physical deposition behavior of stiff amphiphilic polyelectrolytes (APEs) in an external electric field. The effects of chain stiffness, the charge distribution of a hydrophilic block, and electric field strength are investigated. Amphiphilic multilayers, which consist of a monolayer of adsorbed hydrophilic monomers (HLMs), a hydrophobic layer, and another hydrophilic layer, are formed in a selective solvent. All cases exhibit locally ordered hydrophilic monolayers. Two kinds of hydrophobic micelles are distinguished based on local structures. Stripe and network hydrophobic patterns are formed in individual cases. Increasing the chain stiffness decreases the thickness of the deposited layer, the lateral size of the hydrophobic micelles, and the amount of deposition. Increasing the number of positively charged HLMs in a single chain has the same effect as increasing chain stiffness. Moreover, when applied normally to the substrate, the electric field compresses the deposited structures and increases the amount of deposition by pulling more PEs toward the substrate. A stronger electric field also facilitates the formation of a thinner and more ordered hydrophilic adsorption layer. These estimates help us explore how to tailor patterned nano-surfaces, nano-interfaces, or amphiphilic nanostructures by physically depositing semi-flexible APEs which is of crucial importance in physical sciences, life sciences and nanotechnology.

  1. Preparation and self-folding of amphiphilic DNA origami.

    Science.gov (United States)

    Zhou, Chao; Wang, Dianming; Dong, Yuanchen; Xin, Ling; Sun, Yawei; Yang, Zhongqiang; Liu, Dongsheng

    2015-03-01

    Amphiphilic DNA origami is prepared by dressing multiple hydrophobic molecules on a rectangular single layer DNA origami, which is then folded or coupled in sandwich-like structures with two outer DNA origami layer and one inner hydrophobic molecules layer. The preference to form different kinds of structures could be tailored by rational design of DNA origami. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. On the slowdown mechanism of water dynamics around small amphiphiles

    NARCIS (Netherlands)

    Homsi Brandeburgo, W.; Thijmen van der Post, S.; Meijer, E.J.; Ensing, B.

    2015-01-01

    Aqueous solvation of small amphiphilic molecules exhibits a unique and complex dynamics, that is only partially understood. A recent series of studies on the hydration of small organic compounds, such as tetramethylurea (TMU), trimethylamine N-oxide (TMAO) and urea, has provided strong evidence of a

  3. Conformational properties of rigid-chain amphiphilic macromolecules : The phase diagram

    NARCIS (Netherlands)

    Markov, V. A.; Vasilevskaya, V. V.; Khalatur, P. G.; ten Brinke, G.; Khokhlov, A. R.

    The coil-globule transition in rigid-chain amphiphilic macromolecules was studied by means of computer simulation, and the phase diagrams for such molecules in the solvent quality-persistence length coordinates were constructed. It was shown that the type of phase diagram depends to a substantial

  4. Self-Assembly of Discrete Metal Complexes in Aqueous Solution via Block Copolypeptide Amphiphiles

    Directory of Open Access Journals (Sweden)

    Timothy J. Deming

    2013-01-01

    Full Text Available The integration of discrete metal complexes has been attracting significant interest due to the potential of these materials for soft metal-metal interactions and supramolecular assembly. Additionally, block copolypeptide amphiphiles have been investigated concerning their capacity for self-assembly into structures such as nanoparticles, nanosheets and nanofibers. In this study, we combined these two concepts by investigating the self-assembly of discrete metal complexes in aqueous solution using block copolypeptides. Normally, discrete metal complexes such as [Au(CN2]−, when molecularly dispersed in water, cannot interact with one another. Our results demonstrated, however, that the addition of block copolypeptide amphiphiles such as K183L19 to [Au(CN2]− solutions induced one-dimensional integration of the discrete metal complex, resulting in photoluminescence originating from multinuclear complexes with metal-metal interactions. Transmission electron microscopy (TEM showed a fibrous nanostructure with lengths and widths of approximately 100 and 20 nm, respectively, which grew to form advanced nanoarchitectures, including those resembling the weave patterns of Waraji (traditional Japanese straw sandals. This concept of combining block copolypeptide amphiphiles with discrete coordination compounds allows the design of flexible and functional supramolecular coordination systems in water.

  5. Improved insulin loading in poly(lactic-co-glycolic) acid (PLGA) nanoparticles upon self-assembly with lipids.

    Science.gov (United States)

    García-Díaz, María; Foged, Camilla; Nielsen, Hanne Mørck

    2015-03-30

    Polymeric nanoparticles are widely investigated as drug delivery systems for oral administration. However, the hydrophobic nature of many polymers hampers effective loading of the particles with hydrophilic macromolecules such as insulin. Thus, the aim of this work was to improve the loading of insulin into poly(lactic-co-glycolic) acid (PLGA) nanoparticles by pre-assembly with amphiphilic lipids. Insulin was complexed with soybean phosphatidylcholine or sodium caprate by self-assembly and subsequently loaded into PLGA nanoparticles by using the double emulsion-solvent evaporation technique. The nanoparticles were characterized in terms of size, zeta potential, insulin encapsulation efficiency and loading capacity. Upon pre-assembly with lipids, there was an increased distribution of insulin into the organic phase of the emulsion, eventually resulting in significantly enhanced encapsulation efficiencies (90% as compared to 24% in the absence of lipids). Importantly, the insulin loading capacity was increased up to 20% by using the lipid-insulin complexes. The results further showed that a main fraction of the lipid was incorporated into the nanoparticles and remained associated to the polymer during release studies in buffers, whereas insulin was released in a non-complexed form as a burst of approximately 80% of the loaded insulin. In conclusion, the protein load in PLGA nanoparticles can be significantly increased by employing self-assembled protein-lipid complexes. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Long-circulating DNA lipid nanocapsules as new vector for passive tumor targeting.

    Science.gov (United States)

    Morille, Marie; Montier, Tristan; Legras, Pierre; Carmoy, Nathalie; Brodin, Priscille; Pitard, Bruno; Benoît, Jean-Pierre; Passirani, Catherine

    2010-01-01

    Systemic gene delivery systems are needed for therapeutic application to organs that are inaccessible by percutaneous injection. Currently, the main objective is the development of a stable and non-toxic vector that can encapsulate and deliver foreign genetic material to target cells. To this end, DNA, complexed with cationic lipids i.e. DOTAP/DOPE, was encapsulated into lipid nanocapsules (LNCs) leading to the formation of stable nanocarriers (DNA LNCs) with a size inferior to 130 nm. Amphiphilic and flexible poly (ethylene glycol) (PEG) polymer coatings [PEG lipid derivative (DSPE-mPEG(2000)) or F108 poloxamer] at different concentrations were selected to make DNA LNCs stealthy. Some of these coated lipid nanocapsules were able to inhibit complement activation and were not phagocytized in vitro by macrophagic THP-1 cells whereas uncoated DNA LNCs accumulated in the vacuolar compartment of THP-1 cells. These results correlated with a significant increase of in vivo circulation time in mice especially for DSPE-mPEG(2000) 10 mm and an early half-life time (t(1/2) of distribution) 5-fold greater than for non-coated DNA LNCs (7.1 h vs 1.4 h). Finally, a tumor accumulation assessed by in vivo fluorescence imaging system was evidenced for these coated LNCs as a passive targeting without causing any hepatic damage.

  7. Polysarcosine-Based Lipids: From Lipopolypeptoid Micelles to Stealth-Like Lipids in Langmuir Blodgett Monolayers

    Directory of Open Access Journals (Sweden)

    Benjamin Weber

    2016-12-01

    Full Text Available Amphiphiles and, in particular, PEGylated lipids or alkyl ethers represent an important class of non-ionic surfactants and have become key ingredients for long-circulating (“stealth” liposomes. While poly-(ethylene glycol (PEG can be considered the gold standard for stealth-like materials, it is known to be neither a bio-based nor biodegradable material. In contrast to PEG, polysarcosine (PSar is based on the endogenous amino acid sarcosine (N-methylated glycine, but has also demonstrated stealth-like properties in vitro, as well as in vivo. In this respect, we report on the synthesis and characterization of polysarcosine based lipids with C14 and C18 hydrocarbon chains and their end group functionalization. Size exclusion chromatography (SEC and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS analysis reveals that lipopeptoids with a degree of polymerization between 10 and 100, dispersity indices around 1.1, and the absence of detectable side products are directly accessible by nucleophilic ring opening polymerization (ROP. The values for the critical micelle concentration for these lipopolymers are between 27 and 1181 mg/L for the ones with C18 hydrocarbon chain or even higher for the C14 counterparts. The lipopolypeptoid based micelles have hydrodynamic diameters between 10 and 25 nm, in which the size scales with the length of the PSar block. In addition, C18PSar50 can be incorporated in 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC monolayers up to a polymer content of 3%. Cyclic compression and expansion of the monolayer showed no significant loss of polymer, indicating a stable monolayer. Therefore, lipopolypeptoids can not only be synthesized under living conditions, but my also provide a platform to substitute PEG-based lipopolymers as excipients and/or in lipid formulations.

  8. Compartmentalization Technologies via Self-Assembly and Cross-Linking of Amphiphilic Random Block Copolymers in Water.

    Science.gov (United States)

    Matsumoto, Mayuko; Terashima, Takaya; Matsumoto, Kazuma; Takenaka, Mikihito; Sawamoto, Mitsuo

    2017-05-31

    Orthogonal self-assembly and intramolecular cross-linking of amphiphilic random block copolymers in water afforded an approach to tailor-make well-defined compartments and domains in single polymer chains and nanoaggregates. For a double compartment single-chain polymer, an amphiphilic random block copolymer bearing hydrophilic poly(ethylene glycol) (PEG) and hydrophobic dodecyl, benzyl, and olefin pendants was synthesized by living radical polymerization (LRP) and postfunctionalization; the dodecyl and benzyl units were incorporated into the different block segments, whereas PEG pendants were statistically attached along a chain. The copolymer self-folded via the orthogonal self-assembly of hydrophobic dodecyl and benzyl pendants in water, followed by intramolecular cross-linking, to form a single-chain polymer carrying double yet distinct hydrophobic nanocompartments. A single-chain cross-linked polymer with a chlorine terminal served as a globular macroinitiator for LRP to provide an amphiphilic tadpole macromolecule comprising a hydrophilic nanoparticle and a hydrophobic polymer tail; the tadpole thus self-assembled into multicompartment aggregates in water.

  9. Host-Guest Interaction between Corona[n]arene and Bisquaternary Ammonium Derivatives for Fabricating Supra-Amphiphile.

    Science.gov (United States)

    Zeng, Lingda; Guo, Qing-Hui; Feng, Yuanning; Xu, Jiang-Fei; Wei, Yuhan; Li, Zhibo; Wang, Mei-Xiang; Zhang, Xi

    2017-06-13

    The interactions between a host, water-soluble corona[n]arene (S6-CAP), and a series of guests, bisquaternary ammonium derivatives (CnDAs), in water, were investigated. The host and guest can form 1:1 host-guest complex. Their binding constants decrease as the alkyl length of CnDAs increases, which can be tunable ranging from 10 3 to 10 6 M -1 . The binding processes are mainly entropy-driven, while the enthalpy changes also play an important role in enhancing the host-guest interactions. In addition, a supra-amphiphile was fabricated with S6-CAP and a normal surfactant bearing bisquaternary ammonium (C4R). The S6-CAP·C4R complex forms micellar aggregates in water, and the system possesses better assembling activity and dilution stability than its building block C4R. This study enriches the families of supra-amphiphiles with a new architecture, and employing such a supra-amphiphile in biofunctional materials is highly anticipated.

  10. Interaction of charged amphiphilic drugs with phosphatidylcholine vesicles studied by NMR

    International Nuclear Information System (INIS)

    Eriksson, L.E.G.

    1987-01-01

    Small unilamellar vesicles from egg phosphatidylcholine in NaCl solutions were exposed to some amphiphilic pharmaca. The aromatic drugs (chlorpromazine, dibucaine, tetracaine, imipramine and propranolol) were in their cationic form of the amines. By 1 H- and 31 P-NMR the membrane signals were observed. In particular, the N-methyl choline proton signals were followed upon drug addition. The intrinsic chemical shift difference (0.02 ppm) between the inner (upfield) and outer choline signals was influenced by the drug concentration. Packing properties of the lipid head groups and ring current shift probably contributed. At very high drug concentration, the vesicles are destroyed. A transformation into a micellar state with a high sample viscosity took place in a narrow concentration range of drug. The anion effects of Cl - were studied from the 35 Cl-NMR linewidth at 9.8 and 39.1 MHz. A continuous increase in the signal linewidth followed upon drug addition to the vesicles. Only chlorpromazine produced a broadening in the absence of vesicles (NaCl blank). The linewidth reflected a critical micelle concentration of this drug around 7 mM in 0.1 M NaCl. The 35 Cl-NMR experiments demonstrated the existence of an anionic counterion effect. This phenomenon should be accounted for when quantitatively analysing drug-membrane interactions in electrostatic terms. (Auth.)

  11. Nanoparticles Embedded in Amphiphilic Membranes for Carbon Dioxide Separation and Dehumidification.

    Science.gov (United States)

    Yong, Wai Fen; Ho, Yan Xun; Chung, Tai-Shung

    2017-10-23

    Polymers containing ethylene oxide (EO) groups have gained significant interest as the EO groups have favorable interactions with polar molecules such as H 2 O, quadrupolar molecules such as CO 2 , and metal ions. However, the main challenges of poly(ethylene oxide) (PEO) membranes are their weak mechanical properties and high crystallinity nature. The amphiphilic copolymer made from PEO terephthalate and poly(butylene terephthalate) (PEOT/PBT) comprises both hydrophilic and hydrophobic segments. The hydrophilic PEOT segment is thermosensitive, which facilities gas transports whereas the hydrophobic PBT segment is rigid, which provides mechanical robustness. This work demonstrates a new strategy to design amphiphilic mixed matrix membranes (MMMs) by incorporating zeolitic imidazolate framework, ZIF-71, into the PEOT/PBT copolymer. The resultant membrane shows an enhanced CO 2 permeability with an ideal CO 2 /N 2 selectivity surpassing the original PEOT/PBT and Robeson's Upper bound line. The nanoparticles-embedded amphiphilic membranes exhibit characteristics of high transparency and mechanical robustness. Mechanically strong composite hollow fiber membranes consisting of PEOT/PBT/ZIF-71 as the selective layer were also prepared. The resultant hollow fibers possess an excellent CO 2 permeance of 131 GPU (gas permeation units), CO 2 /N 2 selectivity of 52.6, H 2 O permeance of 9300 GPU and H 2 O/N 2 selectivity of 3700, showing great potential for industrial CO 2 capture and dehumidification. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Optical characterization of CdS nanoparticles embedded into the comb-type amphiphilic graft copolymer

    Science.gov (United States)

    Kalaycı, Özlem A.; Duygulu, Özgür; Hazer, Baki

    2013-01-01

    This study refers to the synthesis and characterization of a novel organic/inorganic hybrid nanocomposite material containing cadmium sulfide (CdS) nanoparticles. For this purpose, a series of polypropylene (PP)-g-polyethylene glycol (PEG), PP-g-PEG comb-type amphiphilic graft copolymers were synthesized. PEGs with Mn = 400, 2000, 3350, and 8000 Da were used and the graft copolymers obtained were coded as PPEG400, PPEG2000, PPEG3350, and PPEG8000. CdS nanoparticles were formed in tetrahydrofuran solution of PP-g-PEG amphiphilic comb-type copolymer by the reaction between aqueous solutions of Na2S and Cd(CH3COO)2 simultaneously. Micelle formation of PPEG2000 comb-type amphiphilic graft copolymer in both solvent/non-solvent (petroleum ether-THF) by transmission electron microscopy (TEM). The optical characteristics, size morphology, phase analysis, and dispersion of CdS nanoparticles embedded in PPEG400, PPEG2000, PPEG3350, and PPEG8000 comb-type amphiphilic graft copolymer micelles were determined by high resolution TEM (HRTEM), energy dispersive spectroscopy, UV-vis spectroscopy, and fluorescence emission spectroscopy techniques. The aggregate size of PPEG2000-CdS is between 10 and 50 nm; however, in the case of PPEG400-CdS, PPEG3350-CdS, and PPEG8000-CdS samples, it is up to approximately 100 nm. The size of CdS quantum dots in the aggregates for PPEG2000 and PPEG8000 samples was observed as 5 nm by HRTEM analysis, and this result was also supported by UV-vis absorbance spectra and fluorescence emission spectra.

  13. Optical characterization of CdS nanoparticles embedded into the comb-type amphiphilic graft copolymer

    Energy Technology Data Exchange (ETDEWEB)

    Kalayc Latin-Small-Letter-Dotless-I , Oezlem A. [Bulent Ecevit University, Department of Physics (Turkey); Duygulu, Oezguer [TUBITAK Marmara Research Center, Materials Institute (Turkey); Hazer, Baki, E-mail: bkhazer@karaelmas.edu.tr [Bulent Ecevit University, Department of Chemistry (Turkey)

    2013-01-15

    This study refers to the synthesis and characterization of a novel organic/inorganic hybrid nanocomposite material containing cadmium sulfide (CdS) nanoparticles. For this purpose, a series of polypropylene (PP)-g-polyethylene glycol (PEG), PP-g-PEG comb-type amphiphilic graft copolymers were synthesized. PEGs with Mn = 400, 2000, 3350, and 8000 Da were used and the graft copolymers obtained were coded as PPEG400, PPEG2000, PPEG3350, and PPEG8000. CdS nanoparticles were formed in tetrahydrofuran solution of PP-g-PEG amphiphilic comb-type copolymer by the reaction between aqueous solutions of Na{sub 2}S and Cd(CH{sub 3}COO){sub 2} simultaneously. Micelle formation of PPEG2000 comb-type amphiphilic graft copolymer in both solvent/non-solvent (petroleum ether-THF) by transmission electron microscopy (TEM). The optical characteristics, size morphology, phase analysis, and dispersion of CdS nanoparticles embedded in PPEG400, PPEG2000, PPEG3350, and PPEG8000 comb-type amphiphilic graft copolymer micelles were determined by high resolution TEM (HRTEM), energy dispersive spectroscopy, UV-vis spectroscopy, and fluorescence emission spectroscopy techniques. The aggregate size of PPEG2000-CdS is between 10 and 50 nm; however, in the case of PPEG400-CdS, PPEG3350-CdS, and PPEG8000-CdS samples, it is up to approximately 100 nm. The size of CdS quantum dots in the aggregates for PPEG2000 and PPEG8000 samples was observed as 5 nm by HRTEM analysis, and this result was also supported by UV-vis absorbance spectra and fluorescence emission spectra.

  14. Optical characterization of CdS nanoparticles embedded into the comb-type amphiphilic graft copolymer

    International Nuclear Information System (INIS)

    Kalaycı, Özlem A.; Duygulu, Özgür; Hazer, Baki

    2013-01-01

    This study refers to the synthesis and characterization of a novel organic/inorganic hybrid nanocomposite material containing cadmium sulfide (CdS) nanoparticles. For this purpose, a series of polypropylene (PP)-g-polyethylene glycol (PEG), PP-g-PEG comb-type amphiphilic graft copolymers were synthesized. PEGs with Mn = 400, 2000, 3350, and 8000 Da were used and the graft copolymers obtained were coded as PPEG400, PPEG2000, PPEG3350, and PPEG8000. CdS nanoparticles were formed in tetrahydrofuran solution of PP-g-PEG amphiphilic comb-type copolymer by the reaction between aqueous solutions of Na 2 S and Cd(CH 3 COO) 2 simultaneously. Micelle formation of PPEG2000 comb-type amphiphilic graft copolymer in both solvent/non-solvent (petroleum ether–THF) by transmission electron microscopy (TEM). The optical characteristics, size morphology, phase analysis, and dispersion of CdS nanoparticles embedded in PPEG400, PPEG2000, PPEG3350, and PPEG8000 comb-type amphiphilic graft copolymer micelles were determined by high resolution TEM (HRTEM), energy dispersive spectroscopy, UV–vis spectroscopy, and fluorescence emission spectroscopy techniques. The aggregate size of PPEG2000-CdS is between 10 and 50 nm; however, in the case of PPEG400-CdS, PPEG3350-CdS, and PPEG8000-CdS samples, it is up to approximately 100 nm. The size of CdS quantum dots in the aggregates for PPEG2000 and PPEG8000 samples was observed as 5 nm by HRTEM analysis, and this result was also supported by UV–vis absorbance spectra and fluorescence emission spectra.

  15. Enhanced Topical and Transdermal Delivery of Antineoplastic and Antiviral Acyclic Nucleoside Phosphonate cPr-PMEDAP

    Czech Academy of Sciences Publication Activity Database

    Vávrová, K.; Kovaříková, P.; Školová, B.; Líbalová, M.; Roh, J.; Čáp, R.; Holý, Antonín; Hrabálek, A.

    2011-01-01

    Roč. 28, č. 12 (2011), s. 3105-3115 ISSN 0724-8741 R&D Projects: GA MŠk 1M0508 Grant - others:GA ČR(CZ) GAP207/11/0365 Institutional research plan: CEZ:AV0Z40550506 Keywords : acyclic nucleoside phosphonates * antivirals * antineoplastics * permeation enhancer * topical skin application * transdermal delivery Subject RIV: CC - Organic Chemistry Impact factor: 4.093, year: 2011

  16. Cylindrical micelles of a POSS amphiphilic dendrimer as nano-reactors for polymerization.

    Science.gov (United States)

    Weng, Jing-Ting; Yeh, Tso-Fan; Samuel, Ashok Zachariah; Huang, Yi-Fan; Sie, Jyun-Hao; Wu, Kuan-Yi; Peng, Chi-How; Hamaguchi, Hiro-O; Wang, Chien-Lung

    2018-02-15

    A low generation amphiphilic dendrimer, POSS-AD, which has a POSS core and eight amphiphilic arms, was synthesized and used as a nano-reactor to produce well-defined polymer nano-cylinders. Confirmed by small-angle X-ray scattering (SAXS), Raman and NMR spectrometry, monodispersed cylindrical micelles that contain a hydrophilic cavity with a diameter of 2.09 nm and a length of 4.26 nm were produced via co-assembling POSS-AD with hydrophilic liquids, such as H 2 O and HEMA in hydrophobic solvents. Taking the HEMA/POSS-AD cylindrical micelles as nano-reactors, polymerization of HEMA within the micelles results in polymer nano-cylinders (POSS-ADNPs) with a diameter of 2.24 nm and a length of 5.02 nm. The study confirmed that despite the inability to maintain specific shape in solution, low generation dendrimers form well-defined nano-containers or nano-reactors, which relies on co-assembling with hydrophilic guest molecules. These nano-reactors are robust enough to maintain their shape during the polymerization of the guest molecules. Polymer nano-cylinders with dimensions less than 10 nm can thus be produced from the HEMA/POSS-AD micelles. Since the chemical structure of low-generation dendrimers and the contents of the co-assembled nano-reactors can be easily adjusted, the concept holds the potential for the further developments of low-generation amphiphilic dendrimers.

  17. Amphiphilic carbon dots for sensitive detection, intracellular imaging of Al{sup 3+}

    Energy Technology Data Exchange (ETDEWEB)

    Kong, Depeng [State Key Laboratory of Separation Membranes and Membrane Processes, School of Environmental and Chemical Engineering, Tianjin Polytechnic University, Tianjin 300387 (China); Yan, Fanyong, E-mail: yanfanyong@tjpu.edu.cn [State Key Laboratory of Separation Membranes and Membrane Processes, School of Environmental and Chemical Engineering, Tianjin Polytechnic University, Tianjin 300387 (China); Luo, Yunmei [Department of Pharmacology/Key Laboratory for Basic Pharmacology of Ministry of Education, Zunyi Medical College, Guizhou 563000 (China); Ye, Qianghua; Zhou, Siyushan [State Key Laboratory of Separation Membranes and Membrane Processes, School of Environmental and Chemical Engineering, Tianjin Polytechnic University, Tianjin 300387 (China); Chen, Li, E-mail: Chenlis@tjpu.edu.cn [State Key Laboratory of Separation Membranes and Membrane Processes, School of Environmental and Chemical Engineering, Tianjin Polytechnic University, Tianjin 300387 (China)

    2017-02-08

    In this paper, a simple and effective method was designed to synthesize hydrophobic carbon dots. Subsequently, amphiphilic fluorescent carbon dots (A-CDs) were synthesized by further surface modification. The result A-CDs show excellent optical properties with a quantum yield of 16.9%. It was interestingly found that morin (MR) and its fluorescent metal-ion complex (MR-Al{sup 3+}) can successfully coordinate on the surface of A-CDs, the emission of A-CDs completely overlapped the absorption peak of MR-Al{sup 3+}. Thus, the prepared A-CDs can be used as an effective fluorescent probe for Al{sup 3+} based on a fluorescence resonance energy transfer process. The sensing platform can realize real-time detection of Al{sup 3+} within 0.5 min. The fluorescence signals of the system were linearly correlated with the concentration of Al{sup 3+} over a range of 8–20 μM, with a detection limit of 0.113 μM. The method was also successfully applied to image the distribution of Al{sup 3+} in Human Umbilical Vein Endothelial Cells. - Highlights: • Amphiphilic carbon dots were obtained by simply modifying hydrophobic carbon dots. • Amphiphilic carbon dots/morin-Al{sup 3+} was used as a selective turn-on probe for Al{sup 3+}. • The method was employed to intracellular imaging Al{sup 3+} in living cells.

  18. Liposomal photosensitizers: potential platforms for anticancer photodynamic therapy

    Directory of Open Access Journals (Sweden)

    L.A. Muehlmann

    2011-08-01

    Full Text Available Photodynamic therapy is a well-established and clinically approved treatment for several types of cancer. Antineoplastic photodynamic therapy is based on photosensitizers, i.e., drugs that absorb photons translating light energy into a chemical potential that damages tumor tissues. Despite the encouraging clinical results with the approved photosensitizers available today, the prolonged skin phototoxicity, poor selectivity for diseased tissues, hydrophobic nature, and extended retention in the host organism shown by these drugs have stimulated researchers to develop new formulations for photodynamic therapy. In this context, due to their amphiphilic characteristic (compatibility with both hydrophobic and hydrophilic substances, liposomes have proven to be suitable carriers for photosensitizers, improving the photophysical properties of the photosensitizers. Moreover, as nanostructured drug delivery systems, liposomes improve the efficiency and safety of antineoplastic photodynamic therapy, mainly by the classical phenomenon of extended permeation and retention. Therefore, the association of photosensitizers with liposomes has been extensively studied. In this review, both current knowledge and future perspectives on liposomal carriers for antineoplastic photodynamic therapy are critically discussed.

  19. Amphiphile Meets Amphiphile: Beyond the Polar-Apolar Dualism in Ionic Liquid/Alcohol Mixtures.

    Science.gov (United States)

    Russina, Olga; Sferrazza, Alessio; Caminiti, Ruggero; Triolo, Alessandro

    2014-05-15

    The mesoscopic morphology of binary mixtures of ethylammonium nitrate (EAN), the protic ionic liquid par excellence, and methanol is explored using neutron/X-ray diffraction and computational techniques. Both compounds are amphiphilic and characterized by an extended hydrogen bonding network: surprisingly, though macroscopically homogeneous, these mixtures turn out to be mesoscopically highly heterogeneous. Our study reveals that even in methanol-rich mixtures, a wide distribution of clusters exists where EAN preserves its bulk, sponge-like morphology. Accordingly methanol does not succeed in fully dissociating the ionic liquid that keeps on organizing in a bulk-like fashion. This behavior represents the premises to the more dramatic phenomenology observed with longer alcohols that eventually phase separate from EAN. These results challenge the commonly accepted polar and apolar moieties segregation in ionic liquids/molecular liquids mixtures and the current understanding of technologically relevant solvation processes.

  20. Applications of lipid nanocarriers for solid tumors therapy: literature review; Aplicacoes das nanoparticulas lipidicas no tratamento de tumores solidos: revisao de literatura

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, Lidiane Correia de; Souza, Leonardo Gomes; Marreto, Ricardo Neves; Lima, Eliana Martins; Taveira, Stephania Fleury [Universidade Federal de Goias (UFG), Goiania, GO (Brazil). Fac. de Farmacia; Taveira, Eliseu Jose Fleury, E-mail: stephaniafleury@gmail.com [Hospital Erasto Gaertner, Curitiba, PR (Brazil). Oncologia Clinica

    2012-07-01

    Introduction: Lipid nanocarriers are systems used to target drugs to its site of action and have attracted attention of the scientific community because they are biocompatible and biodegradable. These systems can target drugs to solid tumors, providing sustained drug release in the site of action, thus increasing the utility of the antineoplastic chemotherapy. Objective: To review the available literature on in vivo experiments with lipid nanocarriers containing cytotoxic drugs for solid tumors treatment. Method: A search study was carried out in Pubmed{sup R} database from 2007 to 2011, with subject descriptors: liposomes, lipid nanoparticles, cancer and in vivo, with the boolean operator 'and' among them, in English. Results: 1,595 papers related to the use of liposomes and 77 related to lipid nanoparticles were found. Few studies reported in vivo experiments with lipid nanoparticles (28 papers) compared to liposomes (472 papers), since liposomes were developed two decades before lipid nanoparticles. Four liposomal medicines have already been approved and are used in the clinic while only one medicine containing lipid nanoparticles is in phase I of clinical studies. Conclusion: The number of papers related to the use of nanotechnology for cancer treatment is increasing rapidly, making important to know the different kinds of nanocarriers and, especially, those which are already used in the clinic. There are only few clinical studies on lipid nanocarriers; however, these systems present an enormous potential to improve the clinical practice in oncology. (author)

  1. Design and application of cationic amphiphilic β-cyclodextrin derivatives as gene delivery vectors

    Science.gov (United States)

    Wan, Ning; Huan, Meng-Lei; Ma, Xi-Xi; Jing, Zi-Wei; Zhang, Ya-Xuan; Li, Chen; Zhou, Si-Yuan; Zhang, Bang-Le

    2017-11-01

    The nano self-assembly profiles of amphiphilic gene delivery vectors could improve the density of local cationic head groups to promote their DNA condensation capability and enhance the interaction between cell membrane and hydrophobic tails, thus increasing cellular uptake and gene transfection. In this paper, two series of cationic amphiphilic β-cyclodextrin (β-CD) derivatives were designed and synthesized by using 6-mono-OTs-β-CD (1) as the precursor to construct amphiphilic gene vectors with different building blocks in a selective and controlled manner. The effect of different type and degree of cationic head groups on transfection and the endocytic mechanism of β-CD derivatives/DNA nanocomplexes were also investigated. The results demonstrated that the designed β-cyclodextrin derivatives were able to compact DNA to form stable nanocomplexes and exhibited low cytotoxicity. Among them, PEI-1 with PEI head group showed enhanced transfection activity, significantly higher than commercially available agent PEI25000 especially in the presence of serum, showing potential application prospects in clinical trials. Moreover, the endocytic uptake mechanism involved in the gene transfection of PEI-1 was mainly through caveolae-mediated endocytosis, which could avoid the lysosomal degradation of loaded gene, and had great importance for improving gene transfection activity.

  2. New penta-saccharide-bearing tripod amphiphiles for membrane protein structure studies

    DEFF Research Database (Denmark)

    Ehsan, Muhammad; Ghani, Lubna; Du, Yang

    2017-01-01

    of detergents, are available, purification and structural characterization of many membrane proteins remain challenging. In the current study, a new class of tripod amphiphiles bearing two different penta-saccharide head groups, designated TPSs, were developed and evaluated for their ability to extract...

  3. Direct investigation of the vectorization properties of amphiphilic cyclodextrins in phospholipid films.

    Science.gov (United States)

    Javierre, Isabelle; Nedyalkov, Mickael; Petkova, Vera; Benattar, Jean Jacques; Weisse, Sandrine; Auzély-Velty, Rachel; Djedaïni-Pilard, Florence; Perly, Bruno

    2002-10-01

    Recently, new cyclodextrin derivatives were synthesized and shown to exhibit strong amphiphilic properties. In this paper, we study the action of these new amphiphilic cyclodextrins on phospholipids. Mixed phospholipid/cyclodextrin derivative films were prepared and studied using X-ray reflectivity for various phospholipid/cyclodextrin ratios. A molar ratio of 3 provides a highly stable film the molecular structure of which has been investigated in detail. The cholesterol tail of the cyclodextrin molecule was found to be anchored into the phospholipid film. The cyclodextrin moieties exposed to the aqueous medium are prone to the addition of the guest molecule Dosulepin, making them of high interest for drug delivery. For this purpose and as an example of a potential application, this cyclodextrin molecular carrier property is also addressed to this complex film architecture.

  4. A Water-Soluble Cyclotriveratrylene-Based Supra-amphiphile: Synthesis, pH-Responsive Self-Assembly in Water, and Its Application in Controlled Drug Release.

    Science.gov (United States)

    Xia, Danyu; Li, Yang; Jie, Kecheng; Shi, Bingbing; Yao, Yong

    2016-06-17

    A new water-soluble cyclotriveratrylene (WCTV) was designed and synthesized, and benzyldimethyldodecylammonium chloride (G) was chosen as the guest molecule to construct a supra-amphiphile by the host-guest interaction between WCTV and G in water, which is pH responsive. The supra-amphiphiles self-assembled into vesicles in water. When the pH of the solution was below 7.0, the supra-amphiphile disassociated, and the vesicles collapsed. Then, the pH-responsive self-assembly system was utilized for controlled drug release.

  5. Coassembly of Lysozyme and Amphiphilic Biomolecules Driven by Unimer-Aggregate Equilibrium.

    Science.gov (United States)

    Tao, Yuanyuan; Ma, Xiaoteng; Cai, Yaqian; Liu, Li; Zhao, Hanying

    2018-04-12

    Synthesis and self-assembly of bioconjugates composed of proteins and synthetic molecules have been widely studied because of the potential applications in medicine, biotechnology, and nanotechnology. One of the challenging research studies in this area is to develop organic solvent-free approaches to the synthesis and self-assembly of amphiphilic bioconjugates. In this research, dialysis-assisted approach, a method based on unimer-aggregate equilibrium, was applied in the coassembly of lysozyme and conjugate of cholesterol and glutathione (Ch-GSH). In phosphate buffer solution, amphiphilic Ch-GSH conjugate self-assembles into vesicles, and the vesicle solution is dialyzed against lysozyme solution. Negatively charged Ch-GSH unimers produced in the unimer-vesicle exchange equilibrium, diffuse across the dialysis membrane and have electrostatic interaction with positively charged lysozyme, resulting in the formation of Ch-GSH-lysozyme bioconjugate. Above a critical concentration, the three-component bioconjugate molecules self-assemble into bioactive vesicles.

  6. A theoretical study of colloidal forces near an amphiphilic polymer brush

    Science.gov (United States)

    Wu, Jianzhong

    2011-03-01

    Polymer-based ``non-stick'' coatings are promising as the next generation of effective, environmentally-friendly marine antifouling systems that minimize nonspecific adsorption of extracellular polymeric substances (EPS). However, design and development of such systems are impeded by the poor knowledge of polymer-mediated interactions of biomacromolecules with the protected substrate. In this work, a polymer density functional theory (DFT) is used to predict the potential of mean force between spherical biomacromolecules and amphiphilic copolymer brushes within a coarse-grained model that captures essential nonspecific interactions such as the molecular excluded volume effects and the hydrophobic energies. The relevance of theoretical results for practical control of the EPS adsorption is discussed in terms of the efficiency of different brush configurations to prevent biofouling. It is shown that the most effective antifouling surface may be accomplished by using amphiphilic brushes with a long hydrophilic backbone and a hydrophobic end at moderate grafting density.

  7. HPMA-based block copolymers promote differential drug delivery kinetics for hydrophobic and amphiphilic molecules.

    Science.gov (United States)

    Tomcin, Stephanie; Kelsch, Annette; Staff, Roland H; Landfester, Katharina; Zentel, Rudolf; Mailänder, Volker

    2016-04-15

    We describe a method how polymeric nanoparticles stabilized with (2-hydroxypropyl)methacrylamide (HPMA)-based block copolymers are used as drug delivery systems for a fast release of hydrophobic and a controlled release of an amphiphilic molecule. The versatile method of the miniemulsion solvent-evaporation technique was used to prepare polystyrene (PS) as well as poly-d/l-lactide (PDLLA) nanoparticles. Covalently bound or physically adsorbed fluorescent dyes labeled the particles' core and their block copolymer corona. Confocal laser scanning microscopy (CLSM) in combination with flow cytometry measurements were applied to demonstrate the burst release of a fluorescent hydrophobic drug model without the necessity of nanoparticle uptake. In addition, CLSM studies and quantitative calculations using the image processing program Volocity® show the intracellular detachment of the amphiphilic block copolymer from the particles' core after uptake. Our findings offer the possibility to combine the advantages of a fast release for hydrophobic and a controlled release for an amphiphilic molecule therefore pointing to the possibility to a 'multi-step and multi-site' targeting by one nanocarrier. We describe thoroughly how different components of a nanocarrier end up in cells. This enables different cargos of a nanocarrier having a consecutive release and delivery of distinct components. Most interestingly we demonstrate individual kinetics of distinct components of such a system: first the release of a fluorescent hydrophobic drug model at contact with the cell membrane without the necessity of nanoparticle uptake. Secondly, the intracellular detachment of the amphiphilic block copolymer from the particles' core after uptake occurs. This offers the possibility to combine the advantages of a fast release for a hydrophobic substance at the time of interaction of the nanoparticle with the cell surface and a controlled release for an amphiphilic molecule later on therefore

  8. French Health Technology Assessment of Antineoplastic Drugs Indicated in the Treatment of Solid Tumours: Perspective for Future Trends.

    Science.gov (United States)

    Chouaid, Christos; Borget, Isabelle; Braun, Eric; Bazil, Marie-Laure; Schaetz, Dominique; Rémuzat, Cécile; Toumi, Mondher

    2016-08-01

    France is one of the European countries that spend the most on oncology drugs. To keep pharmaceutical expenditure under control, Health Authorities highly scrutinize market access of costly medicines. To assess current and future trends in French health technology assessment (HTA) of antineoplastic drugs indicated in the treatment of solid tumours. A review of the SMR and ASMR drivers of the Transparency Committee (CT) opinions issued for antineoplastic drugs indicated in the treatment of solid tumours and approved between 2009 and 2014 was performed to assess current trends in French health technology assessment (HTA), complemented by an expert board consultation to capture the critical issues on the future of antineoplastic drugs HTA. Thirty-one drugs indicated for the treatment of solid tumours were identified (77 % targeted therapies). Initial CT assessments were available for 26 drugs. Four key items in the CT assessment were identified: 1) Clinical trial methodology; 2) Acceptance of progression-free survival (PFS) as a valuable endpoint; 3) Transferability of clinical trials in clinical practice; 4) Unpredictability of CT decisions. Experts raised the important development of personalised medicines in oncology and key challenges for oncology products to generate information expected from HTA perspective. The French system remains committed to its values and philosophy (access of all innovations for everybody) which are threatened by the increasing launch of innovative therapies and budget constraint. Both HTA decision framework evolution and revision of the current pricing process should be considered in France to cope with these new challenges.

  9. Shape Recovery with Concomitant Mechanical Strengthening of Amphiphilic Shape Memory Polymers in Warm Water

    International Nuclear Information System (INIS)

    Zhang, Ben; DeBartolo, Janae E.; Song, Jie

    2017-01-01

    Maintaining adequate or enhancing mechanical properties of shape memory polymers (SMPs) after shape recovery in an aqueous environment are greatly desired for biomedical applications of SMPs as self-fitting tissue scaffolds or minimally invasive surgical implants. Here we report stable temporary shape fixing and facile shape recovery of biodegradable triblock amphiphilic SMPs containing a poly(ethylene glycol) (PEG) center block and flanking poly(lactic acid) or poly(lactic-co-glycolic acid) blocks in warm water, accompanied with concomitant enhanced mechanical strengths. Differential scanning calorimetry (DSC), wide-angle X-ray diffraction (WXRD) and small-angle X-ray scattering (SAXS) analyses revealed that the unique stiffening of the amphiphilic SMPs upon hydration was due to hydration-driven microphase separation and PEG crystallization. We further demonstrated that the chemical composition of degradable blocks in these SMPs could be tailored to affect the persistence of hydration-induced stiffening upon subsequent dehydration. These properties combined open new horizons for these amphiphilic SMPs for smart weight-bearing in vivo applications (e.g. as self-fitting intervertebral discs). In conclusion, this study also provides a new material design strategy to strengthen polymers in aqueous environment in general.

  10. Self-Assembled Nanocarriers Based on Amphiphilic Natural Polymers for Anti- Cancer Drug Delivery Applications.

    Science.gov (United States)

    Sabra, Sally; Abdelmoneem, Mona; Abdelwakil, Mahmoud; Mabrouk, Moustafa Taha; Anwar, Doaa; Mohamed, Rania; Khattab, Sherine; Bekhit, Adnan; Elkhodairy, Kadria; Freag, May; Elzoghby, Ahmed

    2017-01-01

    Micellization provides numerous merits for the delivery of water insoluble anti-cancer therapeutic agents including a nanosized 'core-shell' drug delivery system. Recently, hydrophobically-modified polysaccharides and proteins are attracting much attention as micelle forming polymers to entrap poorly soluble anti-cancer drugs. By virtue of their small size, the self-assembled micelles can passively target tumor tissues via enhanced permeation and retention effect (EPR). Moreover, the amphiphilic micelles can be exploited for active-targeted drug delivery by attaching specific targeting ligands to the outer micellar hydrophilic surface. Here, we review the conjugation techniques, drug loading methods, physicochemical characteristics of the most important amphiphilic polysaccharides and proteins used as anti-cancer drug delivery systems. Attention focuses on the mechanisms of tumor-targeting and enhanced anti-tumor efficacy of the encapsulated drugs. This review will highlight the remarkable advances of hydrophobized polysaccharide and protein micelles and their potential applications as anti-cancer drug delivery nanosystems. Micellar nanocarriers fabricated from amphiphilic natural polymers hold great promise as vehicles for anti-cancer drugs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  11. Stable isotope-assisted NMR characterization of interaction between lipid A and sarcotoxin IA, a cecropin-type antibacterial peptide

    Energy Technology Data Exchange (ETDEWEB)

    Yagi-Utsumi, Maho [Institute for Molecular Science and Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences, Okazaki 444-8787 (Japan); Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603 (Japan); Yamaguchi, Yoshiki [Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603 (Japan); Advanced Science Institute, RIKEN, Wako 351-0198 (Japan); Boonsri, Pornthip [Institute for Molecular Science and Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences, Okazaki 444-8787 (Japan); Department of Chemistry, Faculty of Science, Kasetsart University, Bangkok 10900 (Thailand); Iguchi, Takeshi [Bioscience Research Laboratory, Fujiya Co., Ltd., Hadano, Kanagawa 257-0031 (Japan); Okemoto, Kazuo [Department of Biochemistry and Cell Biology, National Institute of Infectious Disease, Tokyo 162-8640 (Japan); Natori, Shunji [National Institute of Agrobiological Sciences, Tsukuba 305-8602 (Japan); Kato, Koichi, E-mail: kkatonmr@ims.ac.jp [Institute for Molecular Science and Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences, Okazaki 444-8787 (Japan); Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603 (Japan); The Glycoscience Institute, Ochanomizu University, Tokyo 135-0064 (Japan); GLYENCE Co., Ltd., Nagoya 474-0858 (Japan)

    2013-02-08

    Highlights: ► Recombinant sarcotoxin IA was successfully produced with {sup 13}C- and {sup 15}N-labeling. ► Sarcotoxin IA adopts an N-terminal α-helix upon binding to lipid A-embedding micelles. ► Two lysine residues are involved in lipid A-mediated antibacterial activities. -- Abstract: Sarcotoxin IA is a 39-residue cecropin-type peptide from Sarcophaga peregrina. This peptide exhibits antibacterial activity against Gram-negative bacteria through its interaction with lipid A, a core component of lipopolysaccharides. To acquire detailed structural information on this specific interaction, we performed NMR analysis using bacterially expressed sarcotoxin IA analogs with {sup 13}C- and {sup 15}N-labeling along with lipid A-embedding micelles composed of dodecylphosphocholine. By inspecting the stable isotope-assisted NMR data, we revealed that the N-terminal segment (Leu3–Arg18) of sarcotoxin IA formed an amphiphilic α-helix upon its interaction with the aqueous micelles. Furthermore, chemical shift perturbation data indicated that the amino acid residues displayed on this α-helix were involved in the specific interaction with lipid A. On the basis of these data, we successfully identified Lys4 and Lys5 as key residues in the interaction with lipid A and the consequent antibacterial activity. Therefore, these results provide unique information for designing chemotherapeutics based on antibacterial peptide structures.

  12. Differential Interaction of Synthetic Glycolipids with Biomimetic Plasma Membrane Lipids Correlates with the Plant Biological Response.

    Science.gov (United States)

    Nasir, Mehmet Nail; Lins, Laurence; Crowet, Jean-Marc; Ongena, Marc; Dorey, Stephan; Dhondt-Cordelier, Sandrine; Clément, Christophe; Bouquillon, Sandrine; Haudrechy, Arnaud; Sarazin, Catherine; Fauconnier, Marie-Laure; Nott, Katherine; Deleu, Magali

    2017-09-26

    Natural and synthetic amphiphilic molecules including lipopeptides, lipopolysaccharides, and glycolipids are able to induce defense mechanisms in plants. In the present work, the perception of two synthetic C14 rhamnolipids, namely, Alk-RL and Ac-RL, differing only at the level of the lipid tail terminal group have been investigated using biological and biophysical approaches. We showed that Alk-RL induces a stronger early signaling response in tobacco cell suspensions than does Ac-RL. The interactions of both synthetic RLs with simplified biomimetic membranes were further analyzed using experimental and in silico approaches. Our results indicate that the interactions of Alk-RL and Ac-RL with lipids were different in terms of insertion and molecular responses and were dependent on the lipid composition of model membranes. A more favorable insertion of Alk-RL than Ac-RL into lipid membranes is observed. Alk-RL forms more stable molecular assemblies than Ac-RL with phospholipids and sterols. At the molecular level, the presence of sterols tends to increase the RLs' interaction with lipid bilayers, with a fluidizing effect on the alkyl chains. Taken together, our findings suggest that the perception of these synthetic RLs at the membrane level could be related to a lipid-driven process depending on the organization of the membrane and the orientation of the RLs within the membrane and is correlated with the induction of early signaling responses in tobacco cells.

  13. Using crosslinkable diacetylene phospholipids to construct two-dimensional packed beds in supported lipid bilayer separation platforms

    Directory of Open Access Journals (Sweden)

    Shu-Kai Hu, Sheng-Wen Hsiao, Hsun-Yen Mao, Ya-Ming Chen, Yung Chang and Ling Chao

    2013-01-01

    Full Text Available Separating and purifying cell membrane-associated biomolecules has been a challenge owing to their amphiphilic property. Taking these species out of their native lipid membrane environment usually results in biomolecule degradation. One of the new directions is to use supported lipid bilayer (SLB platforms to separate the membrane species while they are protected in their native environment. Here we used a type of crosslinkable diacetylene phospholipids, diynePC (1,2-bis(10,12-tricosadiynoyl-sn-glycero-3-phosphocholine, as a packed material to create a 'two-dimensional (2D packed bed' in a SLB platform. After the diynePC SLB is exposed to UV light, some of the diynePC lipids in the SLB can crosslink and the non-crosslinked monomer lipids can be washed away, leaving a 2D porous solid matrix. We incorporated the lipid vesicle deposition method with a microfluidic device to pattern the location of the packed-bed region and the feed region with species to be separated in a SLB platform. Our atomic force microscopy result shows that the nano-scaled structure density of the '2D packed bed' can be tuned by the UV dose applied to the diynePC membrane. When the model membrane biomolecules were forced to transport through the packed-bed region, their concentration front velocities were found to decrease linearly with the UV dose, indicating the successful creation of packed obstacles in these 2D lipid membrane separation platforms.

  14. New carbon-carbon linked amphiphilic carboranyl-porphyrins as boron neutron capture agents

    International Nuclear Information System (INIS)

    Vicente, M.G.H.; Wickramasinghe, A.; Shetty, S.J.; Smith, K.M.

    2000-01-01

    Novel amphiphilic carboranyl-porphyrins have been synthesized for Boron Neutron Capture Therapy (BNCT). These compounds have carbon-carbon bonds between the carborane residues and the porphyrin meso-phenyl groups, and contain 28-31% boron by weight . (author)

  15. Block versus Random Amphiphilic Glycopolymer Nanopaticles as Glucose-Responsive Vehicles.

    Science.gov (United States)

    Guo, Qianqian; Zhang, Tianqi; An, Jinxia; Wu, Zhongming; Zhao, Yu; Dai, Xiaomei; Zhang, Xinge; Li, Chaoxing

    2015-10-12

    To explore the effect of polymer structure on their self-assembled aggregates and their unique characteristics, this study was devoted to developing a series of amphiphilic block and random phenylboronic acid-based glycopolymers by RAFT polymerization. The amphiphilic glycopolymers were successfully self-assembled into spherically shaped nanoparticles with narrow size distribution in aqueous solution. For block and random copolymers with similar monomer compositions, block copolymer nanoparticles exhibited a more regular transmittance change with the increasing glucose level, while a more evident variation of size and quicker decreasing tendency in I/I0 behavior in different glucose media were observed for random copolymer nanoparticles. Cell viability of all the polymer nanoparticles investigated by MTT assay was higher than 80%, indicating that both block and random copolymers had good cytocompatibility. Insulin could be encapsulated into both nanoparticles, and insulin release rate for random glycopolymer was slightly quicker than that for the block ones. We speculate that different chain conformations between block and random glycopolymers play an important role in self-assembled nanoaggregates and underlying glucose-sensitive behavior.

  16. Regulation of membrane protein function by lipid bilayer elasticity—a single molecule technology to measure the bilayer properties experienced by an embedded protein

    DEFF Research Database (Denmark)

    Lundbæk, Jens August

    2008-01-01

    , regulate a number of structurally unrelated proteins in an apparently non-specific manner. It is well known that changes in the physical properties of a lipid bilayer (e.g., thickness or monolayer spontaneous curvature) can affect the function of an embedded protein. However, the role of such changes......-dependent sodium channels, N-type calcium channels and GABAA receptors, it has been shown that membrane protein function in living cells can be regulated by amphiphile induced changes in bilayer elasticity. Using the gramicidin channel as a molecular force transducer, a nanotechnology to measure the elastic...... properties experienced by an embedded protein has been developed. A theoretical and technological framework, to study the regulation of membrane protein function by lipid bilayer elasticity, has been established....

  17. Triblock Copolymers with Grafted Fluorine-Free Amphiphilic Non-Ionic Side Chains for Antifouling and Fouling-Release Applications

    Energy Technology Data Exchange (ETDEWEB)

    Y Cho; H Sundaram; C Weinman; M Paik; M Dimitriou; J Finlay; M Callow; J Callow; E Kramer; C Ober

    2011-12-31

    Fluorine-free, amphiphilic, nonionic surface active block copolymers (SABCs) were synthesized through chemical modification of a polystyrene-block-poly(ethylene-ran-butylene)-block-polyisoprene triblock copolymer precursor with selected amphiphilic nonionic Brij and other surfactants. Amphiphilicity was imparted by a hydrophobic aliphatic group combined with a hydrophilic poly(ethylene glycol) (PEG) group-containing moiety. The surfaces were characterized by dynamic water contact angle, atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS), and near edge X-ray absorption fine structure (NEXAFS) analysis. In biofouling assays, settlement (attachment) of both spores of the green alga Ulva and cells of the diatom Navicula on SABCs modified with Brij nonionic side chains was significantly reduced relative to a PDMS standard, with a nonionic surfactant combining a PEG group and an aliphatic moiety demonstrating the best performance. Additionally, a fouling-release assay using sporelings (young plants) of Ulva and Navicula suggested that the SABC derived from nonionic Brij side chains also out-performed PDMS as a fouling-release material. Good antifouling and fouling-release properties were not demonstrated for the other two amphiphilic surfaces derived from silicone and aromatic group containing nonionic surfactants included in this study. The results suggest that small differences in chemical surface functionality impart more significant changes with respect to the antifouling settlement and fouling-release performance of materials than overall wettability behavior.

  18. Synthesis of amphiphilic aminated inulin via 'click chemistry' and evaluation for its antibacterial activity.

    Science.gov (United States)

    Dong, Fang; Zhang, Jun; Yu, Chunwei; Li, Qing; Ren, Jianming; Wang, Gang; Gu, Guodong; Guo, Zhanyong

    2014-09-15

    Inulins are a group of abundant, water-soluble, renewable polysaccharides, which exhibit attractive bioactivities and natural properties. Improvement such as chemical modification of inulin is often performed prior to further utilization. We hereby presented a method to modify inulin at its primary hydroxyls to synthesize amphiphilic aminated inulin via 'click chemistry' to facilitate its chemical manipulation. Additionally, its antibacterial property against Staphylococcus aureus (S. aureus) was also evaluated and the best inhibitory index against S. aureus was 58% at 1mg/mL. As the amphiphilic aminated inulin is easy to prepare and exhibits improved bioactivity, this material may represent as an attractive new platform for chemical modifications of inulin. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Antineoplastic drugs and radiation: comparison of the phenomena determining the effectiveness of fractionated treatments

    International Nuclear Information System (INIS)

    Mauro, F.; Briganti, G.; Nervi, C.

    1983-01-01

    In the last ten years the criteria for effective radiotherapy regimens have been rediscussed by analyzing the dependence of radiation response upon the radiobiological phenomena affecting the results of fractionated treatments. In the original definition of H.R. Withers, these phenomena have been referred to as the four R's of radiotherapy, and today we suspect that their number may be higher than that. By analogy, and in spite of the fact that chemical cytotoxic agents are seldom radiomimetic in the strict sense of the word, a similar general analysis could be used to discuss the effectiveness of fractionated administrations of anti-neoplastic drugs. However, information is only available for the cell-cycle age-dependence of lethal and kinetic effects and the repair from potentially lethal damage induced by these agents. In the present work, an attempt is made to discuss some of the neglected R's of chemotherapy, with the aim of establishing (not exclusively empirical) criteria for drug scheduling and of clarifying some of the observations on interaction between agents. In particular, with regard to antineoplastic drugs, published and unpublished information is available not only for the well-known phenomenon of reassortment, but also for the shape of the survival curve, recovery (or potentiation) between dose fraction, and recruitment. Some advantages (and pitfalls) can be evidenced when applying this kind of radiobiological approach to chemotherapy

  20. Methotrexate diethyl ester-loaded lipid-core nanocapsules in aqueous solution increased antineoplastic effects in resistant breast cancer cell line

    Directory of Open Access Journals (Sweden)

    Yurgel VC

    2014-03-01

    Full Text Available Virginia C Yurgel,1,* Catiuscia P Oliveira,2,* Karine R Begnini,1 Eduarda Schultze,1 Helena S Thurow,1 Priscila MM Leon,1 Odir A Dellagostin,1 Vinicius F Campos,1 Ruy CR Beck,2 Silvia S Guterres,2 Tiago Collares,1 Adriana R Pohlmann,2–4 Fabiana K Seixas11Programa de Pós-Graduação em Biotecnologia (PPGB, Grupo de Pesquisa em Oncologia Celular e Molecular, Laboratório de Genômica Funcional, Biotecnologia/Centro de Desenvolvimento Tecnológico, Universidade Federal de Pelotas, Pelotas, Rio Grande do Sul, Brazil; 2Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; 3Departamento de Química Orgânica, Instituto de Química, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; 4Centro de Nanociência e Nanotecnologia, CNANO-UFRGS, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil*These authors contributed equally to this workAbstract: Breast cancer is the most frequent cancer affecting women. Methotrexate (MTX is an antimetabolic drug that remains important in the treatment of breast cancer. Its efficacy is compromised by resistance in cancer cells that occurs through a variety of mechanisms. This study evaluated apoptotic cell death and cell cycle arrest induced by an MTX derivative (MTX diethyl ester [MTX(OEt2] and MTX(OEt2-loaded lipid-core nanocapsules in two MTX-resistant breast adenocarcinoma cell lines, MCF-7 and MDA-MB-231. The formulations prepared presented adequate granulometric profile. The treatment responses were evaluated through flow cytometry. Relying on the mechanism of resistance, we observed different responses between cell lines. For MCF-7 cells, MTX(OEt2 solution and MTX(OEt2-loaded lipid-core nanocapsules presented significantly higher apoptotic rates than untreated cells and cells incubated with unloaded lipid-core nanocapsules. For MDA-MB-231

  1. Self-assembly of active amphiphilic Janus particles

    Science.gov (United States)

    Mallory, S. A.; Alarcon, F.; Cacciuto, A.; Valeriani, C.

    2017-12-01

    In this article, we study the phenomenology of a two dimensional dilute suspension of active amphiphilic Janus particles. We analyze how the morphology of the aggregates emerging from their self-assembly depends on the strength and the direction of the active forces. We systematically explore and contrast the phenomenologies resulting from particles with a range of attractive patch coverages. Finally, we illustrate how the geometry of the colloids and the directionality of their interactions can be used to control the physical properties of the assembled active aggregates and suggest possible strategies to exploit self-propulsion as a tunable driving force for self-assembly.

  2. Evidence for tankyrases as antineoplastic targets in lung cancer

    International Nuclear Information System (INIS)

    Busch, Alexander M; Johnson, Kevin C; Stan, Radu V; Sanglikar, Aarti; Ahmed, Yashi; Dmitrovsky, Ethan; Freemantle, Sarah J

    2013-01-01

    New pharmacologic targets are urgently needed to treat or prevent lung cancer, the most common cause of cancer death for men and women. This study identified one such target. This is the canonical Wnt signaling pathway, which is deregulated in cancers, including those lacking adenomatous polyposis coli or β-catenin mutations. Two poly-ADP-ribose polymerase (PARP) enzymes regulate canonical Wnt activity: tankyrase (TNKS) 1 and TNKS2. These enzymes poly-ADP-ribosylate (PARsylate) and destabilize axin, a key component of the β-catenin phosphorylation complex. This study used comprehensive gene profiles to uncover deregulation of the Wnt pathway in murine transgenic and human lung cancers, relative to normal lung. Antineoplastic consequences of genetic and pharmacologic targeting of TNKS in murine and human lung cancer cell lines were explored, and validated in vivo in mice by implantation of murine transgenic lung cancer cells engineered with reduced TNKS expression relative to controls. Microarray analyses comparing Wnt pathway members in malignant versus normal tissues of a murine transgenic cyclin E lung cancer model revealed deregulation of Wnt pathway components, including TNKS1 and TNKS2. Real-time PCR assays independently confirmed these results in paired normal-malignant murine and human lung tissues. Individual treatments of a panel of human and murine lung cancer cell lines with the TNKS inhibitors XAV939 and IWR-1 dose-dependently repressed cell growth and increased cellular axin 1 and tankyrase levels. These inhibitors also repressed expression of a Wnt-responsive luciferase construct, implicating the Wnt pathway in conferring these antineoplastic effects. Individual or combined knockdown of TNKS1 and TNKS2 with siRNAs or shRNAs reduced lung cancer cell growth, stabilized axin, and repressed tumor formation in murine xenograft and syngeneic lung cancer models. Findings reported here uncovered deregulation of specific components of the Wnt pathway in both

  3. Glucose-Neopentyl Glycol (GNG) Amphiphiles for Membrane Protein Solubilization, Stabilization and Crystallization

    OpenAIRE

    Chae, Pil Seok; Rana, Rohini R.; Gotfryd, Kamil; Rasmussen, Søren G. F.; Kruse, Andrew C.; Cho, Kyung Ho; Capaldi, Stefano; Carlsson, Emil; Kobilka, Brian; Loland, Claus J.; Gether, Ulrik; Banerjee, Surajit; Byrne, Bernadette; Lee, John K.; Gellman, Samuel H.

    2013-01-01

    The development of a new class of surfactants for membrane protein manipulation, “GNG amphiphiles”, is reported. These amphiphiles display promising behavior for membrane proteins, as demonstrated recently by the high resolution structure of a sodium-pumping pyrophosphatase reported by Kellosalo et al.

  4. Lipid bilayer membranes: Missing link in the comprehension of synovial lubrication?

    Science.gov (United States)

    Packard, Ross; Cowley, Leonie; Dubief, Yves

    2010-03-01

    The human body hosts an extremely efficient tribological system in its synovial joints that operate under very low friction and virtually no wear. It has long been assumed that the higher molecular weight molecules present in the synovial fluid (hyaluronic acid, lubricin) are solely responsible for the mechanical properties of joint. Smaller components, unsaturated phospholipids, have a virtually an undefined role, most probably because of the cancellation of their amphiphilic properties ex vivo caused by oxidation. Using experimental observations of multilamellar arrangements in synovial joints, we formulate the assumption that self-assembling structures provide the anisotropy necessary to synovial fluid to resist drainage under normal compression. Our molecular dynamics simulations demonstrate the tremendous mechanical properties of lipid bilayers and also highlight their weakening consistent with modifications resulting from injuries or joint prosthesis.

  5. Two sides of the coin. Part 1. Lipid and surfactant self-assembly revisited.

    Science.gov (United States)

    Ninham, Barry W; Larsson, Kåre; Lo Nostro, Pierandrea

    2017-04-01

    Hofmeister, specific ion effects, hydration and van der Waals forces at and between interfaces are factors that determine curvature and microstructure in self assembled aggregates of surfactants and lipids; and in microemulsions. Lipid and surfactant head group interactions and between aggregates vary enormously and are highly specific. They act on the hydrophilic side of a bilayer, micelle or other self assembled aggregate. It is only over the last three decades that the origin of Hofmeister effects has become generally understood. Knowledge of their systematics now provides much flexibility in designing nanostructured fluids. The other side of the coin involves equally specific forces. These (opposing) forces work on the hydrophobic side of amphiphilic interfaces. They are due to the interaction of hydrocarbons and other "oils" with hydrophobic tails of surfactants and lipids. The specificity of oleophilic solutes in microemulsions and lipid membranes provides a counterpoint to Hofmeister effects and hydration. Together with global packing constraints these effects determine microstructure. Another factor that has hardly been recognised is the role of dissolved gas. This introduces further, qualitative changes in forces that prescribe microstructure. The systematics of these effects and their interplay are elucidated. Awareness of these competing factors facilitates formulation of self assembled nanostructured fluids. New and predictable geometries that emerge naturally provide insights into a variety of biological phenomena like anaesthetic and pheromone action and transmission of the nervous impulse (see Part 2). Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Glucose-Neopentyl Glycol (GNG) Amphiphiles for Membrane Protein Solubilization, Stabilization and Crystallization

    Science.gov (United States)

    Rana, Rohini R.; Gotfryd, Kamil; Rasmussen, Søren G. F.; Kruse, Andrew C.; Cho, Kyung Ho; Capaldi, Stefano; Carlsson, Emil; Kobilka, Brian; Loland, Claus J.; Gether, Ulrik; Banerjee, Surajit

    2012-01-01

    The development of a new class of surfactants for membrane protein manipulation, “GNG amphiphiles”, is reported. These amphiphiles display promising behavior for membrane proteins, as demonstrated recently by the high resolution structure of a sodium-pumping pyrophosphatase reported by Kellosalo et al. PMID:23165475

  7. Theory of the Flower Micelle Formation of Amphiphilic Random and Periodic Copolymers in Solution

    Directory of Open Access Journals (Sweden)

    Takahiro Sato

    2018-01-01

    Full Text Available The mixing Gibbs energy Δgm for the flower-micelle phase of amphiphilic random and periodic (including alternating copolymers was formulated on the basis of the lattice model. The formulated Δgm predicts (1 the inverse proportionality of the aggregation number to the degree of polymerization of the copolymer, (2 the increase of the critical micelle concentration with decreasing the hydrophobe content, and (3 the crossover from the micellization to the liquid–liquid phase separation as the hydrophobe content increases. The transition from the uni-core flower micelle to the multi-core flower necklace as the degree of polymerization increases was also implicitly indicated by the theory. These theoretical results were compared with experimental results for amphiphilic random and alternating copolymers reported so far.

  8. Investigation on the ion pair amphiphiles and their in vitro release of amantadine drug based on PLGA–PEG–PLGA gel

    International Nuclear Information System (INIS)

    Yang, Xiaoxia; Ji, Xiaoqing; Shi, Chunhuan; Liu, Jing; Wang, Haiyang; Luan, Yuxia

    2014-01-01

    The amantadine drug and oleic acid surfactant are used to form amantadine-based ion pair amphiphiles based on proton transfer reaction between the drug and the surfactant molecules. The ion pair amphiphiles are characterized by 1 H-nuclear magnetic resonance, Fourier transform infrared spectroscopy, and X-ray diffraction. Self-assembly properties of amantadine-based ion pair amphiphiles are studied by surface tension determination, transmission electron microscopy, zeta potential, and dynamic light scattering. The aggregation behavior studies indicate that the as-prepared ion pair amphiphiles can self-assemble into vesicles with the size of 200–300 nm in aqueous solution. The drug release results show that the amantadine release rate could be well controlled by incorporating the amantadine-based ion pair vesicles in poly (lactic-co-glycolic acid)-poly (ethylene glycol)-poly (lactic-co-glycolic acid) (PLGA–PEG–PLGA) copolymer hydrogel. The drug release from the AT–OA vesicle-loaded PLGA–PEG–PLGA hydrogel is significantly inhibited in comparison with the AT-loaded PLGA–PEG–PLGA hydrogel. The present work thus demonstrates that the vesicle-loaded hydrogel is a good candidate for the drug delivery system with long-term controlled drug release behavior

  9. Role of nano-range amphiphilic polymers in seed quality enhancement of soybean and imidacloprid retention capacity on seed coatings.

    Science.gov (United States)

    Adak, Totan; Kumar, Jitendra; Shakil, Najam A; Pandey, Sushil

    2016-10-01

    Nano-size and wide-range solubility of amphiphilic polymers (having both hydrophilic and hydrophobic blocks) can improve uniformity in seed coatings. An investigation was carried out to assess the positive effect of amphiphilic polymers over hydrophilic or hydrophobic polymers as seed coating agents and pesticide carriers. Amphiphilic polymers with 127.5-354 nm micelle size were synthesized in the laboratory using polyethylene glycols and aliphatic di-acids. After 6 months of storage, germination of uncoated soybean seeds decreased drastically from 97.80 to 81.55%, while polymer-coated seeds showed 89.44-95.92% germination. Similarly, vigour index-1 was reduced from 3841.10 to 2813.06 for control seeds but ranged from 3375.59 to 3844.60 for polymer-coated seeds after 6 months. The developed imidacloprid formulations retained more pesticide on soybean seed coatings than did a commercial formulation (Gaucho(®) 600 FS). The time taken for 50% release of imidacloprid from seed coatings in water was 7.12-9.11 h for the developed formulations and 0.41 h for the commercial formulation. Nano-range amphiphilic polymers can be used to protect soybean seeds from ageing. Formulations as seed treatments may produce improved and sustained efficacy with minimum environmental contamination. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  10. Dental anomalies in children submitted to antineoplastic therapy.

    Science.gov (United States)

    Carrillo, Camila Merida; Corrêa, Fernanda Nahás Pires; Lopes, Nilza Nelly Fontana; Fava, Marcelo; Odone Filho, Vicente

    2014-06-01

    Cancer is the third most frequent cause of death in children in Brazil. Early diagnosis and medical advances have significantly improved treatment outcomes, which has resulted in higher survival rates and the management of late side effects has become increasingly important in caring for these patients. Dental abnormalities are commonly observed as late effects of antineoplastic therapy in the oral cavity. The incidence and severity of the dental abnormalities depend on the child's age at diagnosis and the type of chemotherapeutic agent used, as well as the irradiation dose and area. The treatment duration and aggressivity should also be considered. Disturbances in dental development are characterized by changes in shape, number and root development. Enamel anomalies, such as discoloration, opacities and hypoplasia are also observed in these patients. When severe, these abnormalities can cause functional and esthetic sequelae that have an impact on the children's and adolescents' quality of life. General dentists and pediatric dentists should understand these dental abnormalities and how to identify them aiming for early diagnosis and appropriate treatment.

  11. Dental anomalies in children submitted to antineoplastic therapy

    Directory of Open Access Journals (Sweden)

    Camila Merida Carrillo

    2014-06-01

    Full Text Available Cancer is the third most frequent cause of death in children in Brazil. Early diagnosis and medical advances have significantly improved treatment outcomes, which has resulted in higher survival rates and the management of late side effects has become increasingly important in caring for these patients. Dental abnormalities are commonly observed as late effects of antineoplastic therapy in the oral cavity. The incidence and severity of the dental abnormalities depend on the child's age at diagnosis and the type of chemotherapeutic agent used, as well as the irradiation dose and area. The treatment duration and aggressivity should also be considered. Disturbances in dental development are characterized by changes in shape, number and root development. Enamel anomalies, such as discoloration, opacities and hypoplasia are also observed in these patients. When severe, these abnormalities can cause functional and esthetic sequelae that have an impact on the children's and adolescents' quality of life. General dentists and pediatric dentists should understand these dental abnormalities and how to identify them aiming for early diagnosis and appropriate treatment.

  12. Accelerator mass spectrometry analysis of 14C-oxaliplatin concentrations in biological samples and 14C contents in biological samples and antineoplastic agents

    Science.gov (United States)

    Toyoguchi, Teiko; Kobayashi, Takeshi; Konno, Noboru; Shiraishi, Tadashi; Kato, Kazuhiro; Tokanai, Fuyuki

    2015-10-01

    Accelerator mass spectrometry (AMS) is expected to play an important role in microdose trials. In this study, we measured the 14C concentration in 14C-oxaliplatin-spiked serum, urine and supernatant of fecal homogenate samples in our Yamagata University (YU) - AMS system. The calibration curves of 14C concentration in serum, urine and supernatant of fecal homogenate were linear (the correlation coefficients were ⩾0.9893), and the precision and accuracy was within the acceptance criteria. To examine a 14C content of water in three vacuum blood collection tubes and a syringe were measured. 14C was not detected from water in these devices. The mean 14C content in urine samples of 6 healthy Japanese volunteers was 0.144 dpm/mL, and the intra-day fluctuation of 14C content in urine from a volunteer was little. The antineoplastic agents are administered to the patients in combination. Then, 14C contents of the antineoplastic agents were quantitated. 14C contents were different among 10 antineoplastic agents; 14C contents of paclitaxel injection and docetaxel hydrate injection were higher than those of the other injections. These results indicate that our quantitation method using YU-AMS system is suited for microdosing studies and that measurement of baseline and co-administered drugs might be necessary for the studies in low concentrations.

  13. Aminoglycoside-derived amphiphilic nanoparticles for molecular delivery.

    Science.gov (United States)

    Miryala, Bhavani; Godeshala, Sudhakar; Grandhi, Taraka Sai Pavan; Christensen, Matthew D; Tian, Yanqing; Rege, Kaushal

    2016-10-01

    The development of effective drug carriers can lead to improved outcomes in a variety of disease conditions. Aminoglycosides have been used as antibacterial therapeutics, and are attractive as monomers for the development of polymeric materials in various applications. Here, we describe the development of novel aminoglycoside-derived amphiphilic nanoparticles for drug delivery, with an eye towards ablation of cancer cells. The aminoglycoside paromomycin was first cross-linked with resorcinol diglycidyl ether leading to the formation of a poly (amino ether), PAE. PAE molecules were further derivatized with methoxy-terminated poly(ethylene glycol) or mPEG resulting in the formation of mPEG-PAE polymer, which self-assembled to form nanoparticles. Formation of the mPEG-PAE amphiphile was characterized using (1)H NMR, (13)C NMR, gel permeation chromatography (GPC) and FTIR spectroscopy. Self-assembly of the polymer into nanoparticles was characterized using dynamic light scattering, zeta potential analyses, atomic force microscopy (AFM) and the pyrene fluorescence assay. mPEG-PAE nanoparticles were able to carry significant amounts of doxorubicin (DOX), presumably by means of hydrophobic interactions between the drug and the core. Cell-based studies indicated that mPEG-PAE nanoparticles, loaded with doxorubicin, were able to induce significant loss in viabilities of PC3 human prostate cancer, MDA-MB-231 human breast cancer, and MB49 murine bladder cancer cells; empty nanoparticles resulted in negligible losses of cell viability under the conditions investigated. Taken together, our results indicate that the mPEG-PAE nanoparticle platform is attractive for drug delivery in different applications, including cancer. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Preliminary screening of some traditional Zulu medicinal plants for antineoplastic activities versus the HepG2 cell line.

    Science.gov (United States)

    Opoku, A R; Geheeb-Keller, M; Lin, J; Terblanche, S E; Hutchings, A; Chuturgoon, A; Pillay, D

    2000-11-01

    Aqueous and methanol extracts of nine traditional Zulu medicinal plants, Cissus quandrangularis L., Cyphostemma flaviflorum (Sprague) Descoings, Cyphostemma lanigerum (Harv.) Descoings ex Wild & Drum, Cyphostemma natalitium (Szyszyl.) J. v. d. Merwe, Cyphostemma sp., Rhoicissus digitata (L. F.) Gilg & Brandt, Rhoicissus rhomboidea (E. Mey. Ex harv.) Planch, Rhoicissus tomentosa (Lam.) Wild & Drum, R. tridentata (L. F.) Wild & Drum and Rhoicissus tridentata (L. F.) Wild & Drum subsp. cuneifolia (Eckl. & Zeyh.) N. R. Urton, all belonging to the Vitaceae family, were evaluated to determine their therapeutic potentials as antineoplastic agents. The antiproliferative activity in vitro against HepG2 cells was determined. Twenty-two of the twenty-seven crude plant extracts showed activities ranging from 25% to 97% inhibition of proliferation when compared with the control which showed no inhibitory activity. Higher degrees of growth inhibition were found in aqueous root extracts in comparison with the methanol extracts of the same plant parts. The results show potential antineoplastic activity, indicating some scientific validation for traditional usage. Copyright 2000 John Wiley & Sons, Ltd.

  15. Absorption and folding of melittin onto lipid bilayer membranes via unbiased atomic detail microsecond molecular dynamics simulation.

    Science.gov (United States)

    Chen, Charles H; Wiedman, Gregory; Khan, Ayesha; Ulmschneider, Martin B

    2014-09-01

    Unbiased molecular simulation is a powerful tool to study the atomic details driving functional structural changes or folding pathways of highly fluid systems, which present great challenges experimentally. Here we apply unbiased long-timescale molecular dynamics simulation to study the ab initio folding and partitioning of melittin, a template amphiphilic membrane active peptide. The simulations reveal that the peptide binds strongly to the lipid bilayer in an unstructured configuration. Interfacial folding results in a localized bilayer deformation. Akin to purely hydrophobic transmembrane segments the surface bound native helical conformer is highly resistant against thermal denaturation. Circular dichroism spectroscopy experiments confirm the strong binding and thermostability of the peptide. The study highlights the utility of molecular dynamics simulations for studying transient mechanisms in fluid lipid bilayer systems. This article is part of a Special Issue entitled: Interfacially Active Peptides and Proteins. Guest Editors: William C. Wimley and Kalina Hristova. Copyright © 2014. Published by Elsevier B.V.

  16. Synthesis and evaluation of amphiphilic peptides as nanostructures and drug delivery tools

    Science.gov (United States)

    Sayeh, Naser Ali

    Intracellular delivery of cell-impermeable compounds in a variety cells using delivery systems have been extensively studied in recent years. Obtaining desirable cellular uptake levels often requires the administration of high quantities of drugs to achieve the expected intracellular biological effect. Thus, improving the translocation process across the plasma membrane will significantly reduce the quantity of required administered drug and consequently minimize the side effects in most of the cases. Efficient delivery of these molecules to the cells and tissues is a difficult challenge. Compounds with low cellular permeability are commonly considered to be of limited therapeutic value. Over the past few decades, several biomedical carriers, such as polymers, nanospheres, nanocapsules, liposomes, micelles, peptides and dendrimers have been widely used to deliver therapeutic and diagnostic agents to the cells. Biomaterials generated from nano-scale compounds have shown some promising data for delivery of many compounds in a number of diseases, such as viral infections, cancer, and genetic disorders. Although much progress has been achieved in this field, many challenges still remain, such as toxicity and limited stability. Liposomes suffer from poor stability in the bloodstream and leakage during storage. They tend to aggregate and fuse with or leak entrapped drugs, especially highly hydrophilic small molecules. For solid lipid nanoparticles (SLNs), drug expulsion after polymorphic transition during storage, inadequate loading capacity, and relatively high water content of the dispersions have been observed. Poly(lactic-coglycolic acid (PLGA) degrades in the body producing its original monomers of lactic acid and glycolic acid, which are the by-products of various metabolic pathways. However, this acidic microenvironment that occurs during degradation could negatively affect the stability of the loaded compound. Dendrimers can carry drugs as complexes or as

  17. From superamphiphobic to amphiphilic polymeric surfaces with ordered hierarchical roughness fabricated with colloidal lithography and plasma nanotexturing.

    Science.gov (United States)

    Ellinas, K; Tserepi, A; Gogolides, E

    2011-04-05

    Ordered, hierarchical (triple-scale), superhydrophobic, oleophobic, superoleophobic, and amphiphilic surfaces on poly(methyl methacrylate) PMMA polymer substrates are fabricated using polystyrene (PS) microparticle colloidal lithography, followed by oxygen plasma etching-nanotexturing (for amphiphilic surfaces) and optional subsequent fluorocarbon plasma deposition (for amphiphobic surfaces). The PS colloidal microparticles were assembled by spin-coating. After etching/nanotexturing, the PMMA plates are amphiphilic and exhibit hierarchical (triple-scale) roughness with microscale ordered columns, and dual-scale (hundred nano/ten nano meter) nanoscale texture on the particles (top of the column) and on the etched PMMA surface. The spacing, diameter, height, and reentrant profile of the microcolumns are controlled with the etching process. Following the design requirements for superamphiphobic surfaces, we demonstrate enhancement of both hydrophobicity and oleophobicity as a result of hierarchical (triple-scale) and re-entrant topography. After fluorocarbon film deposition, we demonstrate superhydrophobic surfaces (contact angle for water 168°, compared to 110° for a flat surface), as well as superoleophobic surfaces (153° for diiodomethane, compared to 80° for a flat surface).

  18. A Review of the Role of Amphiphiles in Biomass to Ethanol Conversion

    Directory of Open Access Journals (Sweden)

    William Gibbons

    2013-04-01

    Full Text Available One of the concerns for economical production of ethanol from biomass is the large volume and high cost of the cellulolytic enzymes used to convert biomass into fermentable sugars. The presence of acetyl groups in hemicellulose and lignin in plant cell walls reduces accessibility of biomass to the enzymes and makes conversion a slow process. In addition to low enzyme accessibility, a rapid deactivation of cellulases during biomass hydrolysis can be another factor contributing to the low sugar recovery. As of now, the economical reduction in lignin content of the biomass is considered a bottleneck, and raises issues for several reasons. The presence of lignin in biomass reduces the swelling of cellulose fibrils and accessibility of enzyme to carbohydrate polymers. It also causes an irreversible adsorption of the cellulolytic enzymes that prevents effective enzyme activity and recycling. Amphiphiles, such as surfactants and proteins have been found to improve enzyme activity by several mechanisms of action that are not yet fully understood. Reduction in irreversible adsorption of enzyme to non-specific sites, reduction in viscosity of liquid and surface tension and consequently reduced contact of enzyme with air-liquid interface, and modifications in biomass chemical structure are some of the benefits derived from surface active molecules. Application of some of these amphiphiles could potentially reduce the capital and operating costs of bioethanol production by reducing fermentation time and the amount of enzyme used for saccharification of biomass. In this review article, the benefit of applying amphiphiles at various stages of ethanol production (i.e., pretreatment, hydrolysis and hydrolysis-fermentation is reviewed and the proposed mechanisms of actions are described.

  19. Tetrazole amphiphile inducing growth of conducting polymers hierarchical nanostructures and their electromagnetic absorption properties

    Science.gov (United States)

    Xie, Aming; Sun, Mengxiao; Zhang, Kun; Xia, Yilu; Wu, Fan

    2018-05-01

    Conducting polymers (CPs) at nano scales endow materials with special optical, electrical, and magnetic properties. The crucial factor to construct and regulate the micro-structures of CPs is the inducing reagent, particular in its chemical structure, such active sites, self-assembling properties. In this paper, we design and synthesize an amphiphile bearing tetrazole moiety on its skeleton, and use this amphiphile as an inducing reagent to prepare and regulate the micro-structures of a series of CPs including polypyrrole, polyaniline, poly(3,4-ethylenedioxythiophene) and poly(p-phenylenediamine). Because of the unique electric properties of CPs and size effect, we next explored the electromagnetic absorption performances of these CPs nanostructures. A synergetic combination of electric loss and magnetic loss is used to explain the absorption mechanism of these CPs nano-structures.

  20. Synthesis of an amphiphilic dendrimer-like block copolymer and its application on drug delivery

    KAUST Repository

    Wang, Shuaipeng

    2014-10-27

    Dendrimer-like amphiphilic copolymer is a kind of three-dimensional spherical structure polymer. An amphiphilic dendrimer-like diblock copolymer, PEEGE-G2-b-PEO(OH)12, constituted of a hydrophobic poly(ethoxyethyl glycidol ether) inner core and a hydrophilic poly(ethylene oxide) outer layer, has been successfully synthesized by the living anionic ring-opening polymerization method. The intermediates and targeted products were characterized with 1H NMR spectroscopy and gel permeation chromatography. The application on drug delivery of dendrimer-like diblock copolymer PEEGE-G2-b-PEO(OH)12 using DOX as a model drug was also studied. The drug loading content and encapsulation efficiency were found at 13.07% and 45.75%, respectively. In vitro release experiment results indicated that the drug-loaded micelles exhibited a sustained release behavior under acidic media.

  1. New amphiphilic glycopolypeptide conjugate capable of self-assembly in water into reduction-sensitive micelles for triggered drug release

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Hui-Kang [DSAPM Lab and PCFM Lab, Department of Polymer and Materials Science, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275 (China); Zhang, Li-Ming, E-mail: ceszhlm@mail.sysu.edu.cn [DSAPM Lab and PCFM Lab, Department of Polymer and Materials Science, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275 (China); Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Science, Sun Yat-sen University, Guangzhou 510006 (China)

    2014-08-01

    For the development of biomimetic carriers for stimuli-sensitive delivery of anticancer drugs, a novel amphiphilic glycopolypeptide conjugate containing the disulfide bond was prepared for the first time by the ring-opening polymerization of benzyl glutamate N-carboxy anhydride in the presence of (propargyl carbamate)ethyl dithio ethylamine and then click conjugation with α-azido dextran. Its structure was characterized by Fourier-transform infrared spectroscopy and nuclear magnetic resonance analyses. Owing to its amphiphilic nature, such a conjugate could self assemble into nanosize micelles in aqueous medium, as confirmed by fluorometry, transmission electron microscopy and dynamic light scattering. For the resultant micelles, it was found to encapsulate poorly water-soluble anticancer drug (methotrexate, MTX) with the loading efficiency of 45.2%. By the in vitro drug release tests, the release rate of encapsulated MTX was observed to be accelerated significantly in the presence of 10 mM 1,4-dithio-DL-threitol (DTT), analogous to the intracellular redox potential. - Graphical abstract: New amphiphilic glycopolypeptide conjugate containing the disulfide bond could self-assemble in aqueous solution into reduction-sensitive micelles for triggered release of an anticancer drug (methotrexate, MTX) in the presence of 10 mM 1,4-dithio-DL-threitol (DTT). - Highlights: • Amphiphilic glycopolypeptide conjugate containing disulfide bond was prepared. • Such a conjugate self assembled in aqueous solution into nanosize micelles. • The resultant micelles could encapsulate effectively methotrexate drug. • The drug-loaded micelles showed a reduction-sensitive drug release behavior.

  2. New amphiphilic glycopolypeptide conjugate capable of self-assembly in water into reduction-sensitive micelles for triggered drug release

    International Nuclear Information System (INIS)

    Yang, Hui-Kang; Zhang, Li-Ming

    2014-01-01

    For the development of biomimetic carriers for stimuli-sensitive delivery of anticancer drugs, a novel amphiphilic glycopolypeptide conjugate containing the disulfide bond was prepared for the first time by the ring-opening polymerization of benzyl glutamate N-carboxy anhydride in the presence of (propargyl carbamate)ethyl dithio ethylamine and then click conjugation with α-azido dextran. Its structure was characterized by Fourier-transform infrared spectroscopy and nuclear magnetic resonance analyses. Owing to its amphiphilic nature, such a conjugate could self assemble into nanosize micelles in aqueous medium, as confirmed by fluorometry, transmission electron microscopy and dynamic light scattering. For the resultant micelles, it was found to encapsulate poorly water-soluble anticancer drug (methotrexate, MTX) with the loading efficiency of 45.2%. By the in vitro drug release tests, the release rate of encapsulated MTX was observed to be accelerated significantly in the presence of 10 mM 1,4-dithio-DL-threitol (DTT), analogous to the intracellular redox potential. - Graphical abstract: New amphiphilic glycopolypeptide conjugate containing the disulfide bond could self-assemble in aqueous solution into reduction-sensitive micelles for triggered release of an anticancer drug (methotrexate, MTX) in the presence of 10 mM 1,4-dithio-DL-threitol (DTT). - Highlights: • Amphiphilic glycopolypeptide conjugate containing disulfide bond was prepared. • Such a conjugate self assembled in aqueous solution into nanosize micelles. • The resultant micelles could encapsulate effectively methotrexate drug. • The drug-loaded micelles showed a reduction-sensitive drug release behavior

  3. Methotrexate-Loaded Four-Arm Star Amphiphilic Block Copolymer Elicits CD8+ T Cell Response against a Highly Aggressive and Metastatic Experimental Lymphoma.

    Science.gov (United States)

    Hira, Sumit Kumar; Ramesh, Kalyan; Gupta, Uttam; Mitra, Kheyanath; Misra, Nira; Ray, Biswajit; Manna, Partha Pratim

    2015-09-16

    We have synthesized a well-defined four-arm star amphiphilic block copolymer [poly(DLLA)-b-poly(NVP)]4 [star-(PDLLA-b-PNVP)4] that consists of D,L-lactide (DLLA) and N-vinylpyrrolidone (NVP) via the combination of ring-opening polymerization (ROP) and xanthate-mediated reversible addition-fragmentation chain transfer (RAFT) polymerization. Synthesis of the polymer was verified by 1H NMR spectroscopy and gel permeation chromatography (GPC). The amphiphilic four-arm star block copolymer forms spherical micelles in water as demonstrated by transmission electron microscopy (TEM) and 1H NMR spectroscopy. Pyrene acts as a probe to ascertain the critical micellar concentration (cmc) by using fluorescence spectroscopy. Methotrexate (MTX)-loaded polymeric micelles of star-(PDLLA15-b-PNVP10)4 amphiphilic block copolymer were prepared and characterized by fluorescence and TEM studies. Star-(PDLLA15-b-PNVP10)4 copolymer was found to be significantly effective with respect to inhibition of proliferation and lysis of human and murine lymphoma cells. The amphiphilic block copolymer causes cell death in parental and MTX-resistant Dalton lymphoma (DL) and Raji cells. The formulation does not cause hemolysis in red blood cells and is tolerant to lymphocytes compared to free MTX. Therapy with MTX-loaded star-(PDLLA15-b-PNVP10)4 amphiphilic block copolymer micelles prolongs the life span of animals with neoplasia by reducing the tumor load, preventing metastasis and augmenting CD8+ T cell-mediated adaptive immune responses.

  4. Transfection of small numbers of human endothelial cells by electroporation and synthetic amphiphiles

    NARCIS (Netherlands)

    van Leeuwen, E B; van der Veen, A Y; Hoekstra, D; Engberts, J B; Halie, M R; van der Meer, J; Ruiters, M H

    OBJECTIVES: This study compared the efficiency of electroporation and synthetic amphiphiles. (SAINT-2pp/DOPE) in transfecting small numbers of human endothelial cells. METHODS AND RESULTS: Optimal transfection conditions were tested and appeared to be 400 V and 960 microF for electroporation and a

  5. Immunochemically identical hydrophilic and amphiphilic forms of the bovine adrenomedullary dopamine beta-hydroxylase

    DEFF Research Database (Denmark)

    Bjerrum, Ole Jannik; Helle, K B; Bock, Elisabeth Marianne

    1979-01-01

    . The dopamine beta-hydroxylases of the buffer and membrane fractions were antigenically identical, but differed in their amphiphilicity, as demonstrated by the change in precipitation patterns on removal of Triton X-100 from the gel, on charge-shift crossed immunoelectrophoresis and on crossed hydrophobic...

  6. Hypersensitivity and desensitization to antineoplastic agents: outcomes of 189 procedures with a new short protocol and novel diagnostic tools assessment.

    Science.gov (United States)

    Madrigal-Burgaleta, R; Berges-Gimeno, M P; Angel-Pereira, D; Ferreiro-Monteagudo, R; Guillen-Ponce, C; Pueyo, C; Gomez de Salazar, E; Alvarez-Cuesta, E

    2013-07-01

    Desensitization to antineoplastic agents is becoming a standard of care. Efforts to establish and improve these techniques are being made at many institutions. Our aims are to evaluate a new rapid desensitization protocol designed to be shorter (approximately 4 h) and safer (reducing hazardous drugs exposure risks) and to assess the oxaliplatin-specific immunoglobulin E (IgE) as a novel diagnostic tool. Prospective, observational, longitudinal study with patients who, for a 1-year period, suffered reactions to antineoplastic agents and were referred to the Desensitization Program at Ramon y Cajal University Hospital (RCUH). Patients were included or excluded as desensitization candidates after anamnesis, skin testing, risk assessment, and graded challenge. Specific IgE was determined in oxaliplatin-reactive patients. Candidate patients were desensitized using the new RCUH rapid desensitization protocol. Of 189 intravenous rapid desensitizations, 188 were successfully accomplished in the 23 patients who met inclusion criteria for desensitization (of 58 referred patients). No breakthrough reactions occurred in 94% of desensitizations, and most breakthrough reactions were mild. In 10 oxaliplatin-reactive patients, 38 desensitizations were successfully accomplished. Sensitivity for oxaliplatin-specific IgE was 38% (0.35UI/l cutoff point) and 54% (0.10UI/l cutoff point); specificity was 100% for both cutoff points. In the hands of a Desensitization Program, managed by drug desensitization experts, this new protocol has proven an effective therapeutic tool for hypersensitivity to several antineoplastic agents (oxaliplatin, carboplatin, paclitaxel, docetaxel, cyclophosphamide, and rituximab); moreover, it improves safety handling of hazardous drugs. We report the first large series of oxaliplatin desensitizations. Oxaliplatin-specific IgE determination could be helpful. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Multiple cationic amphiphiles induce a Niemann-Pick C phenotype and inhibit Ebola virus entry and infection.

    Directory of Open Access Journals (Sweden)

    Charles J Shoemaker

    Full Text Available Ebola virus (EBOV is an enveloped RNA virus that causes hemorrhagic fever in humans and non-human primates. Infection requires internalization from the cell surface and trafficking to a late endocytic compartment, where viral fusion occurs, providing a conduit for the viral genome to enter the cytoplasm and initiate replication. In a concurrent study, we identified clomiphene as a potent inhibitor of EBOV entry. Here, we screened eleven inhibitors that target the same biosynthetic pathway as clomiphene. From this screen we identified six compounds, including U18666A, that block EBOV infection (IC(50 1.6 to 8.0 µM at a late stage of entry. Intriguingly, all six are cationic amphiphiles that share additional chemical features. U18666A induces phenotypes, including cholesterol accumulation in endosomes, associated with defects in Niemann-Pick C1 protein (NPC1, a late endosomal and lysosomal protein required for EBOV entry. We tested and found that all six EBOV entry inhibitors from our screen induced cholesterol accumulation. We further showed that higher concentrations of cationic amphiphiles are required to inhibit EBOV entry into cells that overexpress NPC1 than parental cells, supporting the contention that they inhibit EBOV entry in an NPC1-dependent manner. A previously reported inhibitor, compound 3.47, inhibits EBOV entry by blocking binding of the EBOV glycoprotein to NPC1. None of the cationic amphiphiles tested had this effect. Hence, multiple cationic amphiphiles (including several FDA approved agents inhibit EBOV entry in an NPC1-dependent fashion, but by a mechanism distinct from that of compound 3.47. Our findings suggest that there are minimally two ways of perturbing NPC1-dependent pathways that can block EBOV entry, increasing the attractiveness of NPC1 as an anti-filoviral therapeutic target.

  8. Triton X-100 inhibits agonist-induced currents and suppresses benzodiazepine modulation of GABA(A) receptors in Xenopus oocytes

    DEFF Research Database (Denmark)

    Søgaard, Rikke; Ebert, Bjarke; Klaerke, Dan

    2009-01-01

    Changes in lipid bilayer elastic properties have been proposed to underlie the modulation of voltage-gated Na(+) and L-type Ca(2+) channels and GABA(A) receptors by amphiphiles. The amphiphile Triton X-100 increases the elasticity of lipid bilayers at micromolar concentrations, assessed from its...... by flunitrazepam at alpha(1)beta(3)gamma(2S) receptors. All effects were independent of the presence of a gamma(2S) subunit in the GABA(A) receptor complex. The present study suggests that Triton X-100 may stabilize open and desensitized states of the GABA(A) receptor through changes in lipid bilayer elasticity....

  9. Amphiphilic block copolymers as efficiency boosters in microemulsions a SANS investigation of the role of polymers

    CERN Document Server

    Endo, H; Mihailescu, M; Monkenbusch, M; Gompper, G; Richter, D; Jakobs, B; Sottmann, T; Strey, R

    2002-01-01

    The effect of amphiphilic block copolymers on ternary microemulsions (water, oil and non-ionic surfactant) is investigated. Small amounts of PEP-PEO block copolymer lead to a dramatic expansion of the one-phase region where water and oil can be solubilized by the mediation of surfactant molecules. Small-angle neutron-scattering experiments employing a high-precision two-dimensional contrast-variation technique demonstrate that the polymer is distributed uniformly on the surfactant membrane, where it modifies the membrane curvature elasticity. Furthermore, a new approach to determine the bending rigidity of an amphiphilic membrane is proposed, which is precise enough to measure the logarithmic scale dependence of the bending rigidity and its universal prefactor in bicontinuous microemulsions. (orig.)

  10. Self-assembly of block copolymer-based ionic supramolecules based upon multi-tail amphiphiles

    DEFF Research Database (Denmark)

    Asad Ayoubi, M.; Almdal, Kristoffer; Zhu, K.

    2015-01-01

    Utilising simple acid-base titration chemistry, a new family of Linear-b-Amphiphilic Comb (L-b-AC) ionic supramolecules [Soft Matter 2013, 9, 1540-1555] featuring multi-tail side-chains have been synthesized and examined by synchrotron SAXS. To three different parent diblock copolymers of poly...

  11. Novel amphiphilic poly(dimethylsiloxane) based polyurethane networks tethered with carboxybetaine and their combined antibacterial and anti-adhesive property

    Science.gov (United States)

    Jiang, Jingxian; Fu, Yuchen; Zhang, Qinghua; Zhan, Xiaoli; Chen, Fengqiu

    2017-08-01

    The traditional nonfouling materials are powerless against bacterial cells attachment, while the hydrophobic bactericidal surfaces always suffer from nonspecific protein adsorption and dead bacterial cells accumulation. Here, amphiphilic polyurethane (PU) networks modified with poly(dimethylsiloxane) (PDMS) and cationic carboxybetaine diol through simple crosslinking reaction were developed, which had an antibacterial efficiency of 97.7%. Thereafter, the hydrolysis of carboxybetaine ester into zwitterionic groups brought about anti-adhesive properties against bacteria and proteins. The surface chemical composition and wettability performance of the PU network surfaces were investigated by attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS) and contact angle analysis. The surface distribution of PDMS and zwitterionic segments produced an obvious amphiphilic heterogeneous surface, which was demonstrated by atomic force microscopy (AFM). Enzyme-linked immunosorbent assays (ELISA) were used to test the nonspecific protein adsorption behaviors. With the advantages of the transition from excellent bactericidal performance to anti-adhesion and the combination of fouling resistance and fouling release property, the designed PDMS-based amphiphilic PU network shows great application potential in biomedical devices and marine facilities.

  12. Anchoring cationic amphiphiles for nucleotide delivery: significance of DNA release from cationic liposomes for transfection.

    Science.gov (United States)

    Hirashima, Naohide; Minatani, Kazuhiro; Hattori, Yoshifumi; Ohwada, Tomohiko; Nakanishi, Mamoru

    2007-06-01

    We have designed and synthesized lithocholic acid-based cationic amphiphile molecules as components of cationic liposomes for gene transfection (lipofection). To study the relationship between the molecular structures of those amphiphilic molecules, particularly the extended hydrophobic appendant (anchor) at the 3-hydroxyl group, and transfection efficiency, we synthesized several lithocholic and isolithocholic acid derivatives, and examined their transfection efficiency. We also compared the physico-chemical properties of cationic liposomes prepared from these derivatives. We found that isolithocholic acid derivatives exhibit higher transfection efficiency than the corresponding lithocholic acid derivatives. This result indicates that the orientation and extension of hydrophobic regions influence the gene transfection process. Isolithocholic acid derivatives showed a high ability to encapsulate DNA in a compact liposome-DNA complex and to protect it from enzymatic degradation. Isolithocholic acid derivatives also facilitated the release of DNA from the liposome-DNA complex, which is a crucial step for DNA entry into the nucleus. Our results show that the transfection efficiency is directly influenced by the ability of the liposome complex to release DNA, rather than by the DNA-encapsulating ability. Molecular modeling revealed that isolithocholic acid derivatives take relatively extended conformations, while the lithocholic acid derivatives take folded structures. Thus, the efficiency of release of DNA from cationic liposomes in the cytoplasm, which contributes to high transfection efficiency, appears to be dependent upon the molecular shape of the cationic amphiphiles.

  13. Peptide amphiphile nanoparticles enhance the immune response against a CpG-adjuvanted influenza antigen

    NARCIS (Netherlands)

    Zope, H.; Quer, C.B.; Bomans, P.H.H.; Sommerdijk, N.A.J.M.; Kros, A.; Jiskoot, W.

    2014-01-01

    Cationic peptide amphiphile nanoparticles are employed for co-delivery of immune modulator CpG and antigen. This results in better targeting to the antigen presenting cells and eliciting strong Th1 response, which is effective against the intracellular pathogens.

  14. In-vitro cytotoxic activities of poly(2-ethyl-2-oxazoline-based amphiphilic block copolymers prepared by CuAAC click chemistry

    Directory of Open Access Journals (Sweden)

    S. Gulyuz

    2018-02-01

    Full Text Available Synthesis and characterization of well-defined amphiphilic block copolymers containing poly(2-ethyl-2-oxazoline as hydrophilic block and poly(ε-caprolactone or poly(L-lactide as hydrophobic block is achieved by copper-catalyzed azide-alkyne cycloaddition (CuAAC click chemistry. The clickable precursors, α-alkyne-functionalized poly(ε-caprolactone and poly(L-lactide and ω-azido-functionalized poly(2-ethyl-2-oxazoline are simply prepared and joined using copper sulfate/ascorbic acid catalyst system at room temperature. The structures of precursors and amphiphilic block copolymers are characterized by spectroscopic, chromatographic and thermal analyses. The cytotoxic activities of resulting amphiphilic block copolymers and their precursors are investigated in the prostate epithelial and cancer cells under in-vitro conditions. The treatment of the healthy prostate epithelial cell line PNT1A reveals that no significant cytotoxicity, whereas some significant toxic effects on the prostate cancer cell lines are observed.

  15. Ga(III) chelates of amphiphilic DOTA-based ligands: synthetic route and in vitro and in vivo studies

    International Nuclear Information System (INIS)

    Fontes, Andre; Prata, M. Isabel M.; Geraldes, Carlos F.G.C.; Andre, Joao P.

    2011-01-01

    In this work, we report on a synthetic strategy using amphiphilic DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid)-based chelators bearing a variable-sized α-alkyl chain at one of the pendant acetate arms (from 6 to 14 carbon atoms), compatible with their covalent coupling to amine-bearing biomolecules. The amphiphilic behavior of the micelles-forming Ga(III) chelates (critical micellar concentration), their stability in blood serum and their lipophilicity (logP) were investigated. Biodistribution studies with the 67 Ga-labeled chelates were performed in Wistar rats, which showed a predominant liver uptake with almost no traces of the radiochelates in the body after 24 h.

  16. Unconventional, amphiphilic polymers based on chiral polyethylene oxide derivatives I. Synthesis and Characterization.

    NARCIS (Netherlands)

    Janssen, H.M.; Peeters, E.; Zundert, van M.F.; Genderen, van M.H.P.; Meijer, E.W.

    1997-01-01

    The first representatives of a new class of synthetic, amphiphilic polymers based on poly(ethylene oxide) are introduced. These polymers are constituted in a similar way to that for coiled-coil-forming peptides: the polymers possess a regular repeat of apolar (A) residues in a polar (P) sequence of

  17. Novel self-associative and multiphase nanostructured soft carriers based on amphiphilic hyaluronic acid derivatives

    DEFF Research Database (Denmark)

    Eenschooten, Corinne; Vaccaro, Andrea; Delie, Florence

    2012-01-01

    The purpose of the present study was to investigate the physicochemical properties in aqueous media of amphiphilic hyaluronic acid (HA) derivatives obtained by reaction of HA’s hydroxyl groups with octenyl succinic anhydride (OSA). The self-associative properties of the resulting octenyl succinic...

  18. Lipid droplets, perilipins and cytokeratins--unravelled liaisons in epithelium-derived cells.

    Directory of Open Access Journals (Sweden)

    Hans Heid

    Full Text Available Lipid droplets (LDs are spherical accumulations of apolar lipids and other hydrophobic substances and are generally surrounded by a thin cortical layer of specific amphiphilic proteins (APs. These APs segregate the LDs from the mostly polar components of the cytoplasm. We have studied LDs in epithelium-derived cell cultures and in particular characterized proteins from the perilipin (PLIN gene family - in mammals consisting of the proteins Perilipin, Adipophilin, TIP47, S3-12 and MLDP/OXPAT (PLIN 1-5. Using a large number of newly generated and highly specific mono- and polyclonal antibodies specific for individual APs, and using improved LD isolation methods, we have enriched and characterized APs in greater detail and purity. The majority of lipid-AP complexes could be obtained in the top layer fractions of density gradient centrifugation separations of cultured cells, but APs could also be detected in other fractions within such separations. The differently sized LD complexes were analyzed using various biochemical methods and mass spectrometry as well as immunofluorescence and electron- in particular immunoelectron-microscopy. Moreover, by immunoprecipitation, protein-protein binding assays and by immunoelectron microscopy we identified a direct linkage between LD-binding proteins and the intermediate-sized filaments (IF cytokeratins 8 and 18 (also designated as keratins K8 and K18. Specifically, in gradient fractions of higher density supposedly containing small LDs, we received as co-precipitations cytidylyl-, palmitoyl- and cholesterol transferases and other specific enzymes involved in lipid metabolism. So far, common proteomic studies have used LDs from top layer fractions only and did not report on these transferases and other enzymes. In addition to findings of short alternating hydrophobic/hydrophilic segments within the PLIN protein family, we propose and discuss a model for the interaction of LD-coating APs with IF proteins.

  19. Synthesis of amphiphilic macrocyclic molecules from family of aza-porphyrins and study in Langmuir-Blodgett films; Synthese de molecules macrocycliques amphiphiles de la famille des azaporphyrines et etude en films de Langmuir-Blodgett

    Energy Technology Data Exchange (ETDEWEB)

    Palacin, Serge

    1988-03-04

    The cellular automata, also called formal neurons, directly inspired by the knowledge concerning the nervous system, are able to mimic some basic processes of brain, as shape recognition, connecting memory, information sorting... This work aims to build a molecular structure able to fit the working rules of a bidimensional cellular automata. So, amphiphilic molecules belonging to the aza-porphyrin family are synthesized and organized into a planar paving by the Langmuir-Blodgett technique. The regular structure of the outcoming ultra-thin films is studied by linear dichroism and anisotropic electron spin resonance. The physico-chemical behaviour of the amphiphilic molecules is studied and brings about an explanation of the redox phenomena which are observed on the monomolecular film on the water surface. So are we able to outline the future chemical addressing ways of the bidimensional cellular automata. In the end of this dissertation, different ways likely to insure covalent bindings between the active sites and allow the transfer of information within the cellular network are discussed. (author) [French] Les reseaux d'automates, aussi appeles neurones formels, directement inspires par les connaissances nouvelles concernant le fonctionnement du systeme nerveux, sont a l'heure actuelle capables de reproduire certaines operations fondamentales du cerveau, telles que la reconnaissance de forme, la memoire associative, le tri d'information... Le travail a pour but de realiser une structure moleculaire susceptible d'obeir aux regles de fonctionnement d'un automate cellulaire bi-dimensionnel. Dans ce but, des molecules amphiphiles de la famille des azaporphyrines sont synthetisees et organisees en un pavage plan par la methode de Langmuir-Blodgett. La structure reguliere des films ultraminces obtenus est determinee par dichroisme lineaire et resonance paramagnetique electronique anisotrope. Les caracteristiques physico-chimiques des molecules amphiphiles sont etudiees

  20. A new class of amphiphiles: annelids; Une nouvelle classe d'amphiphiles: les annelides

    Energy Technology Data Exchange (ETDEWEB)

    Markovitsi, Dimitra

    1983-12-14

    This research thesis presents annelids, organometallic compounds which may form into organised phases. The author describes the synthesis of an amphipathic ligand of its cobaltic and cupric complexes. The formation of micelles and of thermotropic and lyotropic liquid crystals is highlighted. The copper (II) annelid environment is studied by electronic paramagnetic resonance spectroscopy. The author demonstrates, in micellar phase, the effect of molecular cooperativity on acid-base balance, on metallic ion complexation, on the photo-sensitized electronic transfer, and on the formation of poly-nuclear complexes [French] Les annelides, composes organometalliques susceptibles de former des phases organisees, sont presentes. La synthese d'un ligand amphipathique et de ses complexes cobaltique et cuivrique est decrite. La formation de micelles et de cristaux liquides, thermotropes et lyotropes, a l'aide de ces amphiphiles, est mise en evidence. L'environnement de l'annelide de cuivre (II) est etudie par spectroscopie de resonance paramagnetique electronique. L'effet de la cooperativite moleculaire sur l'equilibre acidobasique, sur la complexation des ions metalliques, sur le transfert electronique photosensibilise et sur la formation des complexes polynucleaires est demontre en phase micellaire. (auteur)

  1. Spatially explicit prioritization of human antibiotics and antineoplastics in Europe.

    Science.gov (United States)

    Oldenkamp, Rik; Huijbregts, Mark A J; Hollander, Anne; Versporten, Ann; Goossens, Herman; Ragas, Ad M J

    2013-01-01

    This paper presents a screening tool for the location-specific prioritization of human pharmaceutical emissions in Europe, based on risk quotients for the aquatic environment and human health. The tool provides direction towards either monitoring activities or additional research. Its application is illustrated for a set of 11 human antibiotics and 7 antineoplastics. Risk quotients for the aquatic environment were highest for levofloxacin, doxycycline and ciprofloxacin, located in Northern Italy (Milan region; particularly levofloxacin) and other densely populated areas in Europe (e.g. London, Krakow and the Ruhr area). Risk quotients for human health not only depend on pharmaceutical and location, but also on behavioral characteristics, such as consumption patterns. Infants in eastern Spain that consume locally produced food and conventionally treated drinking water were predicted to run the highest risks. A limited comparison with measured concentrations in surface water showed that predicted and measured concentrations are approximately within one order of magnitude. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Structure and reactivity in amphiphile-water micelles

    International Nuclear Information System (INIS)

    Chevalier, Yves

    1985-01-01

    Following a review of the general properties of micelles, this report contains two parts: - A structural study of octylphosphate micelles. Important structural changes have been evidenced by mean of small angle neutron scattering as the electrical charge of the interface is varied. The NMR relaxation study of the conformation of the hydrocarbon chains has shown that the micellar core is disordered in contrast with the interface which is rather structured. The diffusion motions in the interface and the segmental motions of the chains are fast. - Studies on the reactivity in micelles have been carried out. A large micellar effect on the complexation of transition ions by amphiphilic ligands is evidenced. The problem of solute localization in micelles is developed with few examples. (author) [fr

  3. Differential thermodynamic signature of carbon nanomaterials using amphiphilic micellar probe

    Science.gov (United States)

    Bhattacharyya, Tamoghna; Dasgupta, Anjan Kr

    2018-04-01

    The thermodynamic signature of single-wall carbon nanotubes (SWCNTs), multi-walled carbon nanotubes (MWCNTs) and reduced graphene oxide (rG-O) using amphiphilic micellar probe has been explored. The study reveals an intricate correlation between nano-surface topology and calorimetric profile of SWCNTs, MWCNTs and rG-O. The critical micelle concentration (CMC) is found to be sensitive to the topological diversity of nanomaterials. The study explores a thermodynamic approach to characterize the nano-surface topology of SWCNTs, MWCNTs and graphene surface.

  4. Ga(III) chelates of amphiphilic DOTA-based ligands: synthetic route and in vitro and in vivo studies

    Energy Technology Data Exchange (ETDEWEB)

    Fontes, Andre [Centro de Quimica, Campus de Gualtar, Universidade do Minho, 4710-057, Braga (Portugal); Prata, M. Isabel M. [IBILI, Faculdade de Medicina, Universidade de Coimbra, 3548, Coimbra (Portugal); Geraldes, Carlos F.G.C. [Departamento de Ciencias da Vida, Faculdade de Ciencias e Tecnologia, Universidade de Coimbra, 3001-401, Coimbra (Portugal); Centro de Neurociencias e Biologia Celular, Universidade de Coimbra, 3001-401, Coimbra (Portugal); Andre, Joao P., E-mail: jandre@quimica.uminho.p [Centro de Quimica, Campus de Gualtar, Universidade do Minho, 4710-057, Braga (Portugal)

    2011-04-15

    In this work, we report on a synthetic strategy using amphiphilic DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid)-based chelators bearing a variable-sized {alpha}-alkyl chain at one of the pendant acetate arms (from 6 to 14 carbon atoms), compatible with their covalent coupling to amine-bearing biomolecules. The amphiphilic behavior of the micelles-forming Ga(III) chelates (critical micellar concentration), their stability in blood serum and their lipophilicity (logP) were investigated. Biodistribution studies with the {sup 67}Ga-labeled chelates were performed in Wistar rats, which showed a predominant liver uptake with almost no traces of the radiochelates in the body after 24 h.

  5. Self-Assembly of Amphiphilic Block Copolypeptoids with C 2 -C 5 Side Chains in Aqueous Solution

    KAUST Repository

    Fetsch, Corinna

    2014-12-22

    © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Nowadays, amphiphilic molecules play an important role in our life. In medical applications, amphiphilic block copolymers have attracted much attention as excipients in drug delivery systems. Here, the polymers are used as emulsifiers, micelles, or polymersomes with a hydrophilic corona block and a hydrophobic core or membrane. The aggregation behavior in aqueous solutions of a series of different amphiphilic block copolypeptoids comprising polysarcosine as a hydrophilic part is here reported. The formation of aggregates is investigated with 1H NMR spectroscopy and dynamic light scattering, and the determination of the critical micelle concentration (cmc) is performed using pyrene fluorescence spectroscopy. For the different block copolypeptoids cmc values ranging from 0.6 × 10-6 M to 0.1 × 10-3 M are found. The tendency to form micelles increases with increasing hydrophobicity at the nitrogen side chain in the hydrophobic moiety. Furthermore, in the case of the same hydrophobic side chain, a decreasing hydrophilic/lipophilic balance leads to the formation of larger aggregates. The aggregates formed in the buffer are able to solubilize the hydrophobic model compounds Reichardt\\'s dye and pyrene, and exhibit versatile microenvironments. Final investigations about the cytotoxicity reveal that the block copolypeptoids are well tolerated by mammalian cells up to high concentrations.

  6. Body Composition and Anti-Neoplastic Treatment in Adult and Older Subjects - A Systematic Review.

    Science.gov (United States)

    Gérard, S; Bréchemier, D; Lefort, A; Lozano, S; Abellan Van Kan, G; Filleron, T; Mourey, L; Bernard-Marty, C; Rougé-Bugat, M E; Soler, V; Vellas, B; Cesari, M; Rolland, Y; Balardy, L

    2016-01-01

    The estimation of the risk of poor tolerance and overdose of antineoplastic agents protocols represents a major challenge in oncology, particularly in older patients. We hypothesize that age-related modifications of body composition (i.e. increased fat mass and decreased lean mass) may significantly affect tolerance to chemotherapy. We conducted a systematic review for the last 25 years (between 1990 and 2015), using US National library of Medicine Medline electronic bibliographic database and Embase database of cohorts or clinical trials exploring (i) the interactions of body composition (assessed by Dual X-ray Absorptiometry, Bioelectrical Impedance Analyses, or Computerized Tomography) with pharmacokinetics parameters, (ii) the tolerance to chemotherapy, and (iii) the consequences of chemotherapies or targeted therapies on body composition. Our search identified 1504 articles. After a selection (using pre-established criteria) on titles and abstract, 24 original articles were selected with 3 domains of interest: impact of body composition on pharmacokinetics (7 articles), relationship between body composition and chemotoxicity (14 articles), and effect of anti-cancer chemotherapy on body composition (11 articles). The selected studies suggested that pharmacokinetic was influenced by lean mass, that lower lean mass could be correlated with toxicity, and that sarcopenic patients experienced more toxicities that non-sarcopenic patients. Regarding fat mass, results were less conclusive. No studies specifically explored the topic of body composition in older cancer patients. Plausible pathophysiological pathways linking body composition, toxicity, and pharmacokinetics are sustained by the actual review. However, despite the growing number of older cancer patients, our review highlighted the lack of specific studies in the field of anti-neoplastic agents toxicity regarding body composition conducted in elderly.

  7. Bringing Radiotracing to Titanium-Based Antineoplastics: Solid Phase Radiosynthesis, PET and ex Vivo Evaluation of Antitumor Agent [45Ti](salan)Ti(dipic)

    DEFF Research Database (Denmark)

    Severin, Gregory; Nielsen, Carsten H.; Jensen, Andreas Tue Ingemann

    2015-01-01

    We present a novel solid-phase based 45Ti radiolabeling methodology and the implementation of 45Ti-PET in titanium-based antineoplastics using the showcase compound [45Ti](salan)Ti(dipic). This development is intended to allow elucidation of the biodistribution and pharmacokinetics of promising new...

  8. Accelerator mass spectrometry analysis of "1"4C-oxaliplatin concentrations in biological samples and "1"4C contents in biological samples and antineoplastic agents

    International Nuclear Information System (INIS)

    Toyoguchi, Teiko; Kobayashi, Takeshi; Konno, Noboru; Shiraishi, Tadashi; Kato, Kazuhiro; Tokanai, Fuyuki

    2015-01-01

    Accelerator mass spectrometry (AMS) is expected to play an important role in microdose trials. In this study, we measured the "1"4C concentration in "1"4C-oxaliplatin-spiked serum, urine and supernatant of fecal homogenate samples in our Yamagata University (YU) – AMS system. The calibration curves of "1"4C concentration in serum, urine and supernatant of fecal homogenate were linear (the correlation coefficients were ⩾0.9893), and the precision and accuracy was within the acceptance criteria. To examine a "1"4C content of water in three vacuum blood collection tubes and a syringe were measured. "1"4C was not detected from water in these devices. The mean "1"4C content in urine samples of 6 healthy Japanese volunteers was 0.144 dpm/mL, and the intra-day fluctuation of "1"4C content in urine from a volunteer was little. The antineoplastic agents are administered to the patients in combination. Then, "1"4C contents of the antineoplastic agents were quantitated. "1"4C contents were different among 10 antineoplastic agents; "1"4C contents of paclitaxel injection and docetaxel hydrate injection were higher than those of the other injections. These results indicate that our quantitation method using YU-AMS system is suited for microdosing studies and that measurement of baseline and co-administered drugs might be necessary for the studies in low concentrations.

  9. Accelerator mass spectrometry analysis of {sup 14}C-oxaliplatin concentrations in biological samples and {sup 14}C contents in biological samples and antineoplastic agents

    Energy Technology Data Exchange (ETDEWEB)

    Toyoguchi, Teiko, E-mail: tteiko@med.id.yamagata-u.ac.jp [Department of Pharmacy, Yamagata University Hospital, 2-2-2 Iida-Nishi, Yamagata-shi, Yamagata 990-9585 (Japan); Kobayashi, Takeshi; Konno, Noboru; Shiraishi, Tadashi [Department of Pharmacy, Yamagata University Hospital, 2-2-2 Iida-Nishi, Yamagata-shi, Yamagata 990-9585 (Japan); Kato, Kazuhiro; Tokanai, Fuyuki [Department of Physics, Faculty of Science, Yamagata University, 1-4-12 Kojirakawa-machi, Yamagata-shi, Yamagata 990-8560 (Japan)

    2015-10-15

    Accelerator mass spectrometry (AMS) is expected to play an important role in microdose trials. In this study, we measured the {sup 14}C concentration in {sup 14}C-oxaliplatin-spiked serum, urine and supernatant of fecal homogenate samples in our Yamagata University (YU) – AMS system. The calibration curves of {sup 14}C concentration in serum, urine and supernatant of fecal homogenate were linear (the correlation coefficients were ⩾0.9893), and the precision and accuracy was within the acceptance criteria. To examine a {sup 14}C content of water in three vacuum blood collection tubes and a syringe were measured. {sup 14}C was not detected from water in these devices. The mean {sup 14}C content in urine samples of 6 healthy Japanese volunteers was 0.144 dpm/mL, and the intra-day fluctuation of {sup 14}C content in urine from a volunteer was little. The antineoplastic agents are administered to the patients in combination. Then, {sup 14}C contents of the antineoplastic agents were quantitated. {sup 14}C contents were different among 10 antineoplastic agents; {sup 14}C contents of paclitaxel injection and docetaxel hydrate injection were higher than those of the other injections. These results indicate that our quantitation method using YU-AMS system is suited for microdosing studies and that measurement of baseline and co-administered drugs might be necessary for the studies in low concentrations.

  10. Self-assembled tethered bimolecular lipid membranes.

    Science.gov (United States)

    Sinner, Eva-Kathrin; Ritz, Sandra; Naumann, Renate; Schiller, Stefan; Knoll, Wolfgang

    2009-01-01

    This chapter describes some of the strategies developed in our group for designing, constructing and structurally and functionally characterizing tethered bimolecular lipid membranes (tBLM). We introduce this platform as a novel model membrane system that complements the existing ones, for example, Langmuir monolayers, vesicular liposomal dispersions and bimolecular ("black") lipid membranes. Moreover, it offers the additional advantage of allowing for studies of the influence of membrane structure and order on the function of integral proteins, for example, on how the composition and organization of lipids in a mixed membrane influence the ion translocation activity of integral channel proteins. The first strategy that we introduce concerns the preparation of tethered monolayers by the self-assembly of telechelics. Their molecular architecture with a headgroup, a spacer unit (the "tether") and the amphiphile that mimics the lipid molecule allows them to bind specifically to the solid support thus forming the proximal layer of the final architecture. After fusion of vesicles that could contain reconstituted proteins from a liposomal dispersion in contact to this monolayer the tethered bimolecular lipid membrane is obtained. This can then be characterized by a broad range of surface analytical techniques, including surface plasmon spectroscopies, the quartz crystal microbalance, fluorescence and IR spectroscopies, and electrochemical techniques, to mention a few. It is shown that this concept allows for the construction of tethered lipid bilayers with outstanding electrical properties including resistivities in excess of 10 MOmega cm2. A modified strategy uses the assembly of peptides as spacers that couple covalently via their engineered sulfhydryl or lipoic acid groups at the N-terminus to the employed gold substrate, while their C-terminus is being activated afterward for the coupling of, for example, dimyristoylphosphatidylethanol amine (DMPE) lipid molecules

  11. Influence of the state of phase of lipid bilayer on the exposure of glucose residues on the surface of liposomes.

    Science.gov (United States)

    Villalva, Denise Gradella; Giansanti, Luisa; Mauceri, Alessandro; Ceccacci, Francesca; Mancini, Giovanna

    2017-11-01

    The presence of carbohydrate-binding proteins (i.e. lectins) on the surface of various bacterial strains and their overexpression in some tumor tissues makes the use of glycosylated liposomes a promising approach for the specific drug delivery in antibacterial and anti-cancer therapies. However, the functionalization of liposome surface with sugar moieties by glycosylated amphiphiles does not ensure the binding of sugar-coated vesicles with lectins. In fact, the composition and properties of lipid bilayer play a pivotal role in the exposure of sugar residues and in the interaction with lectins. The influence of the length of the hydrophilic spacer that links the sugar to liposome surface and of the presence of saturated or unsaturated phospholipids in the lipid bilayer on the ability of glucosylated liposomes to interact with a model lectin, Concanavalin A, was investigated. Our results demonstrate that both the chain length and the prensece of unsaturation, parameters that strongly affect the fluidity of the lipid bilayer, affect agglutination. In particular, agglutination is favored when liposomes are in the gel phase within a defined range of temperature. Moreover, the obtained results confirm that the length of the PEG spacer, that influences both lipid organization and the exposure of sugar moieties to the bulk, plays a crucial role in liposome/lectin interaction. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Impact of two different saponins on the organization of model lipid membranes.

    Science.gov (United States)

    Korchowiec, Beata; Gorczyca, Marcelina; Wojszko, Kamila; Janikowska, Maria; Henry, Max; Rogalska, Ewa

    2015-10-01

    Saponins, naturally occurring plant compounds are known for their biological and pharmacological activity. This activity is strongly related to the amphiphilic character of saponins that allows them to aggregate in aqueous solution and interact with membrane components. In this work, Langmuir monolayer techniques combined with polarization modulation infrared reflection-absorption spectroscopy (PM-IRRAS) and Brewster angle microscopy were used to study the interaction of selected saponins with lipid model membranes. Two structurally different saponins were used: digitonin and a commercial Merck Saponin. Membranes of different composition, namely, cholesterol, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine or 1,2-dipalmitoyl-sn-glycero-3-phospho-rac-(1-glycerol) were formed at the air/water and air/saponin solution interfaces. The saponin-lipid interaction was characterized by changes in surface pressure, surface potential, surface morphology and PM-IRRAS signal. Both saponins interact with model membranes and change the physical state of membranes by perturbing the lipid acyl chain orientation. The changes in membrane fluidity were more significant upon the interaction with Merck Saponin. A higher affinity of saponins for cholesterol than phosphatidylglycerols was observed. Moreover, our results indicate that digitonin interacts strongly with cholesterol and solubilize the cholesterol monolayer at higher surface pressures. It was shown, that digitonin easily penetrate to the cholesterol monolayer and forms a hydrogen bond with the hydroxyl groups. These findings might be useful in further understanding of the saponin action at the membrane interface and of the mechanism of membrane lysis. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Anti-inflammatory polymersomes of redox-responsive polyprodrug amphiphiles with inflammation-triggered indomethacin release characteristics.

    Science.gov (United States)

    Tan, Jiajia; Deng, Zhengyu; Liu, Guhuan; Hu, Jinming; Liu, Shiyong

    2018-03-21

    Inflammation serves as a natural defense mechanism to protect living organisms from infectious diseases. Nonsteroidal anti-inflammatory drugs (NSAIDs) can help relieve inflammatory reactions and are clinically used to treat pain, fever, and inflammation, whereas long-term use of NSAIDs may lead to severe side effects including gastrointestinal damage and cardiovascular toxicity. Therefore, it is of increasing importance to configure new dosing strategies and alleviate the side effects of NSAIDs. Towards this goal, glutathione (GSH)-responsive disulfide bonds and hydrogen peroxide (H 2 O 2 )-reactive phenylboronic ester linkages were utilized as triggering moieties in this work to design redox-responsive prodrug monomers and polyprodrug amphiphiles based on indomethacin (IND) drug. Note that IND is a widely prescribed NSAID in the clinic. Starting from three types of redox-reactive IND prodrug monomers, redox-responsive polyprodrug amphiphiles were synthesized through reversible addition-fragmentation chain transfer (RAFT) polymerizations of prodrug monomers using poly(ethylene oxide) (PEO)-based macroRAFT agent. The resultant polyprodrug amphiphiles with high IND loading contents (>33 wt%) could self-assemble into polymersomes with PEO shielding coronas and redox-responsive bilayer membranes composed of IND prodrugs. Upon incubation with GSH or H 2 O 2 , controlled release of intact IND in the active form from polyprodrug polymersomes was actuated by GSH-mediated disulfide cleavage reaction and H 2 O 2 -mediated oxidation of phenylboronic ester moieties, respectively, followed by self-immolative degradation events. Furthermore, in vitro studies at the cellular level revealed that redox-responsive polymersomes could efficiently relieve inflammatory responses induced by lipopolysaccharide (LPS) in RAW264.7 macrophage cells. Copyright © 2018. Published by Elsevier Ltd.

  14. Self-assembled structures of amphiphilic ionic block copolymers: Theory, self-consistent field modeling and experiment

    NARCIS (Netherlands)

    Borisov, O.V.; Zhulina, E.B.; Leermakers, F.A.M.; Muller, A.H.E.

    2011-01-01

    We present an overview of statistical thermodynamic theories that describe the self-assembly of amphiphilic ionic/hydrophobic diblock copolymers in dilute solution. Block copolymers with both strongly and weakly dissociating (pH-sensitive) ionic blocks are considered. We focus mostly on structural

  15. Graphene oxide-enhanced sol-gel transition sensitivity and drug release performance of an amphiphilic copolymer-based nanocomposite

    Science.gov (United States)

    Hu, Huawen; Wang, Xiaowen; Lee, Ka I; Ma, Kaikai; Hu, Hong; Xin, John H.

    2016-01-01

    We report the fabrication of a highly sensitive amphiphilic copolymer-based nanocomposite incorporating with graphene oxide (GO), which exhibited a low-intensity UV light-triggered sol-gel transition. Non-cytotoxicity was observed for the composite gels after the GO incorporation. Of particular interest were the microchannels that were formed spontaneously within the GO-incorporated UV-gel, which expedited sustained drug release. Therefore, the present highly UV-sensitive, non-cytotoxic amphiphilic copolymer-based composites is expected to provide enhanced photothermal therapy and chemotherapy by means of GO’s unique photothermal properties, as well as through efficient passive targeting resulting from the sol-gel transition characteristic of the copolymer-based system with improved sensitivity, which thus promises the enhanced treatment of patients with cancer and other diseases. PMID:27539298

  16. Micellar Surfactant Association in the Presence of a Glucoside-based Amphiphile Detected via High-Throughput Small Angle X-ray Scattering

    Energy Technology Data Exchange (ETDEWEB)

    Stanic, Vesna [Brazilian Synchrotron Light Source, Campinas (Brazil); Broadbent, Charlotte [Columbia Univ., New York, NY (United States). Engineering Dept.; DiMasi, Elaine [Brookhaven National Lab. (BNL), Upton, NY (United States). Photon Sciences Division; Galleguillos, Ramiro [Lubrizol Advanced Materials, Cleveland, OH (United States); Woodward, Valerie [Lubrizol Advanced Materials, Cleveland, OH (United States)

    2016-11-14

    The interactions of mixtures of anionic and amphoteric surfactants with sugar amphiphiles were studied via high throughput small angle x-ray scattering (SAXS). The sugar amphiphile was composed of Caprate, Caprylate, and Oleate mixed ester of methyl glucoside, MeGCCO. Optimal surfactant interactions are sought which have desirable physical properties, which must be identified in a cost effective manner that can access the large phase space of possible molecular combinations. X-ray scattering patterns obtained via high throughput SAXS can probe a combinatorial sample space and reveal the incorporation of MeGCCO into the micelles and the molecular associations between surfactant molecules. Such data make it possible to efficiently assess the effects of the new amphiphiles in the formulation. A specific finding of this study is that formulations containing comparatively monodisperse and homogeneous surfactant mixtures can be reliably tuned by addition of NaCl, which swells the surfactant micelles with a monotonic dependence on salt concentration. In contrast, the presence of multiple different surfactants destroys clear correlations with NaCl concentration, even in otherwise similar series of formulations.

  17. Modulation of Cyclodextrin Particle Amphiphilic Properties to Stabilize Pickering Emulsion.

    Science.gov (United States)

    Xi, Yongkang; Luo, Zhigang; Lu, Xuanxuan; Peng, Xichun

    2018-01-10

    Cyclodextrins have been proven to form complexes with linear oil molecules and stabilize emulsions. Amphiphilic properties of cyclodextrin particles were modulated through esterification reaction between β-cyclodextrin (β-CD) and octadecenyl succinic anhydride (ODSA) under alkaline conditions. ODS-β-CD particles with degree of substitution (DS) of 0.003, 0.011, and 0.019 were obtained. The introduced hydrophobic long chain that was linked within β-CD cavity led to the change of ODS-β-CD in terms of morphological structure, surface charge density, size, and contact angle, upon which the properties and stability of the emulsions stabilized by ODS-β-CD were highly dependent. The average diameter of ODS-β-CD particles ranged from 449 to 1484 nm. With the DS increased from 0.003 to 0.019, the contact angle and absolute zeta potential value of these ODS-β-CD particles improved from 25.7° to 47.3° and 48.1 to 62.8 mV, respectively. The cage structure of β-CD crystals was transformed to channel structure, then further to amorphous structure after introduction of the octadecenyl succinylation chain. ODS-β-CD particles exhibited higher emulsifying ability compared to β-CD. The resulting Pickering emulsions formed by ODS-β-CD particles were more stable during storage. This study investigates the ability of these ODS-β-CD particles to stabilize oil-in-water emulsions with respect to their amphiphilic character and structural properties.

  18. A spectroscopic method to estimate the binding potency of amphiphile assemblies

    Czech Academy of Sciences Publication Activity Database

    Gauger, D. R.; Andrushchenko, Valery; Bouř, Petr; Pohle, W.

    2010-01-01

    Roč. 398, č. 2 (2010), s. 1109-1123 ISSN 1618-2642 R&D Projects: GA ČR GA203/06/0420; GA ČR GA202/07/0732; GA ČR GAP208/10/0559; GA AV ČR IAA400550702; GA AV ČR IAA400550701 Institutional research plan: CEZ:AV0Z40550506 Keywords : miccels * amphiphile assemblies * molecular dynamics * infrared spectroscopy Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.841, year: 2010

  19. Effects of solubilization of short and medium-chain molecules in the self-assembly of two amphiphilic drugs in solution

    International Nuclear Information System (INIS)

    Barbosa, Silvia; Cheema, Mohammad Arif; Siddiq, Mohammad; Taboada, Pablo; Mosquera, Victor

    2009-01-01

    The effect of short and medium chain length alcohols ethanol, propanol, and butanol on the thermodynamic properties of aqueous solutions of the ionic amphiphilic antidepressants imipramine and clomipramine hydrochlorides has been investigated at T = 293 K. Critical concentrations of the drugs were obtained from ultrasound velocity measurements. Experimental results have shown a strong dependence of the ultrasound velocity with the alcohol concentration and chain length. Differences in the aggregate properties of both amphiphiles arise from the presence of the extra Cl - substituent on the ring system of clomipramine. Density and ultrasound measurements have been used to obtain the apparent molar volumes, V φ , and isentropic apparent molar compressibilities, K φ(S) , for the aqueous drug/water-alcohol solutions. The distribution coefficient of the amount solubilized between water and the aggregates, K, has been determined using an indirect method based on the pseudo-phase model by using apparent molar volume values. This method allows the calculation of the distribution coefficients at concentrations below saturation. The standard molar Gibbs free energy change on transfer from the aqueous to the micellar, ΔG 0 , phase was calculated from the partition coefficient. The results have highlighted the structural differences between both amphiphiles

  20. Engineering and validation of a novel lipid thin film for biomembrane modeling in lipophilicity determination of drugs and xenobiotics

    Directory of Open Access Journals (Sweden)

    Ogbonna Udochi

    2009-09-01

    Full Text Available Abstract Background Determination of lipophilicity as a tool for predicting pharmacokinetic molecular behavior is limited by the predictive power of available experimental models of the biomembrane. There is current interest, therefore, in models that accurately simulate the biomembrane structure and function. A novel bio-device; a lipid thin film, was engineered as an alternative approach to the previous use of hydrocarbon thin films in biomembrane modeling. Results Retention behavior of four structurally diverse model compounds; 4-amino-3,5-dinitrobenzoic acid (ADBA, naproxen (NPX, nabumetone (NBT and halofantrine (HF, representing 4 broad classes of varying molecular polarities and aqueous solubility behavior, was investigated on the lipid film, liquid paraffin, and octadecylsilane layers. Computational, thermodynamic and image analysis confirms the peculiar amphiphilic configuration of the lipid film. Effect of solute-type, layer-type and variables interactions on retention behavior was delineated by 2-way analysis of variance (ANOVA and quantitative structure property relationships (QSPR. Validation of the lipid film was implemented by statistical correlation of a unique chromatographic metric with Log P (octanol/water and several calculated molecular descriptors of bulk and solubility properties. Conclusion The lipid film signifies a biomimetic artificial biological interface capable of both hydrophobic and specific electrostatic interactions. It captures the hydrophilic-lipophilic balance (HLB in the determination of lipophilicity of molecules unlike the pure hydrocarbon film of the prior art. The potentials and performance of the bio-device gives the promise of its utility as a predictive analytic tool for early-stage drug discovery science.

  1. QSPR modeling of octanol/water partition coefficient of antineoplastic agents by balance of correlations.

    Science.gov (United States)

    Toropov, Andrey A; Toropova, Alla P; Raska, Ivan; Benfenati, Emilio

    2010-04-01

    Three different splits into the subtraining set (n = 22), the set of calibration (n = 21), and the test set (n = 12) of 55 antineoplastic agents have been examined. By the correlation balance of SMILES-based optimal descriptors quite satisfactory models for the octanol/water partition coefficient have been obtained on all three splits. The correlation balance is the optimization of a one-variable model with a target function that provides both the maximal values of the correlation coefficient for the subtraining and calibration set and the minimum of the difference between the above-mentioned correlation coefficients. Thus, the calibration set is a preliminary test set. Copyright (c) 2009 Elsevier Masson SAS. All rights reserved.

  2. New solid state forms of antineoplastic 5-fluorouracil with anthelmintic piperazine

    Science.gov (United States)

    Moisescu-Goia, C.; Muresan-Pop, M.; Simon, V.

    2017-12-01

    The aim of the present study was to asses the formation of solid forms between the 5-fluorouracil chemotherapy drug and the anthelmintic piperazine. Two new solid forms of antineoplastic agent 5-fluorouracil with anthelmintic piperazine were obtained by liquid assisted ball milling and slurry crystallization methods. The Nsbnd H hydrogen bonding donors and C = O hydrogen bonding acceptors of 5-fluorouracil allow to form co-crystals with other drugs delivering improved properties for medical applications, as proved for other compounds of pharmaceutical interest. Both new solid forms were investigated using X-ray powder diffraction (XRD), differential thermal analysis (DTA) and Fourier transform infrared (FTIR) spectroscopy. The XRD results show that by both methods were successfully synthesized new solid forms of 5-fluorouracil with piperazine. According to FTIR results the form prepared by lichid assisted grinding process was obtained as co-crystal and the other one, prepared by slurry method, resulted as a salt.

  3. Repurposing Cationic Amphiphilic Antihistamines for Cancer Treatment

    DEFF Research Database (Denmark)

    Ellegaard, Anne-Marie; Dehlendorff, Christian; Vind, Anna C.

    2016-01-01

    Non-small cell lung cancer (NSCLC) is one of the deadliest cancers worldwide. In search for new NSCLC treatment options, we screened a cationic amphiphilic drug (CAD) library for cytotoxicity against NSCLC cells and identified several CAD antihistamines as inducers of lysosomal cell death. We...... then performed a cohort study on the effect of CAD antihistamine use on mortality of patients diagnosed with non-localized cancer in Denmark between 1995 and 2011. The use of the most commonly prescribed CAD antihistamine, loratadine, was associated with significantly reduced all-cause mortality among patients...... with non-localized NSCLC or any non-localized cancer when compared with use of non-CAD antihistamines and adjusted for potential confounders. Of the less frequently described CAD antihistamines, astemizole showed a similar significant association with reduced mortality as loratadine among patients with any...

  4. Postulating a dermal pathway for exposure to anti-neoplastic drugs among hospital workers. Applying a conceptual model to the results of three workplace surveys

    NARCIS (Netherlands)

    Kromhout, H.; Hoek, F.; Uitterhoeve, R.; Huijbers, R.; Overmars, R.F.; Anzion, R.; Vermeulen, R.

    2000-01-01

    Dermal exposure to anti-neoplastic drugs has been suggested as a potentially important route of exposure of hospital workers. Three small-scale workplace surveys were carried out in several hospitals focusing on contamination by leakage from IV infusion systems; contamination by spilled urine of

  5. Amphiphilic derivatives of (3β,17β)-3-hydroxyandrost-5-ene-17-carboxylic acid

    Czech Academy of Sciences Publication Activity Database

    Özdemir, Zülal; Bildziukevich, Uladzimir; Šaman, David; Havlíček, Libor; Rárová, L.; Navrátilová, L.; Wimmer, Zdeněk

    2017-01-01

    Roč. 128, DEC (2017), s. 58-67 ISSN 0039-128X R&D Projects: GA MŠk LD15012 Institutional support: RVO:61389030 ; RVO:61388963 Keywords : Amphiphile * Antimicrobial activity * Cytotoxicity * Diamine * Polyamine * Steroid Subject RIV: CC - Organic Chemistry; CC - Organic Chemistry (UOCHB-X) OBOR OECD: Organic chemistry Impact factor: 2.282, year: 2016

  6. Dynamic stability of nano-fibers self-assembled from short amphiphilic A6D peptides.

    Science.gov (United States)

    Nikoofard, Narges; Maghsoodi, Fahimeh

    2018-04-07

    Self-assembly of A 6 D amphiphilic peptides in explicit water is studied by using coarse-grained molecular dynamics simulations. It is observed that the self-assembly of randomly distributed A 6 D peptides leads to the formation of a network of nano-fibers. Two other simulations with cylindrical nano-fibers as the initial configuration show the dynamic stability of the self-assembled nano-fibers. As a striking feature, notable fluctuations occur along the axes of the nano-fibers. Depending on the number of peptides per unit length of the nano-fiber, flat-shaped bulges or spiral shapes along the nano-fiber axis are observed at the fluctuations. Analysis of the particle distribution around the nano-fiber indicates that the hydrophobic core and the hydrophilic shell of the nano-structure are preserved in both simulations. The size of the deformations and their correlation times are different in the two simulations. This study gives new insights into the dynamics of the self-assembled nano-structures of short amphiphilic peptides.

  7. Dynamic stability of nano-fibers self-assembled from short amphiphilic A6D peptides

    Science.gov (United States)

    Nikoofard, Narges; Maghsoodi, Fahimeh

    2018-04-01

    Self-assembly of A6D amphiphilic peptides in explicit water is studied by using coarse-grained molecular dynamics simulations. It is observed that the self-assembly of randomly distributed A6D peptides leads to the formation of a network of nano-fibers. Two other simulations with cylindrical nano-fibers as the initial configuration show the dynamic stability of the self-assembled nano-fibers. As a striking feature, notable fluctuations occur along the axes of the nano-fibers. Depending on the number of peptides per unit length of the nano-fiber, flat-shaped bulges or spiral shapes along the nano-fiber axis are observed at the fluctuations. Analysis of the particle distribution around the nano-fiber indicates that the hydrophobic core and the hydrophilic shell of the nano-structure are preserved in both simulations. The size of the deformations and their correlation times are different in the two simulations. This study gives new insights into the dynamics of the self-assembled nano-structures of short amphiphilic peptides.

  8. Sodium effect on self-organization of amphiphilic carboxylates: formation of structured micelles and superlattices.

    Science.gov (United States)

    Rosenlehner, Karin; Schade, Boris; Böttcher, Christoph; Jäger, Christof M; Clark, Timothy; Heinemann, Frank W; Hirsch, Andreas

    2010-08-16

    Not only the self-aggregation of dendritic polycarboxylates into structurally persistent micelles, but also that of the micelles themselves into superlattices is controlled by alkali-metal counterions and shows a pronounced sodium effect. Our combined experimental and computational work has revealed the formation of superlattices for the first time. The behavior of a variety of amphiphilic carboxylates and the different effects of the alkali cations Li(+), Na(+), and K(+) have been investigated by conductivity measurements, cryogenic transmission electron microscopy (cryo-TEM), and molecular-dynamics (MD) simulations. Together, these show that sodium salts of the amphiphiles give the most stable micelles, followed by lithium and potassium. Our results suggest that ion multiplets in bridging positions, rather than contact ion pairs, are responsible for the enhanced stability and the formation of hexagonally ordered superlattices with sodium counterions. Potassium ions do not form such ion multiplets and cannot therefore induce aggregation of the micelles. This sodium effect has far-reaching consequences for a large number of biological and technical systems and sheds new light on the origin of specific-ion effects.

  9. Injectable-antineoplastic-drug practices in Michigan hospitals.

    Science.gov (United States)

    Cohen, I A; Newland, S J; Kirking, D M

    1987-05-01

    Practices related to parenteral (injectable) antineoplastic drugs (PADs) in Michigan hospitals were surveyed. All hospitals in Michigan were surveyed to assess compliance with American Society of Hospital Pharmacists (ASHP) and Occupational Safety and Health Administration (OSHA) recommendations related to PADs. Other PAD-related practice issues not covered within those guidelines were also studied. Surveys were mailed to the pharmacy directors of the state's 192 acute-care hospitals. Included were questions concerning policies and procedures for ordering, storing, preparing, handling, labeling, transporting, administering, and disposing of PADs. Questions concerning staff education, spill cleanup, and personnel issues were also included. A total of 169 questionnaires were returned, yielding a response rate of 88%. Of those respondents, 132 indicated that they prepare PAD doses for inpatients. Adherence rates were high for several of the PAD-preparation recommendations, including handwashing (97%) and gloving (98.5%). Rates for gowning (71.2%), labeling of PAD doses as biohazards (chemical hazards) (73.5%), and use of Class II biological-safety cabinets (71.2%) were less favorable. Practice areas with relatively poor adherence rates included use of plastic-backed absorbent pads under PAD preparation areas (53.8%), storing PADs separately from other drugs (48.5%), informing prospective employees of potential risks of handling PADs (36.4%), availability of spill kits (36.4%), and attaching and priming i.v. tubing before adding PADs to i.v. containers (5.4%). Many pharmacy departments in Michigan hospitals can substantially improve their adherence to ASHP and OSHA recommendations related to PADs.

  10. Amphiphilic poly(ether ester amide) multiblock copolymers as biodegradable matrices for the controlled release of proteins

    NARCIS (Netherlands)

    Bezemer, J.M.; Oude Weme, P.; Grijpma, Dirk W.; Dijkstra, Pieter J.; van Blitterswijk, Clemens; Feijen, Jan

    2000-01-01

    Amphiphilic poly(ether ester amide) (PEEA) multiblock copolymers were synthesized by polycondensation in the melt from hydrophilic poly(ethylene glycol) (PEG), 1,4-dihydroxybutane and short bisester-bisamide blocks. These amide blocks were prepared by reaction of 1,4-diaminobutane with dimethyl

  11. Molecular, dynamic, and structural origin of inhomogeneous magnetization transfer in lipid membranes.

    Science.gov (United States)

    Swanson, Scott D; Malyarenko, Dariya I; Fabiilli, Mario L; Welsh, Robert C; Nielsen, Jon-Fredrik; Srinivasan, Ashok

    2017-03-01

    To elucidate the dynamic, structural, and molecular properties that create inhomogeneous magnetization transfer (ihMT) contrast. Amphiphilic lipids, lamellar phospholipids with cholesterol, and bovine spinal cord (BSC) specimens were examined along with nonlipid systems. Magnetization transfer (MT), enhanced MT (eMT, obtained with double-sided radiofrequency saturation), ihMT (MT - eMT), and dipolar relaxation, T 1D , were measured at 2.0 and 11.7 T. The amplitude of ihMT ratio (ihMTR) is positively correlated with T 1D values. Both ihMTR and T 1D increase with increasing temperature in BSC white matter and in phospholipids and decrease with temperature in other lipids. Changes in ihMTR with temperature arise primarily from alterations in MT rather than eMT. Spectral width of MT, eMT, and ihMT increases with increasing carbon chain length. Concerted motions of phospholipids in white matter decrease proton spin diffusion leading to increased proton T 1D times and increased ihMT amplitudes, consistent with decoupling of Zeeman and dipolar spin reservoirs. Molecular specificity and dynamic sensitivity of ihMT contrast make it a suitable candidate for probing myelin membrane disorders. Magn Reson Med 77:1318-1328, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

  12. Gd-DTPA-Dopamine-Bisphytanyl Amphiphile: Synthesis, Characterisation and Relaxation Parameters of the Nanoassemblies and Their Potential as MRI Contrast Agents.

    Science.gov (United States)

    Gupta, Abhishek; Willis, Scott A; Waddington, Lynne J; Stait-Gardner, Tim; de Campo, Liliana; Hwang, Dennis W; Kirby, Nigel; Price, William S; Moghaddam, Minoo J

    2015-09-28

    Here, a new amphiphilic magnetic resonance imaging (MRI) contrast agent, a Gd(III)-chelated diethylenetriaminepentaacetic acid conjugated to two branched alkyl chains via a dopamine spacer, Gd-DTPA-dopamine-bisphytanyl (Gd-DTPA-Dop-Phy), which is readily capable of self-assembling into liposomal nanoassemblies upon dispersion in an aqueous solution, is reported. In vitro relaxivities of the dispersions were found to be much higher than Magnevist, a commercially available contrast agent, at 0.47 T but comparable at 9.40 T. Analysis of variable temperature (17)O NMR transverse relaxation measurements revealed the water exchange of the nanoassemblies to be faster than that previously reported for paramagnetic liposomes. Molecular reorientation dynamics were probed by (1)H NMRD profiles using a classical inner and outer sphere relaxation model and a Lipari-Szabo "model-free" approach. High payloads of Gd(III) ions in the liposomal nanoassemblies made solely from the Gd-DTPA-Dop-Phy amphiphiles, in combination with slow molecular reorientation and fast water exchange makes this novel amphiphile a suitable candidate to be investigated as an advanced MRI contrast agent. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Flat-on ambipolar triphenylamine/C60 nano-stacks formed from the self-organization of a pyramid-sphere-shaped amphiphile.

    Science.gov (United States)

    Liang, Wei-Wei; Huang, Chi-Feng; Wu, Kuan-Yi; Wu, San-Lien; Chang, Shu-Ting; Cheng, Yen-Ju; Wang, Chien-Lung

    2016-04-21

    A giant amphiphile, which is constructed with an amorphous nano-pyramid (triphenylamine, TPA) and a crystalline nano-sphere (C 60 ), was synthesized. Structural characterization indicates that this pyramid-sphere-shaped amphiphile ( TPA-C 60 ) forms a solvent-induced ordered phase, in which the two constituent units self-assemble into alternating stacks of two-dimensional (2D) TPA and C 60 nano-sheets. Due to the complexity of the molecular structure and the amorphous nature of the nano-pyramid, phase formation was driven by intermolecular C 60 -C 60 interactions and the ordered phase could not be reformed from the TPA-C 60 melt. Oriented crystal arrays of TPA-C 60 , which contain flat-on TPA/C 60 nano-stacks, can be obtained via a PDMS-assisted crystallization (PAC) technique. The flat-on dual-channel supramolecular structure of TPA-C 60 delivered ambipolar and balanced charge-transport characteristics with an average μ e of 2.11 × 10 -4 cm 2 V -1 s -1 and μ h of 3.37 × 10 -4 cm 2 V -1 s -1 . The anisotropic charge-transport ability of the pyramid-sphere-shaped amphiphile was further understood based on the lattice structure and the lattice orientation of TPA-C 60 revealed from electron diffraction analyses.

  14. LipidPedia: a comprehensive lipid knowledgebase.

    Science.gov (United States)

    Kuo, Tien-Chueh; Tseng, Yufeng Jane

    2018-04-10

    Lipids are divided into fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, saccharolipids, sterols, prenol lipids and polyketides. Fatty acyls and glycerolipids are commonly used as energy storage, whereas glycerophospholipids, sphingolipids, sterols and saccharolipids are common used as components of cell membranes. Lipids in fatty acyls, glycerophospholipids, sphingolipids and sterols classes play important roles in signaling. Although more than 36 million lipids can be identified or computationally generated, no single lipid database provides comprehensive information on lipids. Furthermore, the complex systematic or common names of lipids make the discovery of related information challenging. Here, we present LipidPedia, a comprehensive lipid knowledgebase. The content of this database is derived from integrating annotation data with full-text mining of 3,923 lipids and more than 400,000 annotations of associated diseases, pathways, functions, and locations that are essential for interpreting lipid functions and mechanisms from over 1,400,000 scientific publications. Each lipid in LipidPedia also has its own entry containing a text summary curated from the most frequently cited diseases, pathways, genes, locations, functions, lipids and experimental models in the biomedical literature. LipidPedia aims to provide an overall synopsis of lipids to summarize lipid annotations and provide a detailed listing of references for understanding complex lipid functions and mechanisms. LipidPedia is available at http://lipidpedia.cmdm.tw. yjtseng@csie.ntu.edu.tw. Supplementary data are available at Bioinformatics online.

  15. Amphiphilic invertible polymers: Self-assembly into functional materials driven by environment polarity

    Science.gov (United States)

    Hevus, Ivan

    Stimuli-responsive polymers adapt to environmental changes by adjusting their chain conformation in a fast and reversible way. Responsive polymeric materials have already found use in electronics, coatings industry, personal care, and bio-related areas. The current work aims at the development of novel responsive functional polymeric materials by manipulating environment-dependent self-assembly of a new class of responsive macromolecules strategically designed in this study,—amphiphilic invertible polymers (AIPs). Environment-dependent micellization and self-assembly of three different synthesized AIP types based on poly(ethylene glycol) as a hydrophilic fragment and varying hydrophobic constituents was demonstrated in polar and nonpolar solvents, as well as on the surfaces and interfaces. With increasing concentration, AIP micelles self-assemble into invertible micellar assemblies composed of hydrophilic and hydrophobic domains. Polarity-responsive properties of AIPs make invertible micellar assemblies functional in polar and nonpolar media including at interfaces. Thus, invertible micellar assemblies solubilize poorly soluble substances in their interior in polar and nonpolar solvents. In a polar aqueous medium, a novel stimuli-responsive mechanism of drug release based on response of AIP-based drug delivery system to polarity change upon contact with the target cell has been established using invertible micellar assemblies loaded with curcumin, a phytochemical drug. In a nonpolar medium, invertible micellar assemblies were applied simultaneously as nanoreactors and stabilizers for size-controlled synthesis of silver nanoparticles stable in both polar and nonpolar media. The developed amphiphilic nanosilver was subsequently used as seeds to promote anisotropic growth of CdSe semiconductor nanoparticles that have potential in different applications ranging from physics to medicine. Amphiphilic invertible polymers were shown to adsorb on the surface of silica

  16. Intracellular degradation of microspheres based on cross-linked dextran hydrogels or amphiphilic block copolymers: A comparative Raman microscopy study

    Science.gov (United States)

    van Manen, Henk-Jan; van Apeldoorn, Aart A; Verrijk, Ruud; van Blitterswijk, Clemens A; Otto, Cees

    2007-01-01

    Micro- and nanospheres composed of biodegradable polymers show promise as versatile devices for the controlled delivery of biopharmaceuticals. Whereas important properties such as drug release profiles, biocompatibility, and (bio)degradability have been determined for many types of biodegradable particles, information about particle degradation inside phagocytic cells is usually lacking. Here, we report the use of confocal Raman microscopy to obtain chemical information about cross-linked dextran hydrogel microspheres and amphiphilic poly(ethylene glycol)-terephthalate/poly(butylene terephthalate) (PEGT/PBT) microspheres inside RAW 264.7 macrophage phagosomes. Using quantitative Raman microspectroscopy, we show that the dextran concentration inside phagocytosed dextran microspheres decreases with cell incubation time. In contrast to dextran microspheres, we did not observe PEGT/PBT microsphere degradation after 1 week of internalization by macrophages, confirming previous studies showing that dextran microsphere degradation proceeds faster than PEGT/PBT degradation. Raman microscopy further showed the conversion of macrophages to lipid-laden foam cells upon prolonged incubation with both types of microspheres, suggesting that a cellular inflammatory response is induced by these biomaterials in cell culture. Our results exemplify the power of Raman microscopy to characterize microsphere degradation in cells and offer exciting prospects for this technique as a noninvasive, label-free optical tool in biomaterials histology and tissue engineering. PMID:17722552

  17. Hydrophobic cotton textile surfaces using an amphiphilic graphene oxide (GO) coating

    International Nuclear Information System (INIS)

    Tissera, Nadeeka D.; Wijesena, Ruchira N.; Perera, J. Rangana; Nalin de Silva, K.M.; Amaratunge, Gehan A.J.

    2015-01-01

    Graphical abstract: - Highlights: • Different GO dispersions were prepared by sonicating different amounts of GO in water. Degree of exfoliation of these GO sheets in water was analyzed using Atomic Force Microscopy (AFM). • AFM results obtained showed higher the GO concentration on water more the size of GO sheets and lesser the degree of exfoliation. • GO with different amounts was deposited on cotton fabric using simple dyeing method. • High GO loading on cotton increase the surface area coverage of the textile fibers with GO sheets. This led to less edge to mid area ratio of grafted GO sheets. • As contribution of mid area of GO increase on fiber surface cotton fabric becomes more hydrophobic. • Amphiphilic property of GO sheets was used to lower the surface energy of the cotton fibers leading to hydrophobic property. - Abstract: We report for the first time hydrophobic properties on cotton fabric successfully achieved by grafting graphene oxide on the fabric surface, using a dyeing method. Graphite oxide synthesized by oxidizing natural flake graphite employing improved Hummer's method showed an inter layer spacing of ∼1 nm from XRD. Synthesized graphite oxide was exfoliated in water using ultrasound energy to obtain graphene oxide (GO). AFM data obtained for the graphene oxide dispersed in an aqueous medium revealed a non-uniform size distribution. FTIR characterization of the synthesized GO sheets showed both hydrophilic and hydrophobic functional groups present on the nano sheets giving them an amphiphilic property. GO flakes of different sizes were successfully grafted on to a cotton fabric surface using a dip dry method. Loading different amounts of graphene oxide on the cotton fiber surface allowed the fabric to demonstrate different degrees of hydrophobicity. The highest observed water contact angle was at 143° with the highest loading of graphene oxide. The fabric surfaces grafted with GO also exhibits adhesive type hydrophobicity

  18. Peroxisome Proliferator-Activated Receptors (PPARs as Potential Inducers of Antineoplastic Effects in CNS Tumors

    Directory of Open Access Journals (Sweden)

    Lars Tatenhorst

    2008-01-01

    Full Text Available The peroxisome proliferator-activated receptors (PPARs are ligand-inducible transcription factors which belong to the superfamily of nuclear hormone receptors. In recent years it turned out that natural as well as synthetic PPAR agonists exhibit profound antineoplastic as well as redifferentiation effects in tumors of the central nervous system (CNS. The molecular understanding of the underlying mechanisms is still emerging, with partially controverse findings reported by a number of studies dealing with the influence of PPARs on treatment of tumor cells in vitro. Remarkably, studies examining the effects of these drugs in vivo are just beginning to emerge. However, the agonists of PPARs, in particular the thiazolidinediones, seem to be promising candidates for new approaches in human CNS tumor therapy.

  19. Multicompartment micellar aggregates of linear ABC amphiphiles in solvents selective for the C block: A Monte Carlo simulation

    KAUST Repository

    Zhu, Yutian

    2012-01-01

    In the current study, we applied the Monte Carlo method to study the self-assembly of linear ABC amphiphiles composed of two solvophobic A and B blocks and a solvophilic C block. A great number of multicompartment micelles are discovered from the simulations and the detailed phase diagrams for the ABC amphiphiles with different block lengths are obtained. The simulation results reveal that the micellar structure is largely controlled by block length, solvent quality, and incompatibility between the different block types. When the B block is longer than or as same as the terminal A block, a rich variety of micellar structures can be formed from ABC amphiphiles. By adjusting the solvent quality or incompatibility between the different block types, multiple morphological transitions are observed. These morphological sequences are well explained and consistent with all the previous experimental and theoretical studies. Despite the complexity of the micellar structures and morphological transitions observed for the self-assembly of ABC amphiphiles, two important common features of the phase behavior are obtained. In general, the micellar structures obtained in the current study can be divided into zero-dimensional (sphere-like structures, including bumpy-surfaced spheres and sphere-on-sphere structures), one-dimensional (cylinder-like structures, including rod and ring structures), two-dimensional (layer-like structures, including disk, lamella and worm-like and hamburger structures) and three-dimensional (vesicle) structures. It is found that the micellar structures transform from low- to high- dimensional structures when the solvent quality for the solvophobic blocks is decreased. In contrast, the micellar structures transform from high- to low-dimensional structures as the incompatibility between different block types increases. Furthermore, several novel micellar structures, such as the CBABC five-layer vesicle, hamburger, CBA three-layer ring, wormlike shape with

  20. Synthesis and Anchoring of Antineoplastic Ferrocene and Phthalocyanine Derivatives on Water-Soluble Polymeric Drug Carriers Derived from Lysine and Aspartic Acid

    OpenAIRE

    Maree, M. David; Neuse, Eberhard W.; Erasmus, Elizabeth; Swarts, Jannie C.

    2007-01-01

    The general synthetic strategy towards water-soluble biodegradable drug carriers and the properties that they must have are discussed. The syntheses of water-soluble biodegradable copolymers of lysine and aspartic acid as potential drug-delivering devices, having amine-functionalised side chains are then described. Covalent anchoring of carboxylic acid derivatives of the antineoplastic ferrocene and photodynamically active phthalocyanine moieties to the amine-containing drug carrier copolymer...

  1. On the formation of lipid droplets in human adipocytes: the organization of the perilipin-vimentin cortex.

    Directory of Open Access Journals (Sweden)

    Hans Heid

    Full Text Available We report on the heterogeneity and diversity of lipid droplets (LDs in early stages of adipogenesis by elucidating the cell and molecular biology of amphiphilic and cytoskeletal proteins regulating and stabilizing the generation of LDs in human adipose cells. A plethora of distinct and differently sized LDs was detected by a brief application of adipocyte differentiation medium and additional short treatment with oleic acid. Using these cells and highly specific antibodies for LD-binding proteins of the perilipin (PLIN family, we could distinguish between endogenously derived LDs (endogenous LDs positive for perilipin from exogenously induced LDs (exogenous LDs positive for adipophilin, TIP47 and S3-12. Having optimized these stimulation conditions, we used early adipogenic differentiation stages to investigate small-sized LDs and concentrated on LD-protein associations with the intermediate-sized filament (IF vimentin. This IF protein was described earlier to surround lipid globules, showing spherical, cage-like structures. Consequently - by biochemical methods, by immunofluorescence microscopy and by electron- and immunoelectron microscopy - various stages of emerging lipid globules were revealed with perilipin as linking protein between LDs and vimentin. For this LD-PLIN-Vimentin connection, a model is now proposed, suggesting an interaction of proteins via opposed charged amino acid domains respectively. In addition, multiple sheaths of smooth endoplasmic reticulum cisternae surrounding concentrically nascent LDs are shown. Based on our comprehensive localization studies we present and discuss a novel pathway for the LD formation.

  2. Effect of ionizing radiation exposure in the morphology of modified HDPE with amphiphilic particles; Efeito da exposicao a radiacao ionizante na morfologia de PEAD modificado com particulas anfifilicas

    Energy Technology Data Exchange (ETDEWEB)

    Saldanha, Ana Luiza M. [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil); Vivas, Viviane; Zylberberg, Marcel P.; Silva, Tamara I.; Cardoso, Andre Luis V.; Pereira, Iaci M., E-mail: iacipere@gmail.com [Centro Tecnologico do Exercito (CTEx), Rio de Janeiro, RJ (Brazil); Patricio, Patricia S.O. [Centro Federal de Educacao Tecnologica de Minas Gerias (CEFET), Belo Horizonte, MG (Brazil)

    2015-07-01

    One of the techniques used to improve the properties of high performance polymers is the addition of hybrid particles in the polymer. In this context, amphiphilic particles were synthesized in order to provide surface characteristics that enhance the interaction of the interface with the polymeric matrix of high density polyethylene (HDPE). The amphiphilic particles were added to matrix of HDPE and the modified polymer composites were exposed to ionizing radiation (x-rays) for different times. The changes caused by exposure to ionizing radiation in the composite morphology was observed through the small angle x-ray technique. The results suggest that the addition of amphiphilic particles increased the stability of the composite to degradation by radiation. (author)

  3. Water ordering controls the dynamic equilibrium of micelle-fibre formation in self-assembly of peptide amphiphiles.

    Science.gov (United States)

    Deshmukh, Sanket A; Solomon, Lee A; Kamath, Ganesh; Fry, H Christopher; Sankaranarayanan, Subramanian K R S

    2016-08-24

    Understanding the role of water in governing the kinetics of the self-assembly processes of amphiphilic peptides remains elusive. Here, we use a multistage atomistic-coarse-grained approach, complemented by circular dichroism/infrared spectroscopy and dynamic light scattering experiments to highlight the dual nature of water in driving the self-assembly of peptide amphiphiles (PAs). We show computationally that water cage formation and breakage near the hydrophobic groups control the fusion dynamics and aggregation of PAs in the micellar stage. Simulations also suggest that enhanced structural ordering of vicinal water near the hydrophilic amino acids shifts the equilibrium towards the fibre phase and stimulates structure and order during the PA assembly into nanofibres. Experiments validate our simulation findings; the measured infrared O-H bond stretching frequency is reminiscent of an ice-like bond which suggests that the solvated water becomes increasingly ordered with time in the assembled peptide network, thus shedding light on the role of water in a self-assembly process.

  4. To Take or Not to Take With Meals? Unraveling Issues Related to Food Effects Labeling for Oral Antineoplastic Drugs.

    Science.gov (United States)

    Deng, Jiexin; Brar, Satjit S; Lesko, Lawrence J

    2017-12-02

    There has been controversy regarding whether bioavailability of certain oral oncology drugs should be maximized by taking these medications with food, irrespective of label instructions in the dosing and administration section. To provide insight into this controversy, we conducted an in-depth analysis for oral antineoplastic drugs approved by the Food and Drug Administration in 2000-2016 and identified important issues influencing food labeling decisions. Furthermore, a case study involving sonidegib, a drug approved for locally advanced basal cell carcinoma with a significant food effect on exposure, was used to demonstrate the consequences of failure to adhere to food label recommendations using drug-specific population pharmacokinetic and exposure-toxicity models. In 2000-2009, 80% (4 out of 5) of all approved oral antineoplastics with increased bioavailability in the fed state were labeled as "take on empty stomach." In contrast, we found that in 2010-2016 there is a greater diversity in food recommendations for drugs with increased bioavailability in the fed state. Currently, many oral oncology drugs are given with food to maximize their bioavailability; however, as seen from our case study of sonidegib, failure to fully adhere to label recommendations to either take with food or not could lead to adverse consequences in terms of safety and efficacy. © 2017, The American College of Clinical Pharmacology.

  5. Phase behavior of fluorocarbon and hydrocarbon double-chain hydroxylated and galactosylated amphiphiles and bolaamphiphiles. Long-term shelf-stability of their liposomes.

    Science.gov (United States)

    Clary, L; Gadras, C; Greiner, J; Rolland, J P; Santaella, C; Vierling, P; Gulik, A

    1999-06-01

    This paper describes the morphological characterization, by freeze-fracture electron microscopy, and the thermotropic phase behavior, by differential scanning calorimetry and/or X-ray scattering, of aqueous dispersions of various hydroxylated and galactosylated double-chain amphiphiles and bolaamphiphiles, several of them containing one or two hydrophobic fluorocarbon chains. Colloidal systems are observed in water with the hydroxylated hydrocarbon or fluorocarbon bolaamphiphiles only when they are dispersed with a co-amphiphile such as rac-1,2-dimyristoylphosphatidylcholine (DMPC) or rac-1,2-distearoylphosphatidylcholine (DSPC). Liposomes are formed providing the relative content of bolaamphiphiles does not exceed 20% mol. Most of these liposomes can be thermally sterilized and stored at room temperature for several months without any significant modification of their size and size distribution. The hydrocarbon galactosylated bolaamphiphile HO[C24][C12]Gal forms in water a lamellar phase (the gel to liquid-crystal phase transition is complete at 45 degrees C) and a Im3m cubic phase above 47 degrees C. The fluorocarbon HO[C24][F6C5]Gal analog displays a more complex and metastable phase behavior. The fluorinated non-bolaform galactosylated [F8C7][C16]AEGal and SerGal amphiphiles form lamellar phases in water. Low amounts (10% molar ratio) of the HO[C24][F6C5]Gal or HO[C24][C12]Gal bolaamphiphiles or of the single-headed [F8C7][C16]AEGal improve substantially the shelf-stability of reference phospholipon/cholesterol 2/1 liposomes. These liposomes when co-formulated with a single-headed amphiphile from the SerGal series are by far less stable.

  6. Near-infrared fluorescence imaging and photodynamic therapy with indocyanine green lactosome has antineoplastic effects for hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Takumi Tsuda

    Full Text Available Anticancer agents and operating procedures have been developed for hepatocellular carcinoma (HCC patients, but their prognosis remains poor. It is necessary to develop novel diagnostic and therapeutic strategies for HCC to improve its prognosis. Lactosome is a core-shell-type polymeric micelle, and enclosing labeling or anticancer agents into this micelle enables drug delivery. In this study, we investigated the diagnostic and therapeutic efficacies of indocyanine green (ICG-loaded lactosome for near-infrared fluorescence (NIF imaging and photodynamic therapy (PDT for HCC.The human HCC cell line HuH-7 was treated with ICG or ICG-lactosome, followed by PDT, and the cell viabilities were measured (in vitro PDT efficiency. For NIF imaging, HuH-7 cells were subcutaneously transplanted into BALB/c nude mice, followed by intravenous administration of ICG or ICG-lactosome. The transplanted animals were treated with PDT, and the antineoplastic effects were analyzed (in vivo PDT efficiency.PDT had toxic effects on HuH-7 cells treated with ICG-lactosome, but not ICG alone. NIF imaging revealed that the fluorescence of tumor areas in ICG-lactosome-treated animals was higher than that of contralateral regions at 24 h after injection and thereafter. PDT exerted immediate and continuous phototoxic effects in the transplanted mice treated with ICG-lactosome.Our results demonstrate that ICG-lactosome accumulated in xenograft tumors, and that PDT had antineoplastic effects on these malignant implants. NIF imaging and PDT with ICG-lactosome could be useful diagnostic and/or therapeutic strategies for HCC.

  7. Examining factors that influence the effectiveness of cleaning antineoplastic drugs from drug preparation surfaces: a pilot study.

    Science.gov (United States)

    Hon, Chun-Yip; Chua, Prescillia Ps; Danyluk, Quinn; Astrakianakis, George

    2014-06-01

    Occupational exposure to antineoplastic drugs has been documented to result in various adverse health effects. Despite the implementation of control measures to minimize exposure, detectable levels of drug residual are still found on hospital work surfaces. Cleaning these surfaces is considered as one means to minimize the exposure potential. However, there are no consistent guiding principles related to cleaning of contaminated surfaces resulting in hospitals to adopt varying practices. As such, this pilot study sought to evaluate current cleaning protocols and identify those factors that were most effective in reducing contamination on drug preparation surfaces. Three cleaning variables were examined: (1) type of cleaning agent (CaviCide®, Phenokil II™, bleach and chlorhexidine), (2) application method of cleaning agent (directly onto surface or indirectly onto a wipe) and (3) use of isopropyl alcohol after cleaning agent application. Known concentrations of antineoplastic drugs (either methotrexate or cyclophosphamide) were placed on a stainless steel swatch and then, systematically, each of the three cleaning variables was tested. Surface wipes were collected and quantified using high-performance liquid chromatography-tandem mass spectrometry to determine the percent residual of drug remaining (with 100% being complete elimination of the drug). No one single cleaning agent proved to be effective in completely eliminating all drug contamination. The method of application had minimal effect on the amount of drug residual. In general, application of isopropyl alcohol after the use of cleaning agent further reduced the level of drug contamination although measureable levels of drug were still found in some cases.

  8. Multicompartment micellar aggregates of linear ABC amphiphiles in solvents selective for the C block: A Monte Carlo simulation

    KAUST Repository

    Zhu, Yutian; Yu, Haizhou; Wang, Yongmei; Cui, Jie; Kong, Weixin; Jiang, Wei

    2012-01-01

    the simulations and the detailed phase diagrams for the ABC amphiphiles with different block lengths are obtained. The simulation results reveal that the micellar structure is largely controlled by block length, solvent quality, and incompatibility between

  9. Influence of corona structure on binding of an ionic surfactant in oppositely charged amphiphilic polyelectrolyte micelles

    Czech Academy of Sciences Publication Activity Database

    Delisavva, F.; Uchman, M.; Škvarla, J.; Wozniak, E.; Pavlova, Ewa; Šlouf, Miroslav; Garamus, V. M.; Procházka, K.; Štěpánek, M.

    2016-01-01

    Roč. 32, č. 16 (2016), s. 4059-4065 ISSN 0743-7463 R&D Projects: GA TA ČR(CZ) TE01020118; GA MŠk(CZ) LO1507 Institutional support: RVO:61389013 Keywords : amphiphilic polymers * polyelectrolyte * corona structure Subject RIV: CD - Macromolecular Chemistry Impact factor: 3.833, year: 2016

  10. Yolk–shell Fe3O4@SiO2@PMO: amphiphilic magnetic nanocomposites as an adsorbent and a catalyst with high efficiency and recyclability

    KAUST Repository

    Dai, Jinyu

    2017-01-20

    This study describes the preparation of a multifunctional adsorptive catalyst by the incorporation of ligand groups within the channels of magnetic amphiphilic nanocomposites and attached with Pd nanoparticles. It was clearly demonstrated that Pd2+ was adsorbed by ligand-functionalized materials in water, and then Pd2+ was coordinated with ligand groups. Finally, the Pd nanoparticles were produced via an in situ reduction of Pd2+ by ligand groups through a simple hydrothermal process. Moreover, amphiphilic nanomaterials are viewed as excellent collectors of hydrophobic contaminants in water. The immobilized catalytic active sites with ligand-functionalized nanocomposites were allowed for maximal exposure to the reactants with minimal leaching of the Pd nanoparticles. The unique amphiphilic nanocomposites enabled selective oxidation of alcohols to proceed efficiently in water under aerobic conditions. Moreover, this nanocomposite catalyst could be completely recovered using an external magnet due to the superparamagnetic behavior of Fe3O4 and can be recycled with sustained selectivity and activity.

  11. Maltose-neopentyl glycol (MNG) amphiphiles for solubilization, stabilization and crystallization of membrane proteins

    OpenAIRE

    Chae, Pil Seok; Rasmussen, Søren G. F.; Rana, Rohini; Gotfryd, Kamil; Chandra, Richa; Goren, Michael A.; Kruse, Andrew C.; Nurva, Shailika; Loland, Claus J.; Pierre, Yves; Drew, David; Popot, Jean-Luc; Picot, Daniel; Fox, Brian G.; Guan, Lan

    2010-01-01

    The understanding of integral membrane protein (IMP) structure and function is hampered by the difficulty of handling these proteins. Aqueous solubilization, necessary for many types of biophysical analysis, generally requires a detergent to shield the large lipophilic surfaces displayed by native IMPs. Many proteins remain difficult to study owing to a lack of suitable detergents. We introduce a class of amphiphiles, each of which is built around a central quaternary carbon atom derived from...

  12. Effect of corticosteroids on phlebitis induced by intravenous infusion of antineoplastic agents in rabbits.

    Science.gov (United States)

    Kohno, Emiko; Murase, Saori; Matsuyama, Kenji; Okamura, Noboru

    2009-08-06

    Phlebitis caused by intravenous infusion of antineoplastic agents is one of the critical problems when anticancer therapy is prolonged. We have already reported that both rapid infusion and dilution of the injection solution were effective methods for reducing phlebitis caused by vinorelbine (VNR) in rabbits. The aim of this study was to explore other practical methods for preventing phlebitis caused by VNR and doxorubicin (DXR) in a rabbit model. VNR is often used with cisplatin, and dexamethasone (DEX) has been co-administered for prevention of cisplatin-induced nausea. DXR is used with prednisolone (PSL) in the CHOP regimen for the treatment of non-Hodgkin's lymphoma. Therefore, the present study investigated the prevention of phlebitis due to VNR with DEX and that due to DXR with PSL. VNR and DXR were diluted with normal saline to prepare test solutions at concentrations of 0.6 mg/mL and 1.4 mg/mL, respectively. Each test solution was infused into the auricular veins of rabbits. Two days after VNR infusion and three days after DXR infusion, the veins were evaluated histopathologically. The effect of DEX on VNR-induced phlebitis was evaluated by infusion of DEX before or after VNR. The effect of PSL on DXR-induced phlebitis was similarly evaluated by co-infusion of PSL. The histopathological features of phlebitis caused by the antineoplastic agents differed between VNR and DXR: VNR did not cause the loss of venous endothelial cells, but caused inflammatory cell infiltration, edema, and epidermal degeneration. In contrast, DXR caused the loss of venous endothelial cells and chrondrocyte necrosis. Pre-treatment and post-treatment with DEX significantly decreased VNR-induced phlebitis compared with the control group and pre-treatment was particularly effective. Co-infusion of PSL also significantly decreased phlebitis caused by DXR, but its effect was less marked. The present findings suggested that pre-treatment with DEX may be a useful method for preventing

  13. Lipid peroxidation and Alzheimer’s disease: Key role of Amyloid-β

    Directory of Open Access Journals (Sweden)

    Kontush Anatol

    2006-01-01

    Full Text Available Increased lipid peroxidation and elevated oxidative stress represent well-established characteristics of Alzheimer’s disease (AD. Amyloid-β (Aβ peptide, a major component of amyloid plaques, can strongly influence oxidative processes. In aggregated form, Aβ has prooxidative properties, whereas in monomeric form it functions as an antioxidant. The antioxidative properties of monomeric Aβ are related to its ability to chelate transition metal ions, which are potent catalysts of oxidation. Aβ possesses an amphiphilic structure, associates with lipoproteins in vivo and may therefore function as a preventive antioxidant which protects lipoproteins from oxidation by transition metal ions. Increased production of Aβ in response to elevated oxidative stress has been documented in a number of in vitro studies, implying that production of monomeric Aβ as a lipoprotein antioxidant can be abnormally increased in response to elevated oxidative stress in aging. Subsequent accumulation of Aβ-metal aggregates, production of reactive oxygen species and toxic action to neuronal cells may represent a gain-of-function transformation and form temporal sequence of events in the development of AD.

  14. The Effects of Alkyl Chain Combinations on the Structural and Mechanical Properties of Biomimetic Ion Pair Amphiphile Bilayers

    Directory of Open Access Journals (Sweden)

    Cheng-hao Chen

    2017-10-01

    Full Text Available Ion pair amphiphile (IPA, a lipid-like complex composed of a pair of cationic and anionic surfactants, has great potentials in various pharmaceutical applications. In this work, we utilized molecular dynamics (MD simulation to systematically examine the structural and mechanical properties of the biomimetic bilayers consist of alkyltrimethyl-ammonium-alkylsulfate (CmTMA+-CnS− IPAs with various alkyl chain combinations. Our simulations show an intrinsic one-atom offset for the CmTMA+ and CnS− alignment, leading to the asymmetric index definition of ΔC = m − (n + 1. Larger |ΔC| gives rise to higher conformational fluctuations of the alkyl chains with the reduced packing order and mechanical strength. In contrast, increasing the IPA chain length enhances the van der Waals interactions within the bilayer and thus improves the bilayer packing order and mechanical properties. Further elongating the CmTMA+-CnS− alkyl chains to m and n ≥ 12 causes the liquid disorder to gel phase transition of the bilayer at 298 K, with the threshold membrane properties of 0.45 nm2 molecular area, deuterium order parameter value of 0.31, and effective bending rigidity of 20 kBT, etc. The combined results provide molecular insights into the design of biomimetic IPA bilayers with wide structural and mechanical characteristics for various applications.

  15. Tumor transfection after systemic injection of DNA lipid nanocapsules.

    Science.gov (United States)

    Morille, Marie; Passirani, Catherine; Dufort, Sandrine; Bastiat, Guillaume; Pitard, Bruno; Coll, Jean-Luc; Benoit, Jean-Pierre

    2011-03-01

    With the goal of generating an efficient vector for systemic gene delivery, a new kind of nanocarrier consisting of lipid nanocapsules encapsulating DOTAP/DOPE lipoplexes (DNA LNCs) was pegylated by the post-insertion of amphiphilic and flexible polymers. The aim of this surface modification was to create a long-circulating vector, able to circulate in the blood stream and efficient in transfecting tumoral cells after passive targeting by enhanced permeability and retention effect (EPR effect). PEG conformation, electrostatic features, and hydrophylicity are known to be important factors able to influence the pharmacokinetic behaviour of vectors. In this context, the surface structure characteristics of the newly pegylated DNA LNCs were studied by measuring electrophoretic mobility as a function of ionic strength in order to establish a correlation between surface properties and in vivo performance of the vector. Finally, thanks to this PEGylation, gene expression was measured up to 84-fold higher in tumor compared to other tested organs after intravenous injection. The present results indicate that PEGylated DNA LNCs are promising carriers for an efficient cancer gene therapy. Copyright © 2010 Elsevier Ltd. All rights reserved.

  16. Lamellar crystalline self-assembly behaviour and solid lipid nanoparticles of a palmityl prodrug analogue of Capecitabine—A chemotherapy agent

    Energy Technology Data Exchange (ETDEWEB)

    Gong, Xiaojuan; Moghaddam, Minoo J.; Sagnella, Sharon M.; Conn, Charlotte E.; Danon, Stephen J.; Waddington, Lynne J.; Drummond, Calum J. [CSIRO/MSE

    2014-09-24

    An amphiphile prodrug, 5'-deoxy-5-fluoro-N4-(palmityloxycarbonyl) cytidine or 5'-deoxy-5-fluoro-N4-(hexadecanaloxycarbonyl) cytidine (5-FCPal), consisting of the same head group as the commercially available chemotherapeutic agent Capecitabine, linked to a palmityl hydrocarbon chain via a carbamate bond is reported. Thermal analysis of this prodrug indicates that it melts at ~115 °C followed quickly by degradation beginning at ~120 °C. The neat solid 5-FCPal amphiphile acquires a lamellar crystalline arrangement with a d-spacing of 28.6 ± 0.3 Å, indicating interdigitation of the hydrocarbon chains. Under aqueous conditions, solid 5-FCPal is non-swelling and no lyotropic liquid crystalline phase formation is observed. In order to assess the in vitro toxicity and in vivo efficacy in colloidal form, solid lipid nanoparticles (SLNs) with an average size of ~700 nm were produced via high pressure homogenization. The in vitro toxicity of the 5-FCPal SLNs against several different cancer and normal cell types was assessed over a 48 h period, and IC50 values were comparable to those observed for Capecitabine. The in vivo efficacy of the 5-FCPal SLNs was then assessed against the highly aggressive mouse 4T1 breast cancer model. To do so, the prodrug SLNs were administered orally at 3 different dosages (0.1, 0.25, 0.5 mmol/mouse/day) and compared to Capecitabine delivered at the same dosages. After 21 days of receiving the treatments, the 0.5 mmol dose of 5-FCPal exhibited the smallest average tumour volume. Since 5-FCPal is activated in a similar manner to Capecitabine via a 3 step enzymatic pathway with the final step occurring preferentially at the tumour site, formulation of the prodrug into SLNs combines the advantage of selective, localized activation with the sustained release properties of nanostructured amphiphile self-assembly and multiple payload materials thereby potentially creating a more effective anticancer agent.

  17. Exciplex emission from amphiphilic polysilanes bearing ammonium moieties

    International Nuclear Information System (INIS)

    Yamaki, T.; Nakashiba, Y.; Asai, K.; Ishigure, K.; Shibata, H.

    1997-01-01

    We were the first to observe two emission bands in the visible region for some kinds of ammonium-type amphiphilic polysilanes both in solutions and in thin films. One, a broad emission band at 400-500 nm not due to a σ * →σ transition, was observed only for methylphenylsilane-based polymer solutions. The appearance of this low-energy emission is reasonably explained by considering the intramolecular exciplex formation between a Si-conjugated main chain and an ammonium site in the same monomer unit. The other, an emission band at the longer wavelength (around 560 nm), was found in the solvent-cast films where each molecule is randomly located, in addition to that observed for the solutions. This emission, which was not observed for the oriented LB films, is considered to originate from an intermolecular interaction. (orig.)

  18. Coating of reverse osmosis membranes with amphiphilic copolymers for biofouling control

    KAUST Repository

    Bucs, Szilard

    2017-05-30

    Surface coating of membranes may be a promising option to control biofilm development and biofouling impact on membrane performance of spiral-wound reverse osmosis (RO) systems. The objective of this study was to investigate the impact of an amphiphilic copolymer coating on biofilm formation and biofouling control. The coating was composed of both hydrophilic and hydrophobic monomers hydroxyethyl methacrylate (HEMA) and perfluorodecyl acrylate (PFA), respectively. Commercial RO membranes were coated with HEMA-PFA copolymer film. Long and short term biofouling studies with coated and uncoated membranes and feed spacer were performed using membrane fouling simulators (MFSs) operated in parallel, fed with water containing nutrients. For the long-term studies pressure drop development in time was monitored and after eight days the MFSs were opened and the accumulated biofilm on the membrane and spacer sheets was quantified and characterized. The presence of the membrane coating was determined using X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR). Results showed that the amphiphilic coating (i) delayed biofouling (a lower pressure drop increase by a factor of 3 and a lower accumulated active biomass amount by a factor of 6), (ii) influenced the biofilm composition (23% lower polysaccharides and 132% higher protein content) and (iii) was still completely present on the membrane at the end of the biofouling study, showing that the coating was strongly attached to the membrane surface. Using coated membranes and feed spacers in combination with advanced cleaning strategies may be a suitable way to control biofouling.

  19. Coating of reverse osmosis membranes with amphiphilic copolymers for biofouling control

    KAUST Repository

    Bucs, Szilard; Valladares Linares, Rodrigo; Siddiqui, Amber; Matin, Asif; Khan, Zafarullah; van Loosdrecht, Mark C.M.; Yang, Rong; Wang, Minghui; Gleason, Karen K.; Kruithof, Joop C.; Vrouwenvelder, Johannes S.

    2017-01-01

    Surface coating of membranes may be a promising option to control biofilm development and biofouling impact on membrane performance of spiral-wound reverse osmosis (RO) systems. The objective of this study was to investigate the impact of an amphiphilic copolymer coating on biofilm formation and biofouling control. The coating was composed of both hydrophilic and hydrophobic monomers hydroxyethyl methacrylate (HEMA) and perfluorodecyl acrylate (PFA), respectively. Commercial RO membranes were coated with HEMA-PFA copolymer film. Long and short term biofouling studies with coated and uncoated membranes and feed spacer were performed using membrane fouling simulators (MFSs) operated in parallel, fed with water containing nutrients. For the long-term studies pressure drop development in time was monitored and after eight days the MFSs were opened and the accumulated biofilm on the membrane and spacer sheets was quantified and characterized. The presence of the membrane coating was determined using X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR). Results showed that the amphiphilic coating (i) delayed biofouling (a lower pressure drop increase by a factor of 3 and a lower accumulated active biomass amount by a factor of 6), (ii) influenced the biofilm composition (23% lower polysaccharides and 132% higher protein content) and (iii) was still completely present on the membrane at the end of the biofouling study, showing that the coating was strongly attached to the membrane surface. Using coated membranes and feed spacers in combination with advanced cleaning strategies may be a suitable way to control biofouling.

  20. DSC and EPR investigations on effects of cholesterol component on molecular interactions between paclitaxel and phospholipid within lipid bilayer membrane.

    Science.gov (United States)

    Zhao, Lingyun; Feng, Si-Shen; Kocherginsky, Nikolai; Kostetski, Iouri

    2007-06-29

    Differential scanning calorimetry (DSC) and electron paramagnetic resonance spectroscopy (EPR) were applied to investigate effects of cholesterol component on molecular interactions between paclitaxel, which is one of the best antineoplastic agents found from nature, and dipalmitoylphosphatidylcholine (DPPC) within lipid bilayer vesicles (liposomes), which could also be used as a model cell membrane. DSC analysis showed that incorporation of paclitaxel into the DPPC bilayer causes a reduction in the cooperativity of bilayer phase transition, leading to a looser and more flexible bilayer structure. Including cholesterol component in the DPPC/paclitaxel mixed bilayer can facilitate the molecular interaction between paclitaxel and lipid and make the tertiary system more stable. EPR analysis demonstrated that both of paclitaxel and cholesterol have fluidization effect on the DPPC bilayer membranes although cholesterol has more significant effect than paclitaxel does. The reduction kinetics of nitroxides by ascorbic acid showed that paclitaxel can inhibit the reaction by blocking the diffusion of either the ascorbic acid or nitroxide molecules since the reaction is tested to be a first order one. Cholesterol can remarkably increase the reduction reaction speed. This research may provide useful information for optimizing liposomal formulation of the drug as well as for understanding the pharmacology of paclitaxel.

  1. Antineoplastic Effect of Decoy Oligonucleotide Derived from MGMT Enhancer

    Science.gov (United States)

    Refael, Miri; Zrihan, Daniel; Siegal, Tali; Lavon, Iris

    2014-01-01

    Silencing of O(6)-methylguanine-DNA-methyltransferase (MGMT) in tumors, mainly through promoter methylation, correlates with a better therapeutic response and with increased survival. Therefore, it is conceivable to consider MGMT as a potential therapeutic target for the treatment of cancers. Our previous results demonstrated the pivotal role of NF-kappaB in MGMT expression, mediated mainly through p65/NF-kappaB homodimers. Here we show that the non-canonical NF-KappaB motif (MGMT-kappaB1) within MGMT enhancer is probably the major inducer of MGMT expression following NF-kappaB activation. Thus, in an attempt to attenuate the transcription activity of MGMT in tumors we designed locked nucleic acids (LNA) modified decoy oligonucleotides corresponding to the specific sequence of MGMT-kappaB1 (MGMT-kB1-LODN). Following confirmation of the ability of MGMT-kB1-LODN to interfere with the binding of p65/NF-kappaB to the NF-KappaB motif within MGMT enhancer, the efficacy of the decoy was studied in-vitro and in-vivo. The results of these experiments show that the decoy MGMT-kB1-LODN have a substantial antineoplastic effect when used either in combination with temozolomide or as monotherapy. Our results suggest that MGMT-kB1-LODN may provide a novel strategy for cancer therapy. PMID:25460932

  2. Antineoplastic effect of decoy oligonucleotide derived from MGMT enhancer.

    Directory of Open Access Journals (Sweden)

    Tamar Canello

    Full Text Available Silencing of O(6-methylguanine-DNA-methyltransferase (MGMT in tumors, mainly through promoter methylation, correlates with a better therapeutic response and with increased survival. Therefore, it is conceivable to consider MGMT as a potential therapeutic target for the treatment of cancers. Our previous results demonstrated the pivotal role of NF-kappaB in MGMT expression, mediated mainly through p65/NF-kappaB homodimers. Here we show that the non-canonical NF-KappaB motif (MGMT-kappaB1 within MGMT enhancer is probably the major inducer of MGMT expression following NF-kappaB activation. Thus, in an attempt to attenuate the transcription activity of MGMT in tumors we designed locked nucleic acids (LNA modified decoy oligonucleotides corresponding to the specific sequence of MGMT-kappaB1 (MGMT-kB1-LODN. Following confirmation of the ability of MGMT-kB1-LODN to interfere with the binding of p65/NF-kappaB to the NF-KappaB motif within MGMT enhancer, the efficacy of the decoy was studied in-vitro and in-vivo. The results of these experiments show that the decoy MGMT-kB1-LODN have a substantial antineoplastic effect when used either in combination with temozolomide or as monotherapy. Our results suggest that MGMT-kB1-LODN may provide a novel strategy for cancer therapy.

  3. An organosilane-directed growth-induced etching strategy for preparing hollow/yolk–shell mesoporous organosilica nanospheres with perpendicular mesochannels and amphiphilic frameworks

    KAUST Repository

    Zou, Houbing

    2014-06-27

    We have developed an organosilane-directed growth-induced etching strategy to prepare hollow periodic mesoporous organosilica (PMO) nanospheres with perpendicular mesoporous channels and a clear hollow interior as well as an amphiphilic framework. This facile strategy is simple, efficient, and highly controllable. Silica nanospheres were utilized as hard templates to obtain hollow PMO nanospheres through a one-step route, with the structure parameter highly controlled by adjusting the synthesis conditions. Different organosilanes were used to obtain bridged hollow PMO nanospheres of different organic groups and showed different directed capacities. The integrity of the bridged organic group was confirmed by Fourier-transform infrared (FT-IR) spectroscopy and solid-state 13C nuclear magnetic resonance (NMR) spectroscopy. Transmission electron microscopy (TEM) observations showed that the growth of the PMO shell and the dissolution of the silica nanosphere core occurred simultaneously for each nanosphere, while 29Si NMR spectra revealed that the dissolved silica species from the silica nanospheres transformed into PMO shells by co-condensation with hydrolyzed organosilane oligomers. As a result, the obtained hollow nanospheres were amphiphilic, which can even be used as a particle emulsifier for O-W or W-O emulsion in various systems. These materials can also be served as an efficient sorbent for removal of hydrophobic contaminants in water. Using the proposed formation mechanism, this strategy can be extended to transform silica-coated composite materials into yolk-shell structures with a functional interior core and a perpendicular mesoporous amphiphilic shell. As a nanoreactor, the -Ph- bridged amphiphilic shell showed a faster diffusion rate for organic reactants in water than the hydrophilic silica shell, and thus better catalytic activity for reduction of 4-nitrophenol. This journal is © the Partner Organisations 2014.

  4. Ion-specific weak adsorption of salts and water/octanol transfer free energy of a model amphiphilic hexapeptide.

    Science.gov (United States)

    Déjugnat, Christophe; Dufrêche, Jean-François; Zemb, Thomas

    2011-04-21

    An amphiphilic hexapeptide has been used as a model to quantify how specific ion effects induced by addition of four salts tune the hydrophilic/hydrophobic balance and induce temperature-dependant coacervate formation from aqueous solution. The hexapeptide chosen is present as a dimer with low transfer energy from water to octanol. Taking sodium chloride as the reference state in the Hofmeister scale, we identify water activity effects and therefore measure the free energy of transfer from water to octanol and separately the free energy associated to the adsorption of chaotropic ions or the desorption of kosmotropic ions for the same amphiphilic peptide. These effects have the same order of magnitude: therefore, both energies of solvation as well as transfer into octanol strongly depend on the nature of the electrolytes used to formulate any buffer. Model peptides could be used on separation processes based on criteria linked to "Hofmeister" but different from volume and valency.

  5. Vortex-Induced Alignment of a Water Soluble Supramolecular Nanofiber Composed of an Amphiphilic Dendrimer

    Directory of Open Access Journals (Sweden)

    Akihiko Tsuda

    2013-06-01

    Full Text Available We have synthesized a novel amphiphilic naphthalene imide bearing a cationic dendrimer wedge (NID. NID molecules in water self-assemble to form a two-dimensional ribbon, which further coils to give a linear supramolecular nanofiber. The sample solution showed linear dichroism (LD upon stirring of the solution, where NID nanofibers dominantly align at the center of vortex by hydrodynamic interaction with the downward torsional flows.

  6. Silver baits for the "miraculous draught" of amphiphilic lanthanide helicates.

    Science.gov (United States)

    Terazzi, Emmanuel; Guénée, Laure; Varin, Johan; Bocquet, Bernard; Lemonnier, Jean-François; Emery, Daniel; Mareda, Jiri; Piguet, Claude

    2011-01-03

    The axial connection of flexible thioalkyls chains of variable length (n=1-12) within the segmental bis-tridentate 2-benzimidazole-8-hydroxyquinoline ligands [L12(Cn) -2 H](2-) provides amphiphilic receptors designed for the synthesis of neutral dinuclear lanthanides helicates. However, the stoichiometric mixing of metals and ligands in basic media only yields intricate mixtures of poorly soluble aggregates. The addition of Ag(I) in solution restores classical helicate architectures for n=3, with the quantitative formation of the discrete D(3) -symmetrical [Ln(2) Ag2(L12(C3) -2 H)(3) ](2+) complexes at millimolar concentration (Ln=La, Eu, Lu). The X-ray crystal structure supports the formation of [La(2) Ag(2) (L12(C3) -2 H)(3) ][OTf](2) , which exists in the solid state as infinite linear polymers bridged by S-Ag-S bonds. In contrast, molecular dynamics (MD) simulations in the gas phase and in solution confirm the experimental diffusion measurements, which imply the formation of discrete molecular entities in these media, in which the sulfur atoms of each lipophilic ligand are rapidly exchanged within the Ag(I) coordination sphere. Turned as a predictive tool, MD suggests that this Ag(I) templating effect is efficient only for n=1-3, while for n>3 very loose interactions occur between Ag(I) and the thioalkyl residues. The subsequent experimental demonstration that only 25 % of the total ligand speciation contributes to the formation of [Ln(2) Ag(2) (L12(C12) -2 H)(3) ](2+) in solution puts the bases for a rational approach for the design of amphiphilic helical complexes with predetermined molecular interfaces. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. [Blending powdered antineoplastic medicine in disposable ointment container].

    Science.gov (United States)

    Miyazaki, Yasunori; Uchino, Tomonobu; Kagawa, Yoshiyuki

    2014-01-01

    On dispensing powdered antineoplastic medicines, it is important to prevent cross-contamination and environmental exposure. Recently, we developed a method for blending powdered medicine in a disposable ointment container using a planetary centrifugal mixer. The disposable container prevents cross-contamination. In addition, environmental exposure associated with washing the apparatus does not arise because no blending blade is used. In this study, we aimed to confirm the uniformity of the mixture and weight loss of medicine in the blending procedure. We blended colored lactose powder with Leukerin(®) or Mablin(®) powders using the new method and the ordinary pestle and mortar method. Then, the blending state was monitored using image analysis. Blending variables, such as the blending ratio (1:9-9:1), container size (35-125 mL), and charging rate (20-50%) in the container were also investigated under the operational conditions of 500 rpm and 50 s. At a 20% charging rate in a 35 mL container, the blending precision of the mixtures was not influenced by the blending ratio, and was less than 6.08%, indicating homogeneity. With an increase in the charging rate, however, the blending precision decreased. The possible amount of both mixtures rose to about 17 g with a 20% charging rate in a 125 mL container. Furthermore, weight loss of medicines with this method was smaller than that with the pestle and mortar method, suggesting that this method is safer for pharmacists. In conclusion, we have established a precise and safe method for blending powdered medicines in pharmacies.

  8. Preparation of pH-sensitive amphiphilic block star polymers, their self-assembling characteristics and release behavior on encapsulated molecules

    KAUST Repository

    Song, Xiaowan; Cao, Ming; Chen, Peng; Xia, Ru; Zheng, Zhengzhi; Miao, Jibin; Yang, Bin; Su, Lifen; Qian, Jiasheng; Feng, Xiaoshuang

    2016-01-01

    Poly(ethylene glycol) (PEG), a polymer with excellent biocompatibility, was widely used to form nanoparticles for drug delivery applications. In this paper, based on PEG, a series of pH-sensitive amphiphilic block star polymers of poly

  9. Macroscopic alignment of graphene stacks by Langmuir-Blodgett deposition of amphiphilic hexabenzocoronenes

    DEFF Research Database (Denmark)

    Laursen, B.W.; Nørgaard, K.; Reitzel, N.

    2004-01-01

    ). Grazing-incidence X-ray diffraction (GIXD) and X-ray reflectivity, both utilizing synchrotron radiation, show that these amphiphilic HBCs form well-defined Langmuir monolayers at the air-water interface, with pi-stacked columnar structure where the HBC cores are rotated around the surface normal...... and tilted relative to the water surface. The intercolumnar distance is 20 A. The HBCs are confined to a layer lying on top of the layer of polar groups that are in contact with the water subphase. Efficient transfer of the monolayer of the anthraquinone-substituted HBC derivative to hydrophobic quartz...

  10. Probing the amphiphile micellar to hexagonal phase transition using Positron Annihilation Lifetime Spectroscopy.

    Science.gov (United States)

    Dong, Aurelia W; Fong, Celesta; Hill, Anita J; Boyd, Ben J; Drummond, Calum J

    2013-07-15

    Positron Annihilation Lifetime Spectroscopy (PALS) has been utilised only sparingly for structural characterisation in self assembled materials. Inconsistencies in approaches to experimental configuration and data analysis between studies has complicated comparisons between studies, meaning that the technique has not provided a cohesive data set across the study of different self assembled systems that advance the technique towards an important tool in soft matter research. In the current work a systematic study was conducted using ionic and non-ionic micellar systems with increasing surfactant concentration to probe positron behaviour on changes between micellar phase structures, and data analysed using contemporary approaches to fit four component spectra. A characteristic orthopositronium lifetime (in the organic regions) of 3.5±0.2 ns was obtained for the hexagonal phase for surfactants with C12 alkyl chains. Chemical quenching of the positron species was also observed for systems with ionic amphiphiles. The application of PALS has also highlighted an inconsistency in the published phase diagram for the octa(ethylene oxide) monododecyl ether (C12EO8) system. These results provide new insight into how the physical properties of micellar systems can be related to PALS parameters and means that the PALS technique can be applied to other more complex self-assembled amphiphile systems. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Water around fullerene shape amphiphiles: A molecular dynamics simulation study of hydrophobic hydration

    Energy Technology Data Exchange (ETDEWEB)

    Varanasi, S. R., E-mail: s.raovaranasi@uq.edu.au, E-mail: guskova@ipfdd.de; John, A. [Institut Theorie der Polymere, Leibniz-Institut für Polymerforschung Dresden e.V., Hohe Straße 6, Dresden D-01069 (Germany); Guskova, O. A., E-mail: s.raovaranasi@uq.edu.au, E-mail: guskova@ipfdd.de [Institut Theorie der Polymere, Leibniz-Institut für Polymerforschung Dresden e.V., Hohe Straße 6, Dresden D-01069 (Germany); Dresden Center for Computational Materials Science (DCMS), Technische Universität Dresden, Dresden D-01069 (Germany); Sommer, J.-U. [Institut Theorie der Polymere, Leibniz-Institut für Polymerforschung Dresden e.V., Hohe Straße 6, Dresden D-01069 (Germany); Dresden Center for Computational Materials Science (DCMS), Technische Universität Dresden, Dresden D-01069 (Germany); Institut für Theoretische Physik, Technische Universität Dresden, Zellescher Weg 17, Dresden D-01069 (Germany)

    2015-06-14

    Fullerene C{sub 60} sub-colloidal particle with diameter ∼1 nm represents a boundary case between small and large hydrophobic solutes on the length scale of hydrophobic hydration. In the present paper, a molecular dynamics simulation is performed to investigate this complex phenomenon for bare C{sub 60} fullerene and its amphiphilic/charged derivatives, so called shape amphiphiles. Since most of the unique properties of water originate from the pattern of hydrogen bond network and its dynamics, spatial, and orientational aspects of water in solvation shells around the solute surface having hydrophilic and hydrophobic regions are analyzed. Dynamical properties such as translational-rotational mobility, reorientational correlation and occupation time correlation functions of water molecules, and diffusion coefficients are also calculated. Slower dynamics of solvent molecules—water retardation—in the vicinity of the solutes is observed. Both the topological properties of hydrogen bond pattern and the “dangling” –OH groups that represent surface defects in water network are monitored. The fraction of such defect structures is increased near the hydrophobic cap of fullerenes. Some “dry” regions of C{sub 60} are observed which can be considered as signatures of surface dewetting. In an effort to provide molecular level insight into the thermodynamics of hydration, the free energy of solvation is determined for a family of fullerene particles using thermodynamic integration technique.

  12. Water around fullerene shape amphiphiles: A molecular dynamics simulation study of hydrophobic hydration

    International Nuclear Information System (INIS)

    Varanasi, S. R.; John, A.; Guskova, O. A.; Sommer, J.-U.

    2015-01-01

    Fullerene C 60 sub-colloidal particle with diameter ∼1 nm represents a boundary case between small and large hydrophobic solutes on the length scale of hydrophobic hydration. In the present paper, a molecular dynamics simulation is performed to investigate this complex phenomenon for bare C 60 fullerene and its amphiphilic/charged derivatives, so called shape amphiphiles. Since most of the unique properties of water originate from the pattern of hydrogen bond network and its dynamics, spatial, and orientational aspects of water in solvation shells around the solute surface having hydrophilic and hydrophobic regions are analyzed. Dynamical properties such as translational-rotational mobility, reorientational correlation and occupation time correlation functions of water molecules, and diffusion coefficients are also calculated. Slower dynamics of solvent molecules—water retardation—in the vicinity of the solutes is observed. Both the topological properties of hydrogen bond pattern and the “dangling” –OH groups that represent surface defects in water network are monitored. The fraction of such defect structures is increased near the hydrophobic cap of fullerenes. Some “dry” regions of C 60 are observed which can be considered as signatures of surface dewetting. In an effort to provide molecular level insight into the thermodynamics of hydration, the free energy of solvation is determined for a family of fullerene particles using thermodynamic integration technique

  13. Synthesis and properties of amphiphilic hyperbranched polyethers as pigment dispersant

    Science.gov (United States)

    Xu, Q.; Zhou, Y. J.; Long, S. J.; Liu, Y. G.; Li, J. H.

    2018-01-01

    Hyperbranched polymers possess prominent properties such as low viscosity, good solubility, high rheological property, environmental non-toxic, and so on, which have potential applications in coatings. In this study, the amphiphilic hyperbranched polyethers (AHPs) consisting of hydrophobic hyperbranched polyethers core and hydrophilic poly (ethylene glycol) arms with different degree of branching (DB) under various reaction temperatures was prepared by the cation ring-opening polymerization. Their structures were characterized by IR, 13CNMR and GPC. Their dispersion properties for pigment particles were investigated. The AHP47 with 0.47 DB was found to have good dispersion properties for Yellow HGR. This work would provide experimental data and theoretical foundation for the application of hyperbranched polyethers in environmental protection coating.

  14. Using amphiphilic nanostructures to enable long-range ensemble coalescence and surface rejuvenation in dropwise condensation.

    Science.gov (United States)

    Anderson, David M; Gupta, Maneesh K; Voevodin, Andrey A; Hunter, Chad N; Putnam, Shawn A; Tsukruk, Vladimir V; Fedorov, Andrei G

    2012-04-24

    Controlling coalescence events in a heterogeneous ensemble of condensing droplets on a surface is an outstanding fundamental challenge in surface and interfacial sciences, with a broad practical importance in applications ranging from thermal management of high-performance electronic devices to moisture management in high-humidity environments. Nature-inspired superhydrophobic surfaces have been actively explored to enhance heat and mass transfer rates by achieving favorable dynamics during dropwise condensation; however, the effectiveness of such chemically homogeneous surfaces has been limited because condensing droplets tend to form as pinned Wenzel drops rather than mobile Cassie ones. Here, we introduce an amphiphilic nanostructured surface, consisting of a hydrophilic base with hydrophobic tips, which promotes the periodic regeneration of nucleation sites for small droplets, thus rendering the surface self-rejuvenating. This unique amphiphilic nanointerface generates an arrangement of condensed Wenzel droplets that are fluidically linked by a wetted sublayer, promoting previously unobserved coalescence events where numerous droplets simultaneously merge, without direct contact. Such ensemble coalescences rapidly create fresh nucleation sites, thereby shifting the overall population toward smaller droplets and enhancing the rates of mass and heat transfer during condensation.

  15. Superior Antifouling Performance of a Zwitterionic Peptide Compared to an Amphiphilic, Non-Ionic Peptide.

    Science.gov (United States)

    Ye, Huijun; Wang, Libing; Huang, Renliang; Su, Rongxin; Liu, Boshi; Qi, Wei; He, Zhimin

    2015-10-14

    The aim of this study was to explore the influence of amphiphilic and zwitterionic structures on the resistance of protein adsorption to peptide self-assembled monolayers (SAMs) and gain insight into the associated antifouling mechanism. Two kinds of cysteine-terminated heptapeptides were studied. One peptide had alternating hydrophobic and hydrophilic residues with an amphiphilic sequence of CYSYSYS. The other peptide (CRERERE) was zwitterionic. Both peptides were covalently attached onto gold substrates via gold-thiol bond formation. Surface plasmon resonance analysis results showed that both peptide SAMs had ultralow or low protein adsorption amounts of 1.97-11.78 ng/cm2 in the presence of single proteins. The zwitterionic peptide showed relatively higher antifouling ability with single proteins and natural complex protein media. We performed molecular dynamics simulations to understand their respective antifouling behaviors. The results indicated that strong surface hydration of peptide SAMs contributes to fouling resistance by impeding interactions with proteins. Compared to the CYSYSYS peptide, more water molecules were predicted to form hydrogen-bonding interactions with the zwitterionic CRERERE peptide, which is in agreement with the antifouling test results. These findings reveal a clear relation between peptide structures and resistance to protein adsorption, facilitating the development of novel peptide-containing antifouling materials.

  16. Fliposomes: pH-triggered conformational flip of new trans-2-aminocyclohexanol-based amphiphiles causes instant cargo release in liposomes.

    Science.gov (United States)

    Liu, Xin; Zheng, Yu; Samoshina, Nataliya M; Franz, Andreas H; Guo, Xin; Samoshin, Vyacheslav V

    2012-12-01

    A new type of pH-sensitive liposomes (fliposomes) was designed based on the amphiphiles that are able to perform a pH-triggered conformational flip (flipids). This flip disrupts the liposome membrane and causes rapid release of the liposome cargo, specifically in response to lowered pH. The flipids (1) and (2) are equipped with a trans-2-aminocyclohexanol conformational switch. pH-sensitive fliposomes containing one or both of these flipids, as well as POPC and PEG ceramide, were constructed and characterized. These compositions were stable at 4°C and pH 7.4 for several months. Fliposomes loaded with ANTS/DPX performed an unusually quick content release within a few seconds at pH below 8.5 (in case of 2) and 6.0 (in case of 1). This difference in pH sensitivity demonstrates a potential for the custom design of flipids by variation of the amino group to target areas with specific pH values. The pH titration curves for the fliposome leakage parallel the curves for the acid-induced conformational flip of 1 and 2 studied by ¹H NMR. A plausible mechanism of pH sensitivity starts with an acid-triggered conformational flip of 1 or 2, which changes the molecular size and shape, shortens the lipid tails, and perturbs the liposome membrane, resulting in the content leakage.

  17. Amphiphilic polymer promoted assembly of macroporous graphene/SnO2 frameworks with tunable porosity for high-performance lithium storage.

    Science.gov (United States)

    Huang, Yanshan; Wu, Dongqing; Wang, Jinzuan; Han, Sheng; Lv, Lu; Zhang, Fan; Feng, Xinliang

    2014-06-12

    3D macroporous graphene/SnO2 frameworks (MGTFs) are fabricated by amphiphilic polymer-promoted assembly method, which exhibit controllable macroporous structure and outstanding lithium storage performance. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. An Experimental and Molecular Dynamics Investigation into the Amphiphilic Nature of Sulforhodamine B

    OpenAIRE

    Polat, Baris E.; Lin, Shangchao; Mendenhall, Jonathan D.; VanVeller, Brett; Langer, Robert; Blankschtein, Daniel

    2011-01-01

    Sulforhodamine B (SRB), a common fluorescent dye, is often considered to be a purely hydrophilic molecule, having no impact on bulk or interfacial properties of aqueous solutions. This assumption is due to the high water solubility of SRB relative to most fluorescent probes. However, in the present study, we demonstrate that SRB is in fact an amphiphile, with the ability to adsorb at an air/water interface and to incorporate into sodium dodecyl sulfate (SDS) micelles. In fact, SRB reduces the...

  19. Adamantane-based amphiphiles (ADAs) for membrane protein study: importance of a detergent hydrophobic group in membrane protein solubilisation.

    Science.gov (United States)

    Chae, Pil Seok; Bae, Hyoung Eun; Das, Manabendra

    2014-10-21

    We prepared adamantane-containing amphiphiles and evaluated them using a large membrane protein complex in terms of protein solubilisation and stabilization efficacy. These agents were superior to conventional detergents, especially in terms of the membrane protein solubilisation efficiency, implying a new detergent structure-property relationship.

  20. BRCAA1 antibody- and Her2 antibody-conjugated amphiphilic polymer engineered CdSe/ZnS quantum dots for targeted imaging of gastric cancer

    Science.gov (United States)

    Li, Chao; Ji, Yang; Wang, Can; Liang, Shujing; Pan, Fei; Zhang, Chunlei; Chen, Feng; Fu, Hualin; Wang, Kan; Cui, Daxiang

    2014-05-01

    Successful development of safe and highly effective nanoprobes for targeted imaging of in vivo early gastric cancer is a great challenge. Herein, we choose the CdSe/ZnS (core-shell) quantum dots (QDs) as prototypical materials, synthesized one kind of a new amphiphilic polymer including dentate-like alkyl chains and multiple carboxyl groups, and then used the prepared amphiphilic polymer to modify QDs. The resultant amphiphilic polymer engineered QDs (PQDs) were conjugated with BRCAA1 and Her2 monoclonal antibody, and prepared BRCAA1 antibody- and Her2 antibody-conjugated QDs were used for in vitro MGC803 cell labeling and in vivo targeted imaging of gastric cancer cells. Results showed that the PQDs exhibited good water solubility, strong photoluminescence (PL) intensity, and good biocompatibility. BRCAA1 antibody- and Her2 antibody-conjugated QD nanoprobes successfully realized targeted imaging of in vivo gastric cancer MGC803 cells. In conclusion, BRCAA1 antibody- and Her2 antibody-conjugated PQDs have great potential in applications such as single cell labeling and in vivo tracking, and targeted imaging and therapeutic effects' evaluation of in vivo early gastric cancer cells in the near future.

  1. Supramolecular ribbons from amphiphilic trisamides self-assembly.

    Science.gov (United States)

    García, Fátima; Buendía, Julia; Sánchez, Luis

    2011-08-05

    Two amphiphilic C(3)-symmetric OPE-based trisamides have been synthesized and their self-assembling features investigated in solution and on surface. Variable-temperature UV-vis experiments demonstrate the cooperative supramolecular polymerization of these trisamides that self-assemble by the operation of triple C═O···H-N H-bonding arrays between the amide functional groups and π-π stacking between the aromatic units. The helical organization of the aggregates has been demonstrated by circular dichroism at a concentration as low as 1 × 10(-4) M in acetonitrile. In the reported trisamides, the large hydrophobic aromatic core acts as a solvophobic module impeding the interaction between the polar TEG chains and the amide H-bonds. This strategy makes unnecessary the separation of the amide functional groups to the polar tri(ethylene glycol) chains by paraffinic fragments. Achiral trisamide 1 self-assembles into flat ribbon-like structures that experience an amplification of chirality by the addition of a small amount of chiral 2 that generates twisted stripes.

  2. Nanoparticles based on novel amphiphilic polyaspartamide copolymers

    International Nuclear Information System (INIS)

    Craparo, Emanuela Fabiola; Teresi, Girolamo; Ognibene, Maria Chiara; Casaletto, Maria Pia; Bondi, Maria Luisa; Cavallaro, Gennara

    2010-01-01

    In this article, the synthesis of two amphiphilic polyaspartamide copolymers, useful to obtain polymeric nanoparticles without using surfactants or stabilizing agents, is described. These copolymers were obtained starting from α,β-poly-(N-2-hydroxyethyl)-dl-aspartamide (PHEA) by following a novel synthetic strategy. In particular, PHEA and its pegylated derivative (PHEA-PEG 2000 ) were functionalized with poly(lactic acid) (PLA) through 1,1'-carbonyldiimidazole (CDI) activation to obtain PHEA-PLA and PHEA-PEG 2000 -PLA graft copolymers, respectively. These copolymers were properly purified and characterized by 1 H-NMR, FT-IR, and Size Exclusion Chromatography (SEC) analyses, which confirmed that derivatization reactions occurred. Nanoparticles were obtained from PHEA-PLA and PHEA-PEG 2000 -PLA graft copolymers by using the high pressure homogenization-solvent evaporation method, avoiding the use of surfactants or stabilizing agents. Polymeric nanoparticles were characterized by dimensional analysis, before and after freeze-drying process, and Scanning Electron Microscopy (SEM). Zeta potential measurements and X-ray Photoelectron Spectroscopy (XPS) analysis demonstrated the presence of PEG and/or PHEA onto the PHEA-PEG 2000 -PLA and PHEA-PLA nanoparticle surface, respectively.

  3. Polyene-lipids: a new tool to image lipids

    DEFF Research Database (Denmark)

    Kuerschner, Lars; Ejsing, Christer S.; Ekroos, Kim

    2005-01-01

    conjugated double bonds as a new type of lipid tag. Polyene-lipids exhibit a unique structural similarity to natural lipids, which results in minimal effects on the lipid properties. Analyzing membrane phase partitioning, an important biophysical and biological property of lipids, we demonstrated......Microscopy of lipids in living cells is currently hampered by a lack of adequate fluorescent tags. The most frequently used tags, NBD and BODIPY, strongly influence the properties of lipids, yielding analogs with quite different characteristics. Here, we introduce polyene-lipids containing five...... the superiority of polyene-lipids to both NBD- and BODIPY-tagged lipids. Cells readily take up various polyene-lipid precursors and generate the expected end products with no apparent disturbance by the tag. Applying two-photon excitation microscopy, we imaged the distribution of polyene-lipids in living...

  4. Vitamin E succinate is a potent novel antineoplastic agent with high selectivity and cooperativity with tumor necrosis factor-related apoptosis-inducing ligand (Apo2 ligand) in vivo

    Czech Academy of Sciences Publication Activity Database

    Weber, T.; Lu, M.; Anděra, Ladislav; Lahm, H.; Gellert, N.; Fariss, M. W.; Kořínek, Vladimír; Sattler, W.; Ucker, D. S.; Terman, A.; Schroder, A.; Erl, W.; Brunk, U. T.; Coffey, R. J.; Weber, C.; Neuzil, J.

    2002-01-01

    Roč. 8, - (2002), s. 863-869 ISSN 1078-0432 R&D Projects: GA ČR GA312/99/0348 Institutional research plan: CEZ:AV0Z5052915 Keywords : Vitamin E, Antineoplastic Agent, Tumor Necrosis Factor Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.991, year: 2002

  5. Ion-specific weak adsorption of salts and water/octanol transfer free energy of a model amphiphilic hexa-peptide

    International Nuclear Information System (INIS)

    Dejugnat, Ch.; Dufreche, J.F.; Zemb, Th.; Dejugnat, Ch.

    2011-01-01

    An amphiphilic hexa-peptide has been used as a model to quantify how specific ion effects induced by addition of four salts tune the hydrophilic/hydrophobic balance and induce temperature-dependant coacervate formation from aqueous solution. The hexa-peptide chosen is present as a dimer with low transfer energy from water to octanol. Taking sodium chloride as the reference state in the Hofmeister scale, we identify water activity effects and therefore measure the free energy of transfer from water to octanol and separately the free energy associated to the adsorption of chaotropic ions or the desorption of kosmotropic ions for the same amphiphilic peptide. These effects have the same order of magnitude: therefore, both energies of solvation as well as transfer into octanol strongly depend on the nature of the electrolytes used to formulate any buffer. Model peptides could be used on separation processes based on criteria linked to 'Hofmeister' but different from volume and valency. (authors)

  6. Self assembly of amphiphilic C60 fullerene derivatives into nanoscale supramolecular structures

    Directory of Open Access Journals (Sweden)

    Casscells S Ward

    2007-08-01

    Full Text Available Abstract Background The amphiphilic fullerene monomer (AF-1 consists of a "buckyball" cage to which a Newkome-like dendrimer unit and five lipophilic C12 chains positioned octahedrally to the dendrimer unit are attached. In this study, we report a novel fullerene-based liposome termed 'buckysome' that is water soluble and forms stable spherical nanometer sized vesicles. Cryogenic electron microscopy (Cryo-EM, transmission electron microscopy (TEM, and dynamic light scattering (DLS studies were used to characterize the different supra-molecular structures readily formed from the fullerene monomers under varying pH, aqueous solvents, and preparative conditions. Results Electron microscopy results indicate the formation of bilayer membranes with a width of ~6.5 nm, consistent with previously reported molecular dynamics simulations. Cryo-EM indicates the formation of large (400 nm diameter multilamellar, liposome-like vesicles and unilamellar vesicles in the size range of 50–150 nm diameter. In addition, complex networks of cylindrical, tube-like aggregates with varying lengths and packing densities were observed. Under controlled experimental conditions, high concentrations of spherical vesicles could be formed. In vitro results suggest that these supra-molecular structures impose little to no toxicity. Cytotoxicity of 10–200 μM buckysomes were assessed in various cell lines. Ongoing studies are aimed at understanding cellular internalization of these nanoparticle aggregates. Conclusion In this current study, we have designed a core platform based on a novel amphiphilic fullerene nanostructure, which readily assembles into supra-molecular structures. This delivery vector might provide promising features such as ease of preparation, long-term stability and controlled release.

  7. Amphiphilic hollow porous shell encapsulated Au@Pd bimetal nanoparticles for aerobic oxidation of alcohols in water

    KAUST Repository

    Zou, Houbing

    2015-01-01

    © The Royal Society of Chemistry 2015. This work describes the design, synthesis and analysis of an amphiphilic hollow mesoporous shell encapsulating catalytically active Au@Pd bimetal nanoparticles. The particles exhibited excellent catalytic activity and stability in the aerobic oxidation of primary and secondary alcohols to their corresponding aldehydes or ketones in water when using air as an oxidizing agent under atmospheric pressure.

  8. Amphiphilic copolymers based on PEG-acrylate as surface active water viscosifiers : Towards new potential systems for enhanced oil recovery

    NARCIS (Netherlands)

    Raffa, Patrizio; Broekhuis, Antonius A.; Picchioni, Francesco

    2016-01-01

    With the purpose of investigating new potential candidates for enhanced oil recovery (EOR), amphiphilic copolymers based on Poly(ethylene glycol) methyl ether acrylate (PEGA) have been prepared by Atom Transfer Radical Polymerization (ATRP). A P(PEGA) homopolymer, a block copolymer with styrene

  9. The anti-neoplastic activity of Vandetanib against high-risk medulloblastoma variants is profoundly enhanced by additional PI3K inhibition.

    Science.gov (United States)

    Craveiro, Rogerio B; Ehrhardt, Michael; Velz, Julia; Olschewski, Martin; Goetz, Barbara; Pietsch, Torsten; Dilloo, Dagmar

    2017-07-18

    Medulloblastoma is comprised of at least four molecular subgroups with distinct clinical outcome (WHO classification 2016). SHH-TP53-mutated as well as MYC-amplified Non-WNT/Non-SHH medulloblastoma show the worst prognosis.Here we present evidence that single application of the multi-kinase inhibitor Vandetanib displays anti-neoplastic efficacy against cell lines derived from high-risk SHH-TP53-mutated and MYC-amplified Non-WNT/Non-SHH medulloblastoma. The narrow target spectrum of Vandetanib along with a favourable toxicity profile renders this drug ideal for multimodal treatment approaches. In this context our investigation documents that Vandetanib in combination with the clinically available PI3K inhibitor GDC-0941 leads to enhanced cytotoxicity against MYC-amplified and SHH-TP53-mutated medulloblastoma. In line with these findings we show for MYC-amplified medulloblastoma a profound reduction in activity of the oncogenes STAT3 and AKT. Furthermore, we document that Vandetanib and the standard chemotherapeutic Etoposide display additive anti-neoplastic efficacy in the investigated medulloblastoma cell lines that could be further enhanced by PI3K inhibition. Of note, the combination of Vandetanib, GDC-0941 and Etoposide results in MYC-amplified and SHH-TP53-mutated cell lines in complete loss of cell viability. Our findings therefore provide a rational to further evaluate Vandetanib in combination with PI3K inhibitors as well as standard chemotherapeutics in vivo for the treatment of most aggressive medulloblastoma variants.

  10. Delving into cornerstones of hypersensitivity to antineoplastic and biological agents: value of diagnostic tools prior to desensitization.

    Science.gov (United States)

    Alvarez-Cuesta, E; Madrigal-Burgaleta, R; Angel-Pereira, D; Ureña-Tavera, A; Zamora-Verduga, M; Lopez-Gonzalez, P; Berges-Gimeno, M P

    2015-07-01

    Evidence regarding drug provocation test (DPT) with antineoplastic and biological agents is scarce. Our aim was to assess the usefulness of including DPT as a paramount gold standard diagnostic tool (prior to desensitization). Prospective, observational, longitudinal study with patients who, during a 3-year period, were referred to the Desensitization Program at Ramon y Cajal University Hospital. Patients underwent a structured diagnostic protocol by means of anamnesis, skin tests (ST), risk assessment, and DPT. Oxaliplatin-specific IgE was determined in oxaliplatin-reactive patients (who underwent DPT regardless of oxaliplatin-specific IgE results). Univariate analysis and multivariate analysis were used to identify predictors of the final diagnosis among several variables. A total of 186 patients were assessed. A total of 104 (56%) patients underwent DPT. Sixty-four percent of all DPTs were negative (i.e., hypersensitivity was excluded). Sensitivity for oxaliplatin-specific IgE (0.35 UI/l cutoff point) was 34%, specificity 90.3%, negative predictive value 45.9%, positive predictive value 85%, negative likelihood ratio 0.7, and positive likelihood ratio 3.5. These are the first reported data based on more than 100 DPTs with antineoplastic and biological agents (paclitaxel, oxaliplatin, rituximab, infliximab, irinotecan, and other drugs). Implementation of DPT in diagnostic protocols helps exclude hypersensitivity (in 36% of all referred patients), and avoids unnecessary desensitizations in nonhypersensitive patients (30-56% of patients, depending on culprit-drug). Drug provocation test is vital to validate diagnostic tools; consequently, quality data are shown on oxaliplatin-specific IgE and oxaliplatin-ST in the largest series of oxaliplatin-reactive patients reported to date (74 oxaliplatin-reactive patients). Identifying phenotypes and predictors of a diagnosis of hypersensitivity may be helpful for tailored plans. © 2015 John Wiley & Sons A/S. Published by

  11. Antineoplastic Activities of MT81 and Its Structural Analogue in Ehrlich Ascites Carcinoma-Bearing Swiss Albino Mice

    Directory of Open Access Journals (Sweden)

    Sujata Maiti Choudhury

    2010-01-01

    Full Text Available Many fungal toxins exhibit in vitro and in vivo antineoplastic effects on various cancer cell types. Luteoskyrin, a hydroxyanthraquinone has been proved to be a potent inhibitor against Ehrlich ascites tumor cells. The comparative antitumor activity and antioxidant status of MT81 and its structural analogue [Acetic acid-MT81 (Aa-MT81] having polyhydroxyanthraquinone structure were assessed against Ehrlich ascites carcinoma (EAC tumor in mice. The in vitro cytotoxicity was measured by the viability of EAC cells after direct treatment of the said compounds. In in vivo study, MT81 and its structural analogue were administered (i.p. at the two different doses (5, 7 mg MT81; 8.93, 11.48 mg Aa-MT81/kg body weight for 7 days after 24 hrs. of tumor inoculation. The activities were assessed using mean survival time (MST, increased life span (ILS, tumor volume, viable tumor cell count, peritoneal cell count, protein percentage and hematological parameters. Antioxidant status was determined by malondialdehyde (MDA and reduced glutathione (GSH content, and by the activity of superoxide dismutase (SOD and catalase (CA T. MT81 and its structural analogues increased the mean survival time, normal peritoneal cell count. They decreased the tumor volume, viable tumor cell count, hemoglobin percentage and packed cell volume. Differential counts of WBC, total counts of RBC & WBC that altered by EAC inoculation, were restored in a dose-dependent manner. Increased MDA and decreased GSH content and reduced activity of SOD, and catalase in EAC bearing mice were returned towards normal after the treatment of MT81 and its structural analogue. Being less toxic than parent toxin MT81, the structural analogue showed more prominent antineoplastic activities against EAC cells compared to MT81. At the same time, both compounds exhibit to some extent antioxidant potential for the EAC-bearing mice.

  12. Recovery and redispersion of gold nanoparticles using the self-assembly of a pH sensitive zwitterionic amphiphile.

    Science.gov (United States)

    Morita-Imura, Clara; Imura, Yoshiro; Kawai, Takeshi; Shindo, Hitoshi

    2014-11-04

    The pH-responsive self-assembly of zwitterionic amphiphile C16CA was expanded to the recovery of gold (Au) nanoparticles for environmentally friendly chemistry applications. Multilayered lamellae at pH ∼ 4 were successfully incorporated into nanoparticles by dispersion. Redispersion of nanoparticles was achieved under basic conditions by the transition of self-assembly.

  13. Tipping the Scale from Disorder to Alpha-helix: Folding of Amphiphilic Peptides in the Presence of Macroscopic and Molecular Interfaces.

    Science.gov (United States)

    Dalgicdir, Cahit; Globisch, Christoph; Peter, Christine; Sayar, Mehmet

    2015-08-01

    Secondary amphiphilicity is inherent to the secondary structural elements of proteins. By forming energetically favorable contacts with each other these amphiphilic building blocks give rise to the formation of a tertiary structure. Small proteins and peptides, on the other hand, are usually too short to form multiple structural elements and cannot stabilize them internally. Therefore, these molecules are often found to be structurally ambiguous up to the point of a large degree of intrinsic disorder in solution. Consequently, their conformational preference is particularly susceptible to environmental conditions such as pH, salts, or presence of interfaces. In this study we use molecular dynamics simulations to analyze the conformational behavior of two synthetic peptides, LKKLLKLLKKLLKL (LK) and EAALAEALAEALAE (EALA), with built-in secondary amphiphilicity upon forming an alpha-helix. We use these model peptides to systematically study their aggregation and the influence of macroscopic and molecular interfaces on their conformational preferences. We show that the peptides are neither random coils in bulk water nor fully formed alpha helices, but adopt multiple conformations and secondary structure elements with short lifetimes. These provide a basis for conformation-selection and population-shift upon environmental changes. Differences in these peptides' response to macroscopic and molecular interfaces (presented by an aggregation partner) can be linked to their inherent alpha-helical tendencies in bulk water. We find that the peptides' aggregation behavior is also strongly affected by presence or absence of an interface, and rather subtly depends on their surface charge and hydrophobicity.

  14. Genetically encoded lipid-polypeptide hybrid biomaterials that exhibit temperature-triggered hierarchical self-assembly

    Science.gov (United States)

    Mozhdehi, Davoud; Luginbuhl, Kelli M.; Simon, Joseph R.; Dzuricky, Michael; Berger, Rüdiger; Varol, H. Samet; Huang, Fred C.; Buehne, Kristen L.; Mayne, Nicholas R.; Weitzhandler, Isaac; Bonn, Mischa; Parekh, Sapun H.; Chilkoti, Ashutosh

    2018-05-01

    Post-translational modification of proteins is a strategy widely used in biological systems. It expands the diversity of the proteome and allows for tailoring of both the function and localization of proteins within cells as well as the material properties of structural proteins and matrices. Despite their ubiquity in biology, with a few exceptions, the potential of post-translational modifications in biomaterials synthesis has remained largely untapped. As a proof of concept to demonstrate the feasibility of creating a genetically encoded biohybrid material through post-translational modification, we report here the generation of a family of three stimulus-responsive hybrid materials—fatty-acid-modified elastin-like polypeptides—using a one-pot recombinant expression and post-translational lipidation methodology. These hybrid biomaterials contain an amphiphilic domain, composed of a β-sheet-forming peptide that is post-translationally functionalized with a C14 alkyl chain, fused to a thermally responsive elastin-like polypeptide. They exhibit temperature-triggered hierarchical self-assembly across multiple length scales with varied structure and material properties that can be controlled at the sequence level.

  15. Microspheres for protein delivery prepared from amphiphilic multiblock copolymers. 1. influence of preparation techniques on particle characteristics and protein delivery

    NARCIS (Netherlands)

    Bezemer, J.M.; Radersma, R.; Grijpma, Dirk W.; Dijkstra, Pieter J.; van Blitterswijk, Clemens; Feijen, Jan

    2000-01-01

    The entrapment of lysozyme in amphiphilic multiblock copolymer microspheres by emulsification and subsequent solvent removal processes was studied. The copolymers are composed of hydrophilic poly(ethylene glycol) (PEG) blocks and hydrophobic poly(butylene terephthalate) (PBT) blocks. Direct solvent

  16. Catanionic mixtures forming gemini-like amphiphiles.

    Science.gov (United States)

    Sakai, Hideki; Okabe, Yuji; Tsuchiya, Koji; Sakai, Kenichi; Abe, Masahiko

    2011-01-01

    The properties of aqueous mixtures of cationic species with alkyl dicarboxylic acid compounds have been studied. The cationic compounds used in this study were tertiary amine-type N-methyl-N-(2,3-dioxypropyl)hexadecylamine (C16amine) and quaternary ammonium-type N,N-dimethyl-N-(2,3-dioxypropyl)hexadecylammonium chloride (C16Q). The alkyl dicarboxylic acid compounds used were HOOC(CH(2))(10)COOH (C12H) and its sodium salt (C12Na). Three aqueous mixtures were examined in this study: (System I) C16amine + C12H, (System II) C16Q + C12Na, and (System III) C16Q + C12H. The solution pH was set at 12 for System III. The combination of (1)H-NMR and mass spectroscopy data has suggested that a stoichiometric complex is formed in the aqueous solutions at a mole fraction of C12H (or C12Na) = 0.33. Here, the C12H (or C12Na) molecule added to the system bridges two cationic molecules, like a spacer of gemini surfactants. In fact, the static surface tensiometry has demonstrated that the stoichiometric complex behaves as gemini-like amphiphiles in aqueous solutions. Our current study offers a possible way for easily preparing gemini surfactant systems.

  17. The Antineoplastic Effect of Nitric Oxide-Donating Acetylsalicylic Acid (NO-ASA) in Chronic Lymphocytic Leukemia (CLL) Cells is Highly Dependent on its Positional Isomerism.

    Science.gov (United States)

    Gehrke, Iris; Razavi, Regina; Poll-Wolbeck, Simon Jonas; Berkessel, Albrecht; Hallek, Michael; Kreuzer, Karl-Anton

    2011-10-01

    Chronic Lymphocytic Leukemia (CLL) is not curable in patients that are not eligible for allogeneic stem cell transplantation. Therefore, new treatment options are highly desirable. Chemically modified nonsteroidal anti-inflammatory drugs (NSAIDs), such as nitric-oxide-donating acetylsalicylic acid (NO-ASA), have been described to possess antineoplastic capacity. Recently, we could demonstrate a potent apoptosis induction in primary CLL cells in vitro and tumor growth inhibition by para-NO-ASA in a xenograft mouse model. However, little is known about the impact of positional isomerism of NO-ASA on its antineoplastic capacity in CLL. Primary CLL cells were treated with the meta-or para-isomer of NO-ASA at varying concentrations and durations. Viability was assessed flow cytometrically by annexin V-FITC/PI staining and by CellTiter-Glo luminescence cell viability assay. Caspase and PARP cleavage as well as involvement of β-catenin/Lef-1 signaling was determined by immunoblotting. For caspase inhibition, BD™ ApoBlock was used. Nude mice were xenografted with JVM3 cells and treated with meta-NO-ASA, para-NO-ASA or vehicle control. The meta-isomer was entirely ineffective in inducing CLL cell apoptosis in concentrations up to 100 μM, while para-NO-ASA acted in the low micromolar range. meta-NO-ASA, in contrast to para-NO-ASA, did not alter caspase activity. While para-NO-ASA action involved inhibition of β-catenin/Lef-1 signaling, meta-NO-ASA did not show any impact on this signaling pathway. Further, meta-NO-ASA did not significantly reduce tumor growth in a CLL xenograft mouse model, while para-NO-ASA was highly potent. We conclude that positional isomerism is crucial for the antineoplastic effect of NO-ASA in CLL. It can be suggested that the para-isomer, but not the meta-isomer, generates a chemical structure which is essential for the neoplastic effect of NO-ASA.

  18. Self-consistent field theoretic simulations of amphiphilic triblock copolymer solutions: Polymer concentration and chain length effects

    Directory of Open Access Journals (Sweden)

    X.-G. Han

    2014-06-01

    Full Text Available Using the self-consistent field lattice model, polymer concentration φP and chain length N (keeping the length ratio of hydrophobic to hydrophilic blocks constant the effects on temperature-dependent behavior of micelles are studied, in amphiphilic symmetric ABA triblock copolymer solutions. When chain length is increased, at fixed φP, micelles occur at higher temperature. The variations of average volume fraction of stickers φcos and the lattice site numbers Ncols at the micellar cores with temperature are dependent on N and φP, which demonstrates that the aggregation of micelles depends on N and φP. Moreover, when φP is increased, firstly a peak appears on the curve of specific heat CV for unimer-micelle transition, and then in addition a primary peak, the secondary peak, which results from the remicellization, is observed on the curve of CV. For a long chain, in intermediate and high concentration regimes, the shape of specific heat peak markedly changes, and the peak tends to be a more broad peak. Finally, the aggregation behavior of micelles is explained by the aggregation way of amphiphilic triblock copolymer. The obtained results are helpful in understanding the micellar aggregation process.

  19. Hydration-Induced Phase Separation in Amphiphilic Polymer Matrices and its Influence on Voclosporin Release

    Energy Technology Data Exchange (ETDEWEB)

    Khan, I. John [The State Univ. of New Jersey, Piscataway, NJ (United States); Murthy, N. Sanjeeva [The State Univ. of New Jersey, Piscataway, NJ (United States); Kohn, Joachim [The State Univ. of New Jersey, Piscataway, NJ (United States)

    2015-10-30

    Voclosporin is a highly potent, new cyclosporine -- a derivative that is currently in Phase 3 clinical trials in the USA as a potential treatment for inflammatory diseases of the eye. Voclosporin represents a number of very sparingly soluble drugs that are difficult to administer. It was selected as a model drug that is dispersed within amphiphilic polymer matrices, and investigated the changing morphology of the matrices using neutron and x-ray scattering during voclosporin release and polymer resorption. The hydrophobic segments of the amphiphilic polymer chain are comprised of desaminotyrosyl-tyrosine ethyl ester (DTE) and desaminotyrosyl-tyrosine (DT), and the hydrophilic component is poly(ethylene glycol) (PEG). Water uptake in these matrices resulted in the phase separation of hydrophobic and hydrophilic domains that are a few hundred Angstroms apart. These water-driven morphological changes influenced the release profile of voclosporin and facilitated a burst-free release from the polymer. No such morphological reorganization was observed in poly(lactide-co-glycolide) (PLGA), which exhibits an extended lag period, followed by a burst-like release of voclosporin when the polymer was degraded. An understanding of the effect of polymer composition on the hydration behavior is central to understanding and controlling the phase behavior and resorption characteristics of the matrix for achieving long-term controlled release of hydrophobic drugs such as voclosporin.

  20. Photo-switching of a non-ionic azobenzene amphiphile in Langmuir and Langmuir-Blodgett films.

    Science.gov (United States)

    Piosik, Emilia; Kotkowiak, Michał; Korbecka, Izabela; Galewski, Zbigniew; Martyński, Tomasz

    2017-08-30

    The concept of programmable and reconfigurable soft matter has emerged in science in the last few decades and can be realized by photoisomerization of azobenzene derivatives. This possibility results in great application potential of these compounds in optical storage devices, molecular junctions of electronic devices, command layers of liquid crystal displays or holographic gratings. In this paper, we present the results of a study on the organization and isomerization of the non-ionic and amphiphilic methyl 4-[(E)-2-[4-(nonyloxy)phenyl]diazen-1-yl]benzoate (LCA) in a 2D layer architecture of Langmuir and Langmuir-Blodgett (LB) films supported by spectroscopic studies on LCA chloroform solutions. Our investigation has shown a significantly different molecular organization of LCA depending on the ratio of trans and cis isomers in the monolayers. Taking advantage of a relatively low packing density and aggregation strength in the cis-LCA monolayer, we demonstrated the reversible isomerization in the LB film initially formed of LCA molecules in the cis form, while in the trans-LCA monolayer this effect was not observed. Our approach allows the formation of a switchable monolayer made of the amphiphilic LCA showing liquid crystalline properties without introducing an ionic group into the molecule structure, mixing with another compound or changing the subphase pH to provide free space for the molecules' isomerization.

  1. Hydration-Induced Phase Separation in Amphiphilic Polymer Matrices and its Influence on Voclosporin Release

    Directory of Open Access Journals (Sweden)

    Joachim Kohn

    2012-10-01

    Full Text Available Voclosporin is a highly potent, new cyclosporine-A derivative that is currently in Phase 3 clinical trials in the USA as a potential treatment for inflammatory diseases of the eye. Voclosporin represents a number of very sparingly soluble drugs that are difficult to administer. We therefore selected it as a model drug that is dispersed within amphiphilic polymer matrices, and investigated the changing morphology of the matrices using neutron and x-ray scattering during voclosporin release and polymer resorption. The hydrophobic segments of the amphiphilic polymer chain are comprised of desaminotyrosyl-tyrosine ethyl ester (DTE and desaminotyrosyl-tyrosine (DT, and the hydrophilic component is poly(ethylene glycol (PEG. Water uptake in these matrices resulted in the phase separation of hydrophobic and hydrophilic domains that are a few hundred Angstroms apart. These water-driven morphological changes influenced the release profile of voclosporin and facilitated a burst-free release from the polymer. No such morphological reorganization was observed in poly(lactide-co-glycolide (PLGA, which exhibits an extended lag period, followed by a burst-like release of voclosporin when the polymer was degraded. An understanding of the effect of polymer composition on the hydration behavior is central to understanding and controlling the phase behavior and resorption characteristics of the matrix for achieving long-term controlled release of hydrophobic drugs such as voclosporin.

  2. Synthesis of an amphiphilic rhodamine derivative and characterization of its solution and thin film properties

    International Nuclear Information System (INIS)

    Aviv, Hagit; Harazi, Sivan; Schiff, Dillon; Ramon, Yoni; Tischler, Yaakov R.

    2014-01-01

    Here we present characterization of solution and thin film properties of Lissamine rhodamine B sulfonyl didodecyl amine (LRSD), an amphiphilic derivative of rhodamine. LRSD was synthesized by functionalizing Lissamine rhodamine B sulfonyl chloride (LRSC) with didodecylamine via a straightforward sulfonylation reaction. LRSD's long alkane chains make it highly soluble in chloroform, with a marked increase in brightness compared to the starting material. LRSD is shown to form well-defined robust micelles in water, without the addition of a co-surfactant and stable monolayers at the air–water interface. The greater lipophilicity of LRSD also enables doping into non-polar polymeric host matrices such as polystyrene with less aggregation and hence higher fluorescence quantum yield than LRSC or even rhodamine B. The monolayers of LRSD were prepared via Langmuir–Blodgett deposition and showed shifts in the photoluminescence peak from 575 nm to 595 nm, as the surface pressure is varied from 3 mN/m to 11 mN/m. - Highlights: • Lissamine rhodamine B sulfonyl didodecyl amine (LRSD) is soluble in chloroform. • LRSD shows robust quantum yield in solution and as a dopant in thin film. • LRSD is an amphiphilic rhodamine dye that forms compact fluorescent micelles. • LRSD forms a stable isotherm when spread at the air–water interface

  3. The nonsteroidal anti-inflammatory drug indomethacin induces heterogeneity in lipid membranes: potential implication for its diverse biological action.

    Directory of Open Access Journals (Sweden)

    Yong Zhou

    2010-01-01

    Full Text Available The nonsteroidal anti-inflammatory drug (NSAID, indomethacin (Indo, has a large number of divergent biological effects, the molecular mechanism(s for which have yet to be fully elucidated. Interestingly, Indo is highly amphiphilic and associates strongly with lipid membranes, which influence localization, structure and function of membrane-associating proteins and actively regulate cell signaling events. Thus, it is possible that Indo regulates diverse cell functions by altering micro-environments within the membrane. Here we explored the effect of Indo on the nature of the segregated domains in a mixed model membrane composed of dipalmitoyl phosphatidyl-choline (di16:0 PC, or DPPC and dioleoyl phosphatidyl-choline (di18:1 PC or DOPC and cholesterol that mimics biomembranes.Using a series of fluorescent probes in a fluorescence resonance energy transfer (FRET study, we found that Indo induced separation between gel domains and fluid domains in the mixed model membrane, possibly by enhancing the formation of gel-phase domains. This effect originated from the ability of Indo to specifically target the ordered domains in the mixed membrane. These findings were further confirmed by measuring the ability of Indo to affect the fluidity-dependent fluorescence quenching and the level of detergent resistance of membranes.Because the tested lipids are the main lipid constituents in cell membranes, the observed formation of gel phase domains induced by Indo potentially occurs in biomembranes. This marked Indo-induced change in phase behavior potentially alters membrane protein functions, which contribute to the wide variety of biological activities of Indo and other NSAIDs.

  4. Synthesis of Fluorinated Amphiphilic Block Copolymers Based on PEGMA, HEMA, and MMA via ATRP and CuAAC Click Chemistry

    Directory of Open Access Journals (Sweden)

    Fatime Eren Erol

    2014-01-01

    Full Text Available Synthesis of fluorinated amphiphilic block copolymers via atom transfer radical polymerization (ATRP and Cu(I catalyzed Huisgen 1,3-dipolar cycloaddition (CuAAC was demonstrated. First, a PEGMA and MMA based block copolymer carrying multiple side-chain acetylene moieties on the hydrophobic segment for postfunctionalization was carried out. This involves the synthesis of a series of P(HEMA-co-MMA random copolymers to be employed as macroinitiators in the controlled synthesis of P(HEMA-co-MMA-block-PPEGMA block copolymers by using ATRP, followed by a modification step on the hydroxyl side groups of HEMA via Steglich esterification to afford propargyl side-functional polymer, alkyne-P(HEMA-co-MMA-block-PPEGMA. Finally, click coupling between side-chain acetylene functionalities and 2,3,4,5,6-pentafluorobenzyl azide yielded fluorinated amphiphilic block copolymers. The obtained polymers were structurally characterized by 1H-NMR, 19F-NMR, FT-IR, and GPC. Their thermal characterizations were performed using DSC and TGA.

  5. One-Pot Synthesis of (+-Nootkatone via Dark Singlet Oxygenation of Valencene: The Triple Role of the Amphiphilic Molybdate Catalyst

    Directory of Open Access Journals (Sweden)

    Bing Hong

    2016-11-01

    Full Text Available Efficient one-pot catalytic synthesis of (+-nootkatone was performed from (+-valencene using only hydrogen peroxide and amphiphilic molybdate ions. The process required no solvent and proceeded in three cascade reactions: (i singlet oxygenation of valencene according to the ene reaction; (ii Schenck rearrangement of one hydroperoxide into the secondary β-hydroperoxide; and (iii dehydration of the hydroperoxide into the desired (+-nootkatone. The solvent effect on the hydroperoxide rearrangement is herein discussed. The amphiphilic dimethyldioctyl ammonium molybdate, which is also a balanced surfactant, played a triple role in this process, as molybdate ions catalyzed at both Step 1 and Step 3 and it allowed the rapid formation of a three-phase microemulsion system that highly facilitates product recovery. Preparative synthesis of the high added value (+-nootkatone was thus performed at room temperature with an isolated yield of 46.5%. This is also the first example of a conversion of allylic hydroperoxides into ketones catalyzed by molybdate ions.

  6. Comparative computational study of interaction of C60-fullerene and tris-malonyl-C60-fullerene isomers with lipid bilayer: relation to their antioxidant effect.

    Directory of Open Access Journals (Sweden)

    Marine E Bozdaganyan

    Full Text Available Oxidative stress induced by excessive production of reactive oxygen species (ROS has been implicated in the etiology of many human diseases. It has been reported that fullerenes and some of their derivatives-carboxyfullerenes-exhibits a strong free radical scavenging capacity. The permeation of C60-fullerene and its amphiphilic derivatives-C3-tris-malonic-C60-fullerene (C3 and D3-tris-malonyl-C60-fullerene (D3-through a lipid bilayer mimicking the eukaryotic cell membrane was studied using molecular dynamics (MD simulations. The free energy profiles along the normal to the bilayer composed of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC for C60, C3 and D3 were calculated. We found that C60 molecules alone or in clusters spontaneously translocate to the hydrophobic core of the membrane and stay inside the bilayer during the whole period of simulation time. The incorporation of cluster of fullerenes inside the bilayer changes properties of the bilayer and leads to its deformation. In simulations of the tris-malonic fullerenes we discovered that both isomers, C3 and D3, adsorb at the surface of the bilayer but only C3 tends to be buried in the area of the lipid headgroups forming hydrophobic contacts with the lipid tails. We hypothesize that such position has implications for ROS scavenging mechanism in the specific cell compartments.

  7. Study of antineoplastic action of novel isomeric derivatives of 4-thiazolidinone

    Directory of Open Access Journals (Sweden)

    М. R. Fil

    2014-12-01

    Full Text Available Pyrazole- and aryl-substituted derivatives of 4-thiazolidinone belong to a perspective group of compounds with potential antitumor action. Earlier, we have demonstrated high toxicity in vitro of several 4-thiazolidinones derivatives towards tumor cell lines. To further enhance the antitumor activity of novel 4-thiazolidinones, their chemical scaffold was optimized, and new pyrazole-thiazolidinones were synthesized. That allowed us to combine in one molecule the potential pharmacophore centres of previously tested compounds. As a result, “hybrid” 4-thiazolidinones exhibit higher toxicity in vitro toward tumor cells of various origin. The molecular mechanisms of antineoplastic activity of these compounds and intensity of induction of apoptosis strongly depended on the position of the substituent in the thiazolidinone cycle. In particular, Les-3661 compound, containing pyrazoline fragment in the 4th position of thiazolidinone core, exhibits 14 times higher cytotoxic activity towards tumor cells (LC50 = 3 µM in comparison to its 2-substituted isomer Les-3713 (LC50 = 42 µM. It is demonstrated that in terms of underlying molecular mechanisms for cytotoxic effect the Les-3661 compound induced caspase-8 and caspase-9 dependent mixed-type of apoptosis, while Les-3713 induced apoptosis mediated only by the caspase-8.

  8. Lysosomotropic cationic amphiphilic drugs inhibit adipocyte differentiation in 3T3-L1K cells via accumulation in cells and phospholipid membranes, and inhibition of autophagy.

    Science.gov (United States)

    Kagebeck, Patrik; Nikiforova, Violetta; Brunken, Lars; Easwaranathan, Arrabi; Ruegg, Joelle; Cotgreave, Ian; Munic Kos, Vesna

    2018-04-05

    Some cationic amphiphilic drugs (CADs) have been individually reported to interfere with the differentiation of immune system cells, such as macrophages and dendritic cells. To investigate the possible generic nature of this process, in this study we aimed to see whether these drugs are capable of interfering with the differentiation of adipocytes. Further, we investigated whether this feature might be connected to the lysosomotropic character of these drugs, and their disturbance of intracellular membrane trafficking rather than to the individual pharmacologic properties of each drug. Thus, for the selected set of compounds consisting of seven structurally and pharmacologically diverse CADs and three non-CAD controls we have measured the impact on differentiation of 3T3-L1K murine preadipocytes to adipocytes. We conclude that CADs indeed inhibit adipocyte differentiation, as shown morphologically, at the level of lipid droplet formation and on the expression of genetic markers of adipocytes. Furthermore, the intensity of this inhibitory effect was found to strongly positively correlate with the extent of drug accumulation in adipocytes, with their affinity for phospholipid membranes, as well as with their ability to induce phospholipidosis and inhibit autophagy. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. Evaluation of chromatographic conditions in reversed phase liquid chromatography-mass spectrometry systems for fingerprinting of polar and amphiphilic plant metabolites

    DEFF Research Database (Denmark)

    Nielsen, Nikoline Juul; Tomasi, Giorgio; Christensen, Jan H.

    2016-01-01

    Metabolic fingerprinting is a relatively young scientific discipline requiring robust, yet flexible and fit-for-purpose analytical methods. Here, we introduce a simple approach to select reversed phase LC systems with electrospray MS detection for fingerprinting of polar and amphiphilic plant met...

  10. Nanostructures and surface hydrophobicity of self-assembled thermosets involving epoxy resin and poly(2,2,2-trifluoroethyl acrylate)-block-poly(ethylene oxide) amphiphilic diblock copolymer.

    Science.gov (United States)

    Yi, Fangping; Zheng, Sixun; Liu, Tianxi

    2009-02-19

    Poly(2,2,2-trifluoroethyl acrylate)-block-poly(ethylene oxide) (PTFEA-b-PEO) amphiphilic diblock copolymer was synthesized via the reversible addition-fragmentation transfer polymerization of 2,2,2-triffluroethyl acrylate with dithiobenzoyl-terminated poly(ethylene oxide) as a chain-transfer agent. The amphiphilic diblock copolymer was incorporated into epoxy resin to prepare the nanostructured epoxy thermosets. The nanostructures were investigated by means of atomic force microscopy, small-angle X-ray scattering, and dynamic mechanical analysis. In terms of the miscibility of the subchains of the block copolymer with epoxy after and before curing reaction, it is judged that the formation of the nanostructures follows the mechanism of self-assembly. The static contact angle measurements indicate that the nanostructured thermosets containing PTFEA-b-PEO diblock copolymer displayed a significant enhancement in surface hydrophobicity as well as a reduction in surface free energy. The improvement in surface properties was ascribed to the enrichment of the fluorine-containing subchain (i.e., PTFEA block) of the amphiphilic diblock copolymer on the surface of the nanostructured thermosets, which was evidenced by surface atomic force microscopy and energy-dispersive X-ray spectroscopy.

  11. Tipping the Scale from Disorder to Alpha-helix: Folding of Amphiphilic Peptides in the Presence of Macroscopic and Molecular Interfaces.

    Directory of Open Access Journals (Sweden)

    Cahit Dalgicdir

    2015-08-01

    Full Text Available Secondary amphiphilicity is inherent to the secondary structural elements of proteins. By forming energetically favorable contacts with each other these amphiphilic building blocks give rise to the formation of a tertiary structure. Small proteins and peptides, on the other hand, are usually too short to form multiple structural elements and cannot stabilize them internally. Therefore, these molecules are often found to be structurally ambiguous up to the point of a large degree of intrinsic disorder in solution. Consequently, their conformational preference is particularly susceptible to environmental conditions such as pH, salts, or presence of interfaces. In this study we use molecular dynamics simulations to analyze the conformational behavior of two synthetic peptides, LKKLLKLLKKLLKL (LK and EAALAEALAEALAE (EALA, with built-in secondary amphiphilicity upon forming an alpha-helix. We use these model peptides to systematically study their aggregation and the influence of macroscopic and molecular interfaces on their conformational preferences. We show that the peptides are neither random coils in bulk water nor fully formed alpha helices, but adopt multiple conformations and secondary structure elements with short lifetimes. These provide a basis for conformation-selection and population-shift upon environmental changes. Differences in these peptides' response to macroscopic and molecular interfaces (presented by an aggregation partner can be linked to their inherent alpha-helical tendencies in bulk water. We find that the peptides' aggregation behavior is also strongly affected by presence or absence of an interface, and rather subtly depends on their surface charge and hydrophobicity.

  12. Controlled Synthesis of AB2 amphiphilic triarm star-shaped block copolymers by ring-opening polymerization

    OpenAIRE

    Petrova, Svetla; Riva, Raphaël; Jérôme, Christine; Lecomte, Philippe; Mateva, Rosa

    2009-01-01

    This paper describes the synthesis of a novel amphiphilic AB2 triarm star-shaped copolymer with A = non-toxic and biocompatible hydrophilic poly(ethylene oxide) (PEO) and B = biodegradable and hydrophobic poly(ε-caprolactone) (PCL). A series of AB2 triarm star-shaped copolymers with different molecular weights for the PCL block were successfully synthesized by a three-step procedure. α-methoxy-ω-epoxy-poly(ethylene oxide) (PEO-epoxide) was first synthesized by the nucleophilic substitution of...

  13. Avanti lipid tools: connecting lipids, technology, and cell biology.

    Science.gov (United States)

    Sims, Kacee H; Tytler, Ewan M; Tipton, John; Hill, Kasey L; Burgess, Stephen W; Shaw, Walter A

    2014-08-01

    Lipid research is challenging owing to the complexity and diversity of the lipidome. Here we review a set of experimental tools developed for the seasoned lipid researcher, as well as, those who are new to the field of lipid research. Novel tools for probing protein-lipid interactions, applications for lipid binding antibodies, enhanced systems for the cellular delivery of lipids, improved visualization of lipid membranes using gold-labeled lipids, and advances in mass spectrometric analysis techniques will be discussed. Because lipid mediators are known to participate in a host of signal transduction and trafficking pathways within the cell, a comprehensive lipid toolbox that aids the science of lipidomics research is essential to better understand the molecular mechanisms of interactions between cellular components. This article is part of a Special Issue entitled Tools to study lipid functions. Copyright © 2014. Published by Elsevier B.V.

  14. Adsorption, folding, and packing of an amphiphilic peptide at the air/water interface.

    Science.gov (United States)

    Engin, Ozge; Sayar, Mehmet

    2012-02-23

    Peptide oligomers play an essential role as model compounds for identifying key motifs in protein structure formation and protein aggregation. Here, we present our results, based on extensive molecular dynamics simulations, on adsorption, folding, and packing within a surface monolayer of an amphiphilic peptide at the air/water interface. Experimental results suggest that these molecules spontaneously form ordered monolayers at the interface, adopting a β-hairpin-like structure within the surface layer. Our results reveal that the β-hairpin structure can be observed both in bulk and at the air/water interface. However, the presence of an interface leads to ideal partitioning of the hydrophobic and hydrophilic residues, and therefore reduces the conformational space for the molecule and increases the stability of the hairpin structure. We obtained the adsorption free energy of a single β-hairpin at the air/water interface, and analyzed the enthalpic and entropic contributions. The adsorption process is favored by two main factors: (1) Free-energy reduction due to desolvation of the hydrophobic side chains of the peptide and release of the water molecules which form a cage around these hydrophobic groups in bulk water. (2) Reduction of the total air/water contact area at the interface upon adsorption of the peptide amphiphile. By performing mutations on the original molecule, we demonstrated the relative role of key design features of the peptide. Finally, by analyzing the potential of mean force among two peptides at the interface, we investigated possible packing mechanisms for these molecules within the surface monolayer. © 2012 American Chemical Society

  15. Drug Release and Skin Permeation from Lipid Liquid Crystalline Phases

    Science.gov (United States)

    Costa-Balogh, F. O.; Sparr, E.; Sousa, J. J. S.; Pais, A. A. C. C.

    We have studied drug release and skin permeation from several different liquid crystalline lipid formulations that may be used to control the respective release rates. We have studied the release and permeation through human skin of a water-soluble and amphiphilic drug, propranolol hydrochloride, from several formulations prepared with monoolein and phytantriol as permeation enhancers and controlled release excipients. Diolein and cineol were added to selected formulations. We observed that viscosity decreases with drug load, wich is compatible with the occurrence of phase changes. Diolein stabilizes the bicontinuous cubic phases leading to an increase in viscosity and sustained release of the drug. The slowest release was found for the cubic phases with higher viscosity. Studies on skin permeation showed that these latter formulations also presented lower permeability than the less viscous monoolein lamellar phases. Formulations containing cineol originated higher permeability with higher enhancement ratios. Thus, the various formulations are adapted to different circumstances and delivery routes. While a slow release is usually desired for drug sustained delivery, the transdermal route may require a faster release. Lamellar phases, which are less viscous, are more adapted to transdermal applications. Thus, systems involving lamellar phases of monoolein and cineol are good candidates to be used as skin permeation enhancers for propranolol hydrochloride.

  16. Spontaneous charged lipid transfer between lipid vesicles.

    Science.gov (United States)

    Richens, Joanna L; Tyler, Arwen I I; Barriga, Hanna M G; Bramble, Jonathan P; Law, Robert V; Brooks, Nicholas J; Seddon, John M; Ces, Oscar; O'Shea, Paul

    2017-10-03

    An assay to study the spontaneous charged lipid transfer between lipid vesicles is described. A donor/acceptor vesicle system is employed, where neutrally charged acceptor vesicles are fluorescently labelled with the electrostatic membrane probe Fluoresceinphosphatidylethanolamine (FPE). Upon addition of charged donor vesicles, transfer of negatively charged lipid occurs, resulting in a fluorescently detectable change in the membrane potential of the acceptor vesicles. Using this approach we have studied the transfer properties of a range of lipids, varying both the headgroup and the chain length. At the low vesicle concentrations chosen, the transfer follows a first-order process where lipid monomers are transferred presumably through the aqueous solution phase from donor to acceptor vesicle. The rate of transfer decreases with increasing chain length which is consistent with energy models previously reported for lipid monomer vesicle interactions. Our assay improves on existing methods allowing the study of a range of unmodified lipids, continuous monitoring of transfer and simplified experimental procedures.

  17. Development of a new LDL-based transport system for hydrophobic/amphiphilic drug delivery to cancer cells.

    Science.gov (United States)

    Huntosova, Veronika; Buzova, Diana; Petrovajova, Dana; Kasak, Peter; Nadova, Zuzana; Jancura, Daniel; Sureau, Franck; Miskovsky, Pavol

    2012-10-15

    Low-density lipoproteins (LDL), a natural in vivo carrier of cholesterol in the vascular system, play a key role in the delivery of hydrophobic/amphiphilic photosensitizers to tumor cells in photodynamic therapy of cancer. To make this delivery system even more efficient, we have constructed a nano-delivery system by coating of LDL surface by dextran. Fluorescence spectroscopy, confocal fluorescence imaging, stopped-flow experiments and flow-cytometry were used to characterize redistribution of hypericin (Hyp), a natural occurring potent photosensitizer, loaded in LDL/dextran complex to free LDL molecules as well as to monitor cellular uptake of Hyp by U87-MG cells. It is shown that the redistribution process of Hyp between LDL molecules is significantly suppressed by dextran coating of LDL surface. The modification of LDL molecules by dextran does not inhibit their recognition by cellular LDL receptors and U-87 MG cellular uptake of Hyp loaded in LDL/dextran complex appears to be similar to that one observed for Hyp transported by unmodified LDL particles. Thus, it is proposed that dextran modified LDL molecules could be used as a basis for construction of a drug transport system for targeted delivery of hydrophobic/amphiphilic drugs to cancer cells expressing high level of LDL receptors. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. Molecular fouling resistance of zwitterionic and amphiphilic initiated chemically vapor-deposited (iCVD) thin films

    Energy Technology Data Exchange (ETDEWEB)

    Yang, R; Goktekin, E; Wang, MH; Gleason, KK

    2014-08-08

    Biofouling is a universal problem in various applications ranging from water purification to implantable biomedical devices. Recent advances in surface modification have created a rich library of antifouling surface chemistries, many of which can be categorized into one of the two groups: hydrophilic surfaces or amphiphilic surfaces. We report the straightforward preparation of antifouling thin film coatings in both categories via initiated chemical vapor deposition. A molecular force spectroscopy-based method is demonstrated as a rapid and quantitative assessment tool for comparing the differences in antifouling characteristics. The fouling propensity of single molecules, as opposed to bulk protein solution or bacterial culture, is assessed. This method allows for the interrogation of molecular interaction without the complication resulted from protein conformational change or micro-organism group interactions. The molecular interaction follows the same trend as bacterial adhesion results obtained previously, demonstrating that molecular force probe is a valid method for the quantification and mechanistic examination of fouling. In addition, the molecular force spectroscopy-based method is able to distinguish differences in antifouling capability that is not resolvable by traditional static protein adsorption tests. To lend further insight into the intrinsic fouling resistance of zwitterionic and amphiphilic surface chemistries, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, advancing and receding water contact angles, and atomic force microscopy are used to elucidate the film properties that are relevant to their antifouling capabilities.

  19. A Novel Insight into the Cardiotoxicity of Antineoplastic Drug Doxorubicin

    Directory of Open Access Journals (Sweden)

    Zbynek Heger

    2013-10-01

    Full Text Available Doxorubicin is a commonly used antineoplastic agent in the treatment of many types of cancer. Little is known about the interactions of doxorubicin with cardiac biomolecules. Serious cardiotoxicity including dilated cardiomyopathy often resulting in a fatal congestive heart failure may occur as a consequence of chemotherapy with doxorubicin. The purpose of this study was to determine the effect of exposure to doxorubicin on the changes in major amino acids in tissue of cardiac muscle (proline, taurine, glutamic acid, arginine, aspartic acid, leucine, glycine, valine, alanine, isoleucine, threonine, lysine and serine. An in vitro interaction study was performed as a comparison of amino acid profiles in heart tissue before and after application of doxorubicin. We found that doxorubicin directly influences myocardial amino acid representation even at low concentrations. In addition, we performed an interaction study that resulted in the determination of breaking points for each of analyzed amino acids. Lysine, arginine, β-alanine, valine and serine were determined as the most sensitive amino acids. Additionally we compared amino acid profiles of myocardium before and after exposure to doxorubicin. The amount of amino acids after interaction with doxorubicin was significantly reduced (p = 0.05. This fact points at an ability of doxorubicin to induce changes in quantitative composition of amino acids in myocardium. Moreover, this confirms that the interactions between doxorubicin and amino acids may act as another factor most likely responsible for adverse effects of doxorubicin on myocardium.

  20. Amphiphilic copolymers based on polyoxazoline and grape seed vegetable oil derivatives: self-assemblies and dynamic light scattering

    Energy Technology Data Exchange (ETDEWEB)

    Travelet, Christophe, E-mail: Christophe.Travelet@cermav.cnrs.fr [Universite Joseph Fourier (UJF), Institut de Chimie Moleculaire de Grenoble (ICMG-FR 2607 CNRS), PolyNat Carnot institute, Arcane LabEx, domaine universitaire de Grenoble, Centre de Recherches sur les Macromolecules Vegetales - CERMAV-UPR 5301 CNRS (France); Stemmelen, Mylene; Lapinte, Vincent [Universite de Montpellier II, Institut Charles Gerhardt Montpellier (UMR 5253 CNRS-UM2-UM1-ENSCM), equipe ingenierie et architectures macromoleculaires (France); Dubreuil, Frederic [Universite Joseph Fourier (UJF), Institut de Chimie Moleculaire de Grenoble (ICMG-FR 2607 CNRS), PolyNat Carnot institute, Arcane LabEx, domaine universitaire de Grenoble, Centre de Recherches sur les Macromolecules Vegetales - CERMAV-UPR 5301 CNRS (France); Robin, Jean-Jacques [Universite de Montpellier II, Institut Charles Gerhardt Montpellier (UMR 5253 CNRS-UM2-UM1-ENSCM), equipe ingenierie et architectures macromoleculaires (France); and others

    2013-06-15

    The self-assembly in solution of original structures of amphiphilic partially natural copolymers based on polyoxazoline [more precisely poly(2-methyl-2-oxazoline) (POx)] and grape seed vegetable oil derivatives (linear, T-, and trident-structure) is investigated. The results show that such systems are found, using dynamic light scattering (DLS), to spontaneously self-organize into monomodal, narrow-size, and stable nanoparticles in aqueous medium. The obtained hydrodynamic diameters (D{sub h}) range from 8.6 to 32.5 nm. Specifically, such size increases strongly with increasing natural block (i.e., lipophilic species) length due to higher hydrophobic interactions (from 10.1 nm for C{sub 19} to 19.2 nm for C{sub 57}). Furthermore, increasing the polyoxazoline (i.e., hydrophilic block) length leads to a moderate linear increase of the D{sub h}-values. Therefore, the first-order size effect comes from the natural lipophilic block, whereas the characteristic size can be tuned more finely (i.e., in a second-order) by choosing appropriately the polyoxazoline length. The DLS results in terms of characteristic size are corroborated using nanoparticle tracking analysis (NTA), and also by atomic force microscopy (AFM) and transmission electron microscopy (TEM) imaging where well-defined spherical and individual nanoparticles exhibit a very good mechanical resistance upon drying. Moreover, changing the lipophilic block architecture from linear to T-shape, while keeping the same molar mass, generates a branching and thus a shrinking by a factor of 2 of the nanoparticle volume, as observed by DLS. In this paper, it is clearly shown that the self-assemblies of amphiphilic block copolymer obtained from grape seed vegetable oil derivatives (sustainable renewable resources) as well as their tunability are of great interest for biomass valorization at the nanoscale level [continuation of the article by Stemmelen et al. (Polym Chem 4:1445-1458, 2013)].Graphical AbstractAmphiphilic

  1. Amphiphilic copolymers based on polyoxazoline and grape seed vegetable oil derivatives: self-assemblies and dynamic light scattering

    International Nuclear Information System (INIS)

    Travelet, Christophe; Stemmelen, Mylène; Lapinte, Vincent; Dubreuil, Frédéric; Robin, Jean-Jacques

    2013-01-01

    The self-assembly in solution of original structures of amphiphilic partially natural copolymers based on polyoxazoline [more precisely poly(2-methyl-2-oxazoline) (POx)] and grape seed vegetable oil derivatives (linear, T-, and trident-structure) is investigated. The results show that such systems are found, using dynamic light scattering (DLS), to spontaneously self-organize into monomodal, narrow-size, and stable nanoparticles in aqueous medium. The obtained hydrodynamic diameters (D h ) range from 8.6 to 32.5 nm. Specifically, such size increases strongly with increasing natural block (i.e., lipophilic species) length due to higher hydrophobic interactions (from 10.1 nm for C 19 to 19.2 nm for C 57 ). Furthermore, increasing the polyoxazoline (i.e., hydrophilic block) length leads to a moderate linear increase of the D h -values. Therefore, the first-order size effect comes from the natural lipophilic block, whereas the characteristic size can be tuned more finely (i.e., in a second-order) by choosing appropriately the polyoxazoline length. The DLS results in terms of characteristic size are corroborated using nanoparticle tracking analysis (NTA), and also by atomic force microscopy (AFM) and transmission electron microscopy (TEM) imaging where well-defined spherical and individual nanoparticles exhibit a very good mechanical resistance upon drying. Moreover, changing the lipophilic block architecture from linear to T-shape, while keeping the same molar mass, generates a branching and thus a shrinking by a factor of 2 of the nanoparticle volume, as observed by DLS. In this paper, it is clearly shown that the self-assemblies of amphiphilic block copolymer obtained from grape seed vegetable oil derivatives (sustainable renewable resources) as well as their tunability are of great interest for biomass valorization at the nanoscale level [continuation of the article by Stemmelen et al. (Polym Chem 4:1445–1458, 2013)].Graphical AbstractAmphiphilic copolymers based

  2. A Lipophilic IR-780 Dye-Encapsulated Zwitterionic Polymer-Lipid Micellar Nanoparticle for Enhanced Photothermal Therapy and NIR-Based Fluorescence Imaging in a Cervical Tumor Mouse Model

    Directory of Open Access Journals (Sweden)

    Santhosh Kalash Rajendrakumar

    2018-04-01

    Full Text Available To prolong blood circulation and avoid the triggering of immune responses, nanoparticles in the bloodstream require conjugation with polyethylene glycol (PEG. However, PEGylation hinders the interaction between the nanoparticles and the tumor cells and therefore limits the applications of PEGylated nanoparticles for therapeutic drug delivery. To overcome this limitation, zwitterionic materials can be used to enhance the systemic blood circulation and tumor-specific delivery of hydrophobic agents such as IR-780 iodide dye for photothermal therapy. Herein, we developed micellar nanoparticles using the amphiphilic homopolymer poly(12-(methacryloyloxydodecyl phosphorylcholine (PCB-lipid synthesized via reversible addition–fragmentation chain transfer (RAFT polymerization. The PCB-lipid can self-assemble into micelles and encapsulate IR-780 dye (PCB-lipid–IR-780. Our results demonstrated that PCB-lipid–IR-780 nanoparticle (NP exhibited low cytotoxicity and remarkable photothermal cytotoxicity to cervical cancer cells (TC-1 upon near-infrared (NIR laser irradiation. The biodistribution of PCB-lipid–IR-780 showed higher accumulation of PCB-lipid–IR-780 than that of free IR-780 in the TC-1 tumor. Furthermore, following NIR laser irradiation of the tumor region, the PCB-lipid–IR-780 accumulated in the tumor facilitated enhanced tumor ablation and subsequent tumor regression in the TC-1 xenograft model. Hence, these zwitterionic polymer-lipid hybrid micellar nanoparticles show great potential for cancer theranostics and might be beneficial for clinical applications.

  3. Preliminary study of cell metabolism, by use of NBT test, determination the intensity of lipid peroxidation and antioxidant activity

    Directory of Open Access Journals (Sweden)

    Diana BEI

    2009-05-01

    Full Text Available Otto Warburg, in the early part of the 20th century, originated a hypothesis, that the cause of cancer is primarily a defect in energy metabolism.A decrease in the capacity of mitochondria to reduce NAD(P, together with a decline in the NAD(PH/NAD(P redox couple, uncouples oxidative phosphorylation, lead to depletion of ATP and decrease the cell viability.Nitro-bleu tetrazolium have been used to assay cell proliferation and viability. The method to measure cell proliferation is based on enzymatic cleavage of the tetrazolium salts to a water-soluble formazan dye.Succinate-tetrazolium reductase, is an enzymatic sistem, which belongs to the respiratory chain of the mitochondria and it is active only in viable cells. The reagent diffuses into the cells and it is cleaved to formazan. The absorption change is measured and analysed.Free radicals such as superoxide, can cause a damage in cellular components, but several antioxidants inhibiting the lipid peroxidation and limiting the level of free radicals in cells.In the present study we had in view the proliferation and viability of leukemia cells during antineoplastic treatment along with the alteration of the serum level of malondialdehyde (MDA and ceruloplasmin (CP. With serum level of malondialdehyde we monitored the presence of the lipid peroxidation by the reactive oxygen species, and with the oxidized ceruloplasmin level in blood serum we evidenced the activity of antioxidant system in blood.

  4. Synthesis and characterization of biodegradable poly (ethylene glycol) and poly (caprolactone diol) end capped poly (propylene fumarate) cross linked amphiphilic hydrogel as tissue engineering scaffold material.

    Science.gov (United States)

    Krishna, Lekshmi; Jayabalan, Muthu

    2009-12-01

    Biodegradable poly (caprolactone diol-co-propylene fumarate-co-ethylene glycol) amphiphilic polymer with poly (ethylene glycol) and poly (caprolactone diol) chain ends (PCL-PPF-PEG) was prepared. PCL-PPF-PEG undergoes fast setting with acrylamide (aqueous solution) by free radical polymerization and produces a crosslinked hydrogel. The cross linked and freeze-dried amphiphilic material has porous and interconnected network. It undergoes higher degree of swelling and water absorption to form hydrogel with hydrophilic and hydrophobic domains at the surface and appreciable tensile strength. The present hydrogel is compatible with L929 fibroblast cells. PCL-PPF-PEG/acrylamide hydrogel is a candidate scaffold material for tissue engineering applications.

  5. Inclusion Complexes of a New Family of Non-Ionic Amphiphilic Dendrocalix[4]arene and Poorly Water-Soluble Drugs Naproxen and Ibuprofen

    Directory of Open Access Journals (Sweden)

    Khalid Khan

    2017-05-01

    Full Text Available The inclusion complexes of a new family of nonionic amphiphilic calix[4]arenes with the anti-inflammatory hydrophobic drugs naproxen (NAP and ibuprofen (IBP were investigated. The effects of the alkyl chain’s length and the inner core of calix[4]arenes on the interaction of the two drugs with the calix[4]arenes were explored. The inclusion complexes of Amphiphiles 1a–c with NAP and IBP increased the solubility of these drugs in aqueous media. The interaction of 1a–c with the drugs in aqueous media was investigated through fluorescence, molecular modeling, and 1H-NMR analysis. TEM studies further supported the formation of inclusion complexes. The length of lipophilic alkyl chains and the intrinsic cyclic nature of cailx[4]arene derivatives 1a–c were found to have a significant impact on the solubility of NAP and IBP in pure water.

  6. Core–Shell Structure and Aggregation Number of Micelles Composed of Amphiphilic Block Copolymers and Amphiphilic Heterografted Polymer Brushes Determined by Small-Angle X-ray Scattering

    Energy Technology Data Exchange (ETDEWEB)

    Szymusiak, Magdalena; Kalkowski, Joseph; Luo, Hanying; Donovan, Alexander J.; Zhang, Pin; Liu, Chang; Shang, Weifeng; Irving, Thomas; Herrera-Alonso, Margarita; Liu, Ying (JHU); (IIT); (UIC)

    2017-08-31

    A large group of functional nanomaterials employed in biomedical applications, including targeted drug delivery, relies on amphiphilic polymers to encapsulate therapeutic payloads via self-assembly processes. Knowledge of the micelle structures will provide critical insights into design of polymeric drug delivery systems. Core–shell micelles composed of linear diblock copolymers poly(ethylene glycol)-b-poly(caprolactone) (PEG-b-PCL), poly(ethylene oxide)-b-poly(lactic acid) (PEG-b-PLA), as well as a heterografted brush consisting of a poly(glycidyl methacrylate) backbone with PEG and PLA branches (PGMA-g-PEG/PLA) were characterized by dynamic light scattering (DLS) and small-angle X-ray scattering (SAXS) measurements to gain structural information regarding the particle morphology, core–shell size, and aggregation number. The structural information at this quasi-equilibrium state can also be used as a reference when studying the kinetics of polymer micellization.

  7. Core–Shell Structure and Aggregation Number of Micelles Composed of Amphiphilic Block Copolymers and Amphiphilic Heterografted Polymer Brushes Determined by Small-Angle X-ray Scattering

    Energy Technology Data Exchange (ETDEWEB)

    Szymusiak, Magdalena [Department; Kalkowski, Joseph [Department; Luo, Hanying [Department; Donovan, Alexander J. [Department; Zhang, Pin [Department; Liu, Chang [Department; Shang, Weifeng [Department; Irving, Thomas [Department; Herrera-Alonso, Margarita [Department; Liu, Ying [Department; Department

    2017-08-16

    A large group of functional nanomaterials employed in biomedical applications, including targeted drug delivery, relies on amphiphilic polymers to encapsulate therapeutic payloads via self-assembly processes. Knowledge of the micelle structures will provide critical insights into design of polymeric drug delivery systems. Core–shell micelles composed of linear diblock copolymers poly(ethylene glycol)-b-poly(caprolactone) (PEG-b-PCL), poly(ethylene oxide)-b-poly(lactic acid) (PEG-b-PLA), as well as a heterografted brush consisting of a poly(glycidyl methacrylate) backbone with PEG and PLA branches (PGMA-g-PEG/PLA) were characterized by dynamic light scattering (DLS) and small-angle X-ray scattering (SAXS) measurements to gain structural information regarding the particle morphology, core–shell size, and aggregation number. The structural information at this quasi-equilibrium state can also be used as a reference when studying the kinetics of polymer micellization.

  8. In Situ Mapping of the Molecular Arrangement of Amphiphilic Dye Molecules at the TiO 2 Surface of Dye-Sensitized Solar Cells

    KAUST Repository

    Voï tchovsky, Kislon; Ashari-Astani, Negar; Tavernelli, Ivano; Té treault, Nicolas; Rothlisberger, Ursula; Stellacci, Francesco; Grä tzel, Michael; Harms, Hauke A.

    2015-01-01

    © 2015 American Chemical Society. Amphiphilic sensitizers are central to the function of dye-sensitized solar cells. It is known that the cell's performance depends on the molecular arrangement and the density of the dye on the semiconductor surface

  9. Analysis of the aggregation structure from amphiphilic block copolymers in solutions by small-angle x-ray scattering

    CERN Document Server

    Rong Li Xia; Wang Jun; Wei Liu He; Li Fu Mian; Li Zi Chen

    2002-01-01

    The aggregation structure of polystyrene-p vinyl benzoic amphiphilic block copolymers which were prepared in different conditions was investigated by synchrotron radiation small-angle x-ray scattering (SAXS). The micelle was self-assembled in selective solvents of the block copolymers. Authors' results demonstrate that the structure of the micelle depends on the factors, such as the composition of the copolymers, the nature of the solvent and the concentration of the solution

  10. The membrane interaction of amphiphilic model peptides affects phosphatidylserine headgroup and acyl chain order and dynamics. Application of the phospholipid headgroup electrometer concept to phosphatidylserine

    International Nuclear Information System (INIS)

    de Kroon, A.I.P.M.; Killian, J.A.; de Gier, J.; de Kruijff, B.

    1991-01-01

    Deuterium nuclear magnetic resonance ( 2 H NMR) was used to study the interaction of amphiphilic model peptides with model membranes consisting of 1,2-dioleoyl-sn-glycero-3-phospho-L-serine deuterated either at the β-position of the serine moiety ([2- 2 H]DOPS) or at the 11-position of the acyl chains ([11,11- 2 H 2 ]DOPS). The peptides are derived from the sequences H-Ala-Met-Leu-Trp-Ala-OH and H-Arg-Met-Leu-Trp-Ala-OH and contain a positive charge of +1 or +2 at the amino terminus or one positive charge at each end of the molecule. Upon titration of dispersions of DOPS with the peptides, the divalent peptides show a similar extent of binding to the DOPS bilyers, which is larger than that of the single charged peptide. Under these conditions the values of the quadrupolar splitting of both [2- 2 H]DOPS and [11,11- 2 H 2 ]DOPS are decreased, indicating that the peptides reduce the order of both the DOPS headgroup and the acyl chains. The extent of the decrease depends on the amount of peptide bound and on the position of the charged moieties in the peptide molecule. Titrations of DOPS with poly(L-lysine) 100 , which were included for reasons of comparison, reveal increased Δv q values. When the peptide-lipid titrations are carried out without applying a freeze-thaw procedure to achieve full equilibration, two-component 2 H NMR spectra occur. The apparently limited accessibility of the lipid to the peptides under these circumstances is discussed in relation to the ability of the peptides to exhibit transbilayer movement. 2 H spin-lattice relaxation time T1 measurements demonstrate a decrease of the rates of motion of both headgroup and acyl chains of DOPS in the presence of the peptides

  11. Electrophysiological Assessment of a Peptide Amphiphile Nanofiber Nerve Graft for Facial Nerve Repair.

    Science.gov (United States)

    Greene, Jacqueline J; McClendon, Mark T; Stephanopoulos, Nicholas; Álvarez, Zaida; Stupp, Samuel I; Richter, Claus-Peter

    2018-04-27

    Facial nerve injury can cause severe long-term physical and psychological morbidity. There are limited repair options for an acutely transected facial nerve not amenable to primary neurorrhaphy. We hypothesize that a peptide amphiphile nanofiber neurograft may provide the nanostructure necessary to guide organized neural regeneration. Five experimental groups were compared, animals with 1) an intact nerve, 2) following resection of a nerve segment, and following resection and immediate repair with either a 3) autograft (using the resected nerve segment), 4) neurograft, or 5) empty conduit. The buccal branch of the rat facial nerve was directly stimulated with charge balanced biphasic electrical current pulses at different current amplitudes while nerve compound action potentials (nCAPs) and electromygraphic (EMG) responses were recorded. After 8 weeks, the proximal buccal branch was surgically re-exposed and electrically evoked nCAPs were recorded for groups 1-5. As expected, the intact nerves required significantly lower current amplitudes to evoke an nCAP than those repaired with the neurograft and autograft nerves. For other electrophysiologic parameters such as latency and maximum nCAP, there was no significant difference between the intact, autograft and neurograft groups. The resected group had variable responses to electrical stimulation, and the empty tube group was electrically silent. Immunohistochemical analysis and TEM confirmed myelinated neural regeneration. This study demonstrates that the neuroregenerative capability of peptide amphiphile nanofiber neurografts is similar to the current clinical gold standard method of repair and holds potential as an off-the-shelf solution for facial reanimation and potentially peripheral nerve repair. This article is protected by copyright. All rights reserved.

  12. Effect of electrostatic interaction between fluoxetine and lipid membranes on the partitioning of fluoxetine investigated using second derivative spectrophotometry and FTIR.

    Science.gov (United States)

    Do, Tien T T; Dao, Uyen P N; Bui, Huong T; Nguyen, Trang T

    2017-10-01

    The interaction between a drug molecule and lipid bilayers is highly important regarding the pharmaceutical activity of the drug. In this study, the interaction of fluoxetine, a well-known selective serotonin reuptake inhibitor antidepressant and lipid bilayers composed of 1,2-dipalmitoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (DPPG) and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) was studied from the aspect of electrostatics using second derivative spectrophotometry and Fourier transform infrared spectroscopy (FTIR) in order to provide insights into the drug behavior. Changing pH from 7.4 to 9.5 to increases the neutral state of fluoxetine, the partitioning of fluoxetine into the zwitterionic DPPC large unilamellar vesicles (LUVs) was increased whereas it was reduced into the negatively charged DPPG LUVs. Fluoxetine was found to exhibit a disordering effect on the acyl chains of DPPC and DPPG bilayers upon its partitioning. In addition, increasing concentration of NaCl lessened the binding of fluoxetine into DPPG bilayers due to the reduction in electrostatic attraction between positively charged fluoxetine and negatively charged DPPG LUVs. In addition, the FTIR study revealed that increasing the NaCl concentration could trigger the shift to higher frequency of the CH 2 stretching as well as the notable blue shift in the PO 2 - regions of DPPG, indicating that fluoxetine had deeper penetration into DPPG LUVs. The differences in the NaCl concentration showed a negligible effect on the incorporation of fluoxetine into the zwitterionic DPPC LUVs. In summary, the electrostatic interaction plays an important role on the partitioning of a cationic amphiphilic SSIR drug into the lipid bilayers and the drug partitioning induces the lipids' conformational change. These imply a possible influence on the drug pharmacology. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Versatile antifouling polyethersulfone filtration membranes modified via surface grafting of zwitterionic polymers from a reactive amphiphilic copolymer additive.

    Science.gov (United States)

    Zhao, Yi-Fan; Zhang, Pei-Bin; Sun, Jian; Liu, Cui-Jing; Yi, Zhuan; Zhu, Li-Ping; Xu, You-Yi

    2015-06-15

    Here we describe the development of versatile antifouling polyethersulfone (PES) filtration membranes modified via surface grafting of zwitterionic polymers from a reactive amphiphilic copolymer additive. Amphiphilic polyethersulfone-block-poly(2-hydroxyethyl methacrylate) (PES-b-PHEMA) was beforehand designed and used as the blending additive of PES membranes prepared by phase inversion technique. The surface enriched PHEMA blocks on membrane surface acted as an anchor to immobilize the initiating site. Poly(sulfobetaine methacrylate) (PSBMA) were subsequently grafted onto the PES blend membranes by surface-initiated atom transfer radical polymerization (SI-ATRP). The analysis of surface chemistry confirmed the successful grafting of zwitterionic PSBMA brushes on PES membrane surface. The resulted PES-g-PSBMA membranes were capable of separating proteins from protein solution and oil from oil/water emulsion efficiently. Furthermore, the modified membranes showed high hydrophilicity and strongly antifouling properties due to the incorporation of well-defined PSBMA layer. In addition, the PES-g-PSBMA membranes exhibited excellent blood compatibility and durability during the washing process. The developed antifouling PES membranes are versatile and can find their applications in protein filtration, blood purification and oil/water separation, etc. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Two-dimensional crystallography of amphiphilic molecules at the air-water interface

    DEFF Research Database (Denmark)

    Jacquemain, D.; Grayer Wolf, S.; Leveiller, F.

    1992-01-01

    The advent of well-collimated, high-intensity synchrotron X-ray sources and the consequent development of surface-specific X-ray diffraction and fluorescence techniques have recently revolutionized the study of Langmuir monolayers at the air-liquid interface. These methods allowed for the first......, and review recent results obtained from them for Langmuir films. The methods have been successfully applied in the elucidation of the structure of crystalline aggregates of amphiphilic molecules such as alcohols, carboxylic acids and their salts, alpha-amino acids, and phospholipids at the water surface....... In addition, it became possible to monitor by diffraction the growth and dissolution of the crystalline self-aggregates as well as structural changes occurring by phase transitions. Furthermore, the surface X-ray methods shed new light on the structure of the underlying ionic layer of attached solvent...

  15. Relevance of the OCT1 transporter to the antineoplastic effect of biguanides

    International Nuclear Information System (INIS)

    Segal, Eric D.; Yasmeen, Amber; Beauchamp, Marie-Claude; Rosenblatt, Joshua; Pollak, Michael; Gotlieb, Walter H.

    2011-01-01

    Highlights: ► siRNA knockdown of OCT1 reduced sensitivity of EOC cells to metformin, but not to another biguanide, phenformin. ► Suppression of OCT1 also affects the activation of AMP kinase in response to metformin, but not to phenformin. ► Direct actions of metformin may be limited by low OCT1 expression in EOC tumors. ► Phenformin could be used as an alternative biguanide. -- Abstract: Epidemiologic and laboratory data suggesting that metformin has antineoplastic activity have led to ongoing clinical trials. However, pharmacokinetic issues that may influence metformin activity have not been studied in detail. The organic cation transporter 1 (OCT1) is known to play an important role in cellular uptake of metformin in the liver. We show that siRNA knockdown of OCT1 reduced sensitivity of epithelial ovarian cancer cells to metformin, but interestingly not to another biguanide, phenformin, with respect to both activation of AMP kinase and inhibition of proliferation. We observed that there is heterogeneity between primary human tumors with respect to OCT1 expression. These results suggest that there may be settings where drug uptake limits direct action of metformin on neoplastic cells, raising the possibility that metformin may not be the optimal biguanide for clinical investigation.

  16. Small angle neutron scattering study of the micelle structure of amphiphilic block copolymers

    International Nuclear Information System (INIS)

    Yamaoka, H.; Matsuoka, H.; Sumaru, K.; Hanada, S.

    1994-01-01

    The amphiphilic block copolymers of vinyl ether were prepared by living cationic polymerization. The partially deuterated copolymers for SANS experiments were especially synthesized by introducing deuterated phenyl units in the hydrophobic chain. SANS measurements were performed for aqueous solutions of these copolymers by changing H 2 O/D 2 O ratios. The SANS profiles indicate that the micelles in the present system exhibit a core-shell structure and that the size and shape of micelles are largely dependent on the length of hydrophobic chain. The micelle of shorter hydrophobic chain was found to be nearly spherical, whereas the micelle of longer hydrophobic chain was confirmed to have an ellipsoidal shape

  17. Ionization of amphiphilic acidic block copolymers.

    Science.gov (United States)

    Colombani, Olivier; Lejeune, Elise; Charbonneau, Céline; Chassenieux, Christophe; Nicolai, Taco

    2012-06-28

    The ionization behavior of an amphiphilic diblock copolymer poly(n-butyl acrylate(50%)-stat-acrylic acid(50%))(100)-block-poly(acrylic acid)(100) (P(nBA(50%)-stat-AA(50%))(100)-b-PAA(100), DH50) and of its equivalent triblock copolymer P(nBA(50%)-stat-AA(50%))(100)-b-PAA(200)-b-P(nBA(50%)-stat-AA(50%))(100) (TH50) were studied by potentiometric titration either in pure water or in 0.5 M NaCl. These polymers consist of a hydrophilic acidic block (PAA) connected to a hydrophobic block, P(nBA(50%)-stat-AA(50%))(100), whose hydrophobic character has been mitigated by copolymerization with hydrophilic units. We show that all AA units, even those in the hydrophobic block could be ionized. However, the AA units within the hydrophobic block were less acidic than those in the hydrophilic block, resulting in the preferential ionization of the latter block. The preferential ionization of PAA over that of P(nBA(50%)-stat-AA(50%))(100) was stronger at higher ionic strength. Remarkably, the covalent bonds between the PAA and P(nBA(50%)-stat-AA(50%))(100) blocks in the diblock or the triblock did not affect the ionization of each block, although the self-association of the block copolymers into spherical aggregates modified the environment of the PAA blocks compared to when PAA was molecularly dispersed.

  18. Interaction of amphiphilic drugs with human and bovine serum albumins.

    Science.gov (United States)

    Khan, Abbul Bashar; Khan, Javed Masood; Ali, Mohd Sajid; Khan, Rizwan Hasan; Kabir-Ud-Din

    2012-11-01

    To know the interaction of amphiphilic drugs nortriptyline hydrochloride (NOT) and promazine hydrochloride (PMZ) with serum albumins (i.e., human serum albumin (HSA) and bovine serum albumin (BSA)), techniques of UV-visible, fluorescence, and circular dichroism (CD) spectroscopies are used. The binding affinity is more in case of PMZ with both the serum albumins. The quenching rate constant (k(q)) values suggest a static quenching process for all the drug-serum albumin interactions. The UV-visible results show that the change in protein conformation of PMZ-serum albumin interactions are more prominent as compared to NOT-serum albumin interactions. The CD results also explain the conformational changes in the serum albumins on binding with the drugs. The increment in %α-helical structure is slightly more for drug-BSA complexes as compared to drug-HSA complexes. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. Synthesis and Characterization of Biodegradable Amphiphilic Star and Y-Shaped Block Copolymers as Potential Carriers for Vinorelbine

    Directory of Open Access Journals (Sweden)

    Fatemeh Bahadori

    2014-01-01

    Full Text Available Two amphiphilic block copolymers using hydrophobic poly(ε-caprolactone (PCL and hydrophilic poly(ethylene glycol (PEG were successfully synthesized. One of them is an (A-b-B4 type star polymer [(PCL-b-PEG4] and the other one is a Y-shaped PEG–(PCL2. A star-shaped polymer (PCL-b-PEG4 was prepared by ring-opening polymerization (ROP of ε-caprolactone continued by click reaction of (PCL-azide4 and PEG-alkyne. The synthesis of Y-shaped PEG–(PCL2 block copolymer was carried out via Diels-Alder click reaction of a furan protected maleimide end-functionalized PEG (PEG-MI with an anthracene end-functionalized PCL following the ROP of ε-caprolactone. The characterization of micelles is carried out using both materials in aqueous media as drug delivery vehicles, which showed satisfying results and enhanced the cytotoxic effect of the anti-cancer drug vinorelbine (VLB. However, micelles consisted of Y-shaped unimers were found to be more convenient for delivery of hydrophobic drugs such as VLB because they formed in lower concentration, carrying a higher amount of drugs and owing a monomodal distribution. We concluded that the free tails of hydrophobic chains in Y-shaped block copolymer facilitate the assembly of amphiphilic material in water to form micelles.

  20. Structural and functional determinants of conserved lipid interaction domains of inward rectifying Kir6.2 channels.

    Science.gov (United States)

    Cukras, Catherine A; Jeliazkova, Iana; Nichols, Colin G

    2002-06-01

    All members of the inward rectifiier K(+) (Kir) channel family are activated by phosphoinositides and other amphiphilic lipids. To further elucidate the mechanistic basis, we examined the membrane association of Kir6.2 fragments of K(ATP) channels, and the effects of site-directed mutations of these fragments and full-length Kir6.2 on membrane association and K(ATP) channel activity, respectively. GFP-tagged Kir6.2 COOH terminus and GFP-tagged pleckstrin homology domain from phospholipase C delta1 both associate with isolated membranes, and association of each is specifically reduced by muscarinic m1 receptor-mediated phospholipid depletion. Kir COOH termini are predicted to contain multiple beta-strands and a conserved alpha-helix (residues approximately 306-311 in Kir6.2). Systematic mutagenesis of D307-F315 reveals a critical role of E308, I309, W311 and F315, consistent with residues lying on one side of a alpha-helix. Together with systematic mutation of conserved charges, the results define critical determinants of a conserved domain that underlies phospholipid interaction in Kir channels.

  1. Synthesis of Novel Amphiphilic Azobenzenes and X-ray Scattering Studies of Their Langmuir Monolayers

    DEFF Research Database (Denmark)

    Sørensen, Thomas Just; Kjær, Kristian; Breiby, Dag Werner

    2008-01-01

    . At the air-water interface, the amphiphilic azobenzenes form noncrystalline but stable Langmuir films that display an unusual reversible monolayer collapse close to 35 mN/m. The structures and phase transitions were studied by X-ray reflectivity (XR) and grazing-incidence X-ray diffraction, both utilizing...... synchrotron radiation. Compression beyond the collapse point does not change the XR data, showing that the film is unchanged at the molecular level, even at areas less than half of that of the collapse. This leads to the conclusion that few macroscopic collapse sites are responsible for reversibly removing...

  2. Gold Nanoparticles Protected with Thiol-Derivatized Amphiphilic Poly(epsilon-caprolactone)-b-poly(acrylic acid)

    DEFF Research Database (Denmark)

    Javakhishvili, Irakli; Hvilsted, Søren

    2009-01-01

    ) of tent-butyl acrylate (tBA) in a controlled fashion by use of NiBr2(PPh3)(2) catalyst to produce Prot-PCL-b-PtBA with narrow polydispersities (1.17-1.39). Subsequent mild deprotection protocols provided HS-PCL-b-PAA. Reduction of a gold salt in the presence of this macroligand under thiol......Amphiphilic poly(epsilon-caprolactone)-b-poly(acrylic acid) (HS-PCL-b-PAA) with a thiol functionality in the PCL terminal has been prepared in a novel synthetic cascade. Initially, living anionic ring-opening polymerization (ROP) of epsilon-caprolactone (epsilon-CL) employing the difunctional...

  3. Tailorable Exciton Transport in Doped Peptide–Amphiphile Assemblies

    Energy Technology Data Exchange (ETDEWEB)

    Solomon, Lee A. [Center; Sykes, Matthew E. [Center; Wu, Yimin A. [Center; Schaller, Richard D. [Center; Department; Wiederrecht, Gary P. [Center; Fry, H. Christopher [Center

    2017-08-29

    Light-harvesting biomaterials are an attractive target in photovoltaics, photocatalysis, and artificial photosynthesis. Through peptide self-assembly, complex nanostructures can be engineered to study the role of chromophore organization during light absorption and energy transport. To this end, we demonstrate the one-dimensional transport of excitons along naturally occurring, light-harvesting, Zn-protoporphyrin IX chromophores within self-assembled peptide-amphiphile nanofibers. The internal structure of the nanofibers induces packing of the porphyrins into linear chains. We find that this peptide assembly can enable long-range exciton diffusion, yet it also induces the formation of excimers between adjacent molecules, which serve as exciton traps. Electronic coupling between neighboring porphyrin molecules is confirmed by various spectroscopic methods. The exciton diffusion process is then probed through transient photoluminescence and absorption measurements and fit to a model for one-dimensional hopping. Because excimer formation impedes exciton hopping, increasing the interchromophore spacing allows for improved diffusivity, which we control through porphyrin doping levels. We show that diffusion lengths of over 60 nm are possible at low porphyrin doping, representing an order of magnitude improvement over the highest doping fractions.

  4. Yolk–shell Fe3O4@SiO2@PMO: amphiphilic magnetic nanocomposites as an adsorbent and a catalyst with high efficiency and recyclability

    KAUST Repository

    Dai, Jinyu; Zou, Houbing; Wang, Runwei; Wang, Yu; Shi, Zhiqiang; Qiu, Shilun

    2017-01-01

    This study describes the preparation of a multifunctional adsorptive catalyst by the incorporation of ligand groups within the channels of magnetic amphiphilic nanocomposites and attached with Pd nanoparticles. It was clearly demonstrated that Pd2

  5. A novel ionic amphiphilic chitosan derivative as a stabilizer of nanoemulsions: Improvement of antimicrobial activity of Cymbopogon citratus essential oil.

    Science.gov (United States)

    Bonferoni, Maria Cristina; Sandri, Giuseppina; Rossi, Silvia; Usai, Donatella; Liakos, Ioannis; Garzoni, Alice; Fiamma, Maura; Zanetti, Stefania; Athanassiou, Athanassia; Caramella, Carla; Ferrari, Franca

    2017-04-01

    Amphiphilic chitosans have been recently proposed to improve delivery of poorly soluble drugs. In the present paper a derivative obtained by ionic interaction between chitosan and oleic acid was for the first time studied to physically stabilize o/w nanoemulsions of an antimicrobial essential oil, Cymbopogon citratus (Lemongrass), in a low energy and mild conditions emulsification process. The novel combination of spontaneous emulsification process with chitosan oleate amphiphilic properties resulted in a stable dispersion of a few hundred nanometer droplets. Positive zeta potential confirmed the presence of a chitosan shell around the oil droplets, which is responsible for the nanoemulsion physical stabilization and for the maintenance of chitosan bioactive properties, such as mucoadhesion. Cytotoxicity test was performed on four different cell lines (HEp-2, Caco-2, WKD and McCoy cells) showing biocompatibility of the system. The maintenance and in some cases even a clear improvement in the essential oil antimicrobial activity towards nine bacterial and ten fungal strains, all of clinical relevance was verified for Lemongrass nanoemulsion. Copyright © 2017. Published by Elsevier B.V.

  6. An amphiphilic graft copolymer-based nanoparticle platform for reduction-responsive anticancer and antimalarial drug delivery

    Science.gov (United States)

    Najer, Adrian; Wu, Dalin; Nussbaumer, Martin G.; Schwertz, Geoffrey; Schwab, Anatol; Witschel, Matthias C.; Schäfer, Anja; Diederich, François; Rottmann, Matthias; Palivan, Cornelia G.; Beck, Hans-Peter; Meier, Wolfgang

    2016-08-01

    Medical applications of anticancer and antimalarial drugs often suffer from low aqueous solubility, high systemic toxicity, and metabolic instability. Smart nanocarrier-based drug delivery systems provide means of solving these problems at once. Herein, we present such a smart nanoparticle platform based on self-assembled, reduction-responsive amphiphilic graft copolymers, which were successfully synthesized through thiol-disulfide exchange reaction between thiolated hydrophilic block and pyridyl disulfide functionalized hydrophobic block. These amphiphilic graft copolymers self-assembled into nanoparticles with mean diameters of about 30-50 nm and readily incorporated hydrophobic guest molecules. Fluorescence correlation spectroscopy (FCS) was used to study nanoparticle stability and triggered release of a model compound in detail. Long-term colloidal stability and model compound retention within the nanoparticles was found when analyzed in cell media at body temperature. In contrast, rapid, complete reduction-triggered disassembly and model compound release was achieved within a physiological reducing environment. The synthesized copolymers revealed no intrinsic cellular toxicity up to 1 mg mL-1. Drug-loaded reduction-sensitive nanoparticles delivered a hydrophobic model anticancer drug (doxorubicin, DOX) to cancer cells (HeLa cells) and an experimental, metabolically unstable antimalarial drug (the serine hydroxymethyltransferase (SHMT) inhibitor (+/-)-1) to Plasmodium falciparum-infected red blood cells (iRBCs), with higher efficacy compared to similar, non-sensitive drug-loaded nanoparticles. These responsive copolymer-based nanoparticles represent a promising candidate as smart nanocarrier platform for various drugs to be applied to different diseases, due to the biocompatibility and biodegradability of the hydrophobic block, and the protein-repellent hydrophilic block.Medical applications of anticancer and antimalarial drugs often suffer from low aqueous

  7. Uncaria tomentosa exerts extensive anti-neoplastic effects against the Walker-256 tumour by modulating oxidative stress and not by alkaloid activity.

    Directory of Open Access Journals (Sweden)

    Arturo Alejandro Dreifuss

    Full Text Available This study aimed to compare the anti-neoplastic effects of an Uncaria tomentosa (UT brute hydroethanolic (BHE extract with those of two fractions derived from it. These fractions are choroformic (CHCl3 and n-butanolic (BuOH, rich in pentacyclic oxindole alkaloids (POA and antioxidant substances, respectively. The cancer model was the subcutaneous inoculation of Walker-256 tumour cells in the pelvic limb of male Wistar rat. Subsequently to the inoculation, gavage with BHE extract (50 mg.kg(-1 or its fractions (as per the yield of the fractioning process or vehicle (Control was performed during 14 days. Baseline values, corresponding to individuals without tumour or treatment with UT, were also included. After treatment, tumour volume and mass, plasma biochemistry, oxidative stress in liver and tumour, TNF-α level in liver and tumour homogenates, and survival rates were analysed. Both the BHE extract and its BuOH fraction successfully reduced tumour weight and volume, and modulated anti-oxidant systems. The hepatic TNF-α level indicated a greater effect from the BHE extract as compared to its BuOH fraction. Importantly, both the BHE extract and its BuOH fraction increased the survival time of the tumour-bearing animals. Inversely, the CHCl3 fraction was ineffective. These data represent an in vivo demonstration of the importance of the modulation of oxidative stress as part of the anti-neoplastic activity of UT, as well as constitute evidence of the lack of activity of isolated POAs in the primary tumour of this tumour lineage. These effects are possibly resulting from a synergic combination of substances, most of them with antioxidant properties.

  8. Lipid Cell Biology: A Focus on Lipids in Cell Division.

    Science.gov (United States)

    Storck, Elisabeth M; Özbalci, Cagakan; Eggert, Ulrike S

    2018-06-20

    Cells depend on hugely diverse lipidomes for many functions. The actions and structural integrity of the plasma membrane and most organelles also critically depend on membranes and their lipid components. Despite the biological importance of lipids, our understanding of lipid engagement, especially the roles of lipid hydrophobic alkyl side chains, in key cellular processes is still developing. Emerging research has begun to dissect the importance of lipids in intricate events such as cell division. This review discusses how these structurally diverse biomolecules are spatially and temporally regulated during cell division, with a focus on cytokinesis. We analyze how lipids facilitate changes in cellular morphology during division and how they participate in key signaling events. We identify which cytokinesis proteins are associated with membranes, suggesting lipid interactions. More broadly, we highlight key unaddressed questions in lipid cell biology and techniques, including mass spectrometry, advanced imaging, and chemical biology, which will help us gain insights into the functional roles of lipids.

  9. Template-Assisted Benzannulation Route to Pentacene and Tetracene Derivatives and its Application to Construct Amphiphilic Acenes That Self-Assemble into Helical Wires.

    Science.gov (United States)

    Pal, Bikash; Chang, Chun-Hsiung; Zeng, Cian-Jhe; Lin, Chih-Hsiu

    2017-12-11

    Pentacene is one of the most versatile organic semiconductors. New synthetic strategies to construct the pentacene skeleton are imperative to produce pentacene derivatives with appropriate solubility, stability, and optoelectronic properties for various applications. This paper describes a template-directed approach to pentacene derivatives. In the retrosynthesis, the acene skeleton is viewed as a laddered double strand polyene instead of the more intuitive linearly fused hexagons. Based on this vision, the template strand of polyene is constructed with Wittig olefination, whereas the second strand is accomplished with Knoevenagel condensation to produce pentacene and tetracene derivatives. The synthetic scheme is flexible enough to generate an array of acene derivatives with substitution patterns that were hitherto difficult to access. Amphiphilic pentacene and tetracene derivatives were also synthesized by the template strategy. One pentacene based amphiphilic rod-coil molecule undergoes self-assembly to form helical wire structures that were visualized with TEM. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Amphiphilic conjunct of methyl cellulose and well-defined polyvinyl acetate.

    Science.gov (United States)

    Xiao, Congming; Xia, Cunping

    2013-01-01

    Tailor-made conjunct of methyl cellulose (MC) and polyvinyl acetate (PVAc) was synthesized through the combination of reversible addition-fragmentation chain transfer (RAFT) polymerization and thiol-ene click reaction. MC was firstly transferred into unsaturated MC (UMC), and then covalently connected with well-defined PVAc obtained by RAFT polymerization of vinyl acetate. The structure of the conjunct polymer (MCV) was confirmed with Fourier transform infrared spectra (FTIR) and proton nuclear magnetic resonance ((1)H NMR). Well-defined MCV was amphiphilic and able to self-assemble into size controllable micelles, which was verified with transmission electron microscopy (TEM) and size distribution analysis. It was found that the mean diameters of the micelles in aqueous solution were 105.6, 96.0 and 75.9 nm when the number average molecular weights of PVAc segments of MCV were 49,300, 32,500 and 18,200, respectively. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. Amphiphilic Quantum Dots with Asymmetric, Mixed Polymer Brush Layers: From Single Core-Shell Nanoparticles to Salt-Induced Vesicle Formation

    Directory of Open Access Journals (Sweden)

    Brian R. Coleman

    2018-03-01

    Full Text Available A mixed micelle approach is used to produce amphiphilic brush nanoparticles (ABNPs with cadmium sulfide quantum dot (QD cores and surface layers of densely grafted (σ = ~1 chain/nm2 and asymmetric (fPS = 0.9 mixed polymer brushes that contain hydrophobic polystyrene (PS and hydrophilic poly(methyl methacrylate (PMAA chains (PS/PMAA-CdS. In aqueous media, the mixed brushes undergo conformational rearrangements that depend strongly on prior salt addition, giving rise to one of two pathways to fluorescent and morphologically disparate QD-polymer colloids. (A In the absence of salt, centrosymmetric condensation of PS chains forms individual core-shell QD-polymer colloids. (B In the presence of salt, non-centrosymmetric condensation of PS chains forms Janus particles, which trigger anisotropic interactions and amphiphilic self-assembly into the QD-polymer vesicles. To our knowledge, this is the first example of an ABNP building block that can form either discrete core-shell colloids or self-assembled superstructures in water depending on simple changes to the chemical conditions (i.e., salt addition. Such dramatic and finely tuned morphological variation could inform numerous applications in sensing, biolabeling, photonics, and nanomedicine.

  12. Mesoporous tertiary oxides via a novel amphiphilic approach

    Energy Technology Data Exchange (ETDEWEB)

    Bennett, Natasha; Hall, Simon R., E-mail: simon.hall@bristol.ac.uk, E-mail: Annela.Seddon@bristol.ac.uk [Bristol Centre for Functional Nanomaterials, Centre for Nanoscience and Quantum Information, Tyndall Avenue, Bristol BS8 1FD, United Kingdom and Complex Functional Materials Group, School of Chemistry, University of Bristol, Bristol BS8 1TS (United Kingdom); Seddon, Annela M., E-mail: simon.hall@bristol.ac.uk, E-mail: Annela.Seddon@bristol.ac.uk; Hallett, James E. [H.H. Wills Physics Laboratory, University of Bristol, Tyndall Avenue, Bristol BS8 1TL (United Kingdom); Kockelmann, Winfried [STFC Rutherford Appleton Laboratory, Chilton OX11 0QX (United Kingdom); Ting, Valeska P. [Department of Chemical Engineering, University of Bath, Bath BA2 7AY (United Kingdom); Sadasivan, Sajanikumari; Tooze, Robert P. [Sasol Technology (UK) Ltd, Purdie Building, North Haugh, St Andrews, Fife KY16 9ST (United Kingdom)

    2016-01-01

    We report a facile biomimetic sol-gel synthesis using the sponge phase formed by the lipid monoolein as a structure-directing template, resulting in high phase purity, mesoporous dysprosium- and gadolinium titanates. The stability of monoolein in a 1,4-butanediol and water mixture complements the use of a simple sol-gel metal oxide synthesis route. By judicious control of the lipid/solvent concentration, the sponge phase of monoolein can be directly realised in the pyrochlore material, leading to a porous metal oxide network with an average pore diameter of 10 nm.

  13. Gold Nanoparticles Protected with Thiol-Derivatized Amphiphilic Poly( -caprolactone)-b-poly(acrylic acid)

    DEFF Research Database (Denmark)

    Javakhishvili, Irakli; Hvilsted, Søren

    2008-01-01

    Amphiphilic poly(c-caprolactone)-b-poly(acrylic acid) (HS-PCL-b-PAA) bearing thiol functionality at the PCL terminal has been synthesized by a combination of ring-opening polymerization (ROP) of c-caprolactone (c-CL), esterification of hydroxy chain end with protected mercaptoacetic acid, subsequ....... As a result stable, aggregation-free nanopaticles with moderate dispersity as estimated from UV-visible spectroscopy and transmission electron microscopy (TEM) data were obtained....... chromatography (SEC), nuclear magnetic resonance eR NMR) and infrared (FT IR) spectroscopy. The capacity of the resulting block copolymer in preparation of monolayer-protected gold nanoparticles has been examined by reduction of a gold salt in the presence of this macroligand under thiol-deficient conditions...

  14. Novel N,N '-diacyl-1,3-diaminopropyl-2-carbamoyl bivalent cationic lipids for gene delivery--synthesis, in vitro transfection activity, and physicochemical characterization.

    Science.gov (United States)

    Spelios, Michael; Savva, Michalakis

    2008-01-01

    Novel N,N'-diacyl-1,3-diaminopropyl-2-carbamoyl bivalent cationic lipids were synthesized and their physicochemical properties in lamellar assemblies with and without plasmid DNA were evaluated to elucidate the structural requirements of these double-chained pH-sensitive surfactants for potent non-viral gene delivery and expression. The highest in vitro transfection efficacies were induced at +/-4:1 by the dimyristoyl, dipalmitoyl and dioleoyl derivatives 1,3lb2, 1,3lb3 and 1,3lb5, respectively, without inclusion of helper lipids. Transfection activities were reduced in the presence of either 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine alone or in combination with cholesterol for all derivatives except 1,3lb5, which maintained reporter gene expression levels at +/-4:1 and yielded increased lipofection activity at a lower charge ratio of +/-2:1. Ethidium bromide displacement indicated efficient plasmid DNA binding and compaction by the transfection-competent analogs. Dynamic light-scattering and electrophoretic mobility studies revealed lipoplexes of the active lipids with large particle sizes (mean diameter>or=500 nm) and zeta potentials with positive values (low ionic strength) or below neutrality (high ionic strength). Langmuir film balance studies showed high in-plane elasticity of these derivatives in isolation. In agreement with the monolayer experiments, fluorescence polarization studies verified the fluid nature of the highly transfection-efficient amphiphiles, with gel-to-liquid crystalline phase transitions below physiological temperature. The active compounds also interacted with endosome-mimicking vesicles to a greater extent than the poorly active derivative 1,3lb4, as revealed by fluorescence resonance energy transfer experiments. Taken together, the results suggest that well-hydrated and highly elastic cationic lipids with increased acyl chain fluidity and minimal cytotoxicity elicit high transfection activity.

  15. Amphiphilic block copolymers for drug delivery.

    Science.gov (United States)

    Adams, Monica L; Lavasanifar, Afsaneh; Kwon, Glen S

    2003-07-01

    Amphiphilic block copolymers (ABCs) have been used extensively in pharmaceutical applications ranging from sustained-release technologies to gene delivery. The utility of ABCs for delivery of therapeutic agents results from their unique chemical composition, which is characterized by a hydrophilic block that is chemically tethered to a hydrophobic block. In aqueous solution, polymeric micelles are formed via the association of ABCs into nanoscopic core/shell structures at or above the critical micelle concentration. Upon micellization, the hydrophobic core regions serve as reservoirs for hydrophobic drugs, which may be loaded by chemical, physical, or electrostatic means, depending on the specific functionalities of the core-forming block and the solubilizate. Although the Pluronics, composed of poly(ethylene oxide)-block-poly(propylene oxide)-block-poly(ethylene oxide), are the most widely studied ABC system, copolymers containing poly(L-amino acid) and poly(ester) hydrophobic blocks have also shown great promise in delivery applications. Because each ABC has unique advantages with respect to drug delivery, it may be possible to choose appropriate block copolymers for specific purposes, such as prolonging circulation time, introduction of targeting moieties, and modification of the drug-release profile. ABCs have been used for numerous pharmaceutical applications including drug solubilization/stabilization, alteration of the pharmacokinetic profile of encapsulated substances, and suppression of multidrug resistance. The purpose of this minireview is to provide a concise, yet detailed, introduction to the use of ABCs and polymeric micelles as delivery agents as well as to highlight current and past work in this area. Copyright 2003 Wiley-Liss, Inc. and the American Pharmacists Association

  16. Lipid Structure in Triolein Lipid Droplets

    DEFF Research Database (Denmark)

    Chaban, Vitaly V; Khandelia, Himanshu

    2014-01-01

    of a mass of hydrophobic lipid esters coved by phospholipid monolayer. The small size and unique architecture of LDs makes it complicated to study LD structure by modern experimental methods. We discuss coarse-grained molecular dynamics (MD) simulations of LD formation in systems containing 1-palmitoyl-2...... to coarse-grained simulations, the presence of PE lipids at the interface has a little impact on distribution of components and on the overall LD structure. (4) The thickness of the lipid monolayer at the surface of the droplet is similar to the thickness of one leaflet of a bilayer. Computer simulations......Lipid droplets (LDs) are primary repositories of esterified fatty acids and sterols in animal cells. These organelles originate on the lumenal or cytoplasmic side of endoplasmic reticulum (ER) membrane and are released to the cytosol. In contrast to other intracellular organelles, LDs are composed...

  17. Concanavalin A: A potential anti-neoplastic agent targeting apoptosis, autophagy and anti-angiogenesis for cancer therapeutics

    International Nuclear Information System (INIS)

    Li, Wen-wen; Yu, Jia-ying; Xu, Huai-long; Bao, Jin-ku

    2011-01-01

    Highlights: → ConA induces cancer cell death targeting apoptosis and autophagy. → ConA inhibits cancer cell angiogenesis. → ConA is utilized in pre-clinical and clinical trials. -- Abstract: Concanavalin A (ConA), a Ca 2+ /Mn 2+ -dependent and mannose/glucose-binding legume lectin, has drawn a rising attention for its remarkable anti-proliferative and anti-tumor activities to a variety of cancer cells. ConA induces programmed cell death via mitochondria-mediated, P73-Foxo1a-Bim apoptosis and BNIP3-mediated mitochondrial autophagy. Through IKK-NF-κB-COX-2, SHP-2-MEK-1-ERK, and SHP-2-Ras-ERK anti-angiogenic pathways, ConA would inhibit cancer cell survival. In addition, ConA stimulates cell immunity and generates an immune memory, resisting to the same genotypic tumor. These biological findings shed light on new perspectives of ConA as a potential anti-neoplastic agent targeting apoptosis, autophagy and anti-angiogenesis in pre-clinical or clinical trials for cancer therapeutics.

  18. Non-electrostatic complexes with DNA: towards novel synthetic gene delivery systems.

    Science.gov (United States)

    Soto, J; Bessodes, M; Pitard, B; Mailhe, P; Scherman, D; Byk, G

    2000-05-01

    We have developed new DNA complexing amphiphile based on Hoechst 33258 interaction with DNA grooves. The synthesis and physicochemical characterisation of lipid/DNA complexes, as compared to that of classical lipopolyamine for gene delivery, are described and discussed.

  19. Relevance of the OCT1 transporter to the antineoplastic effect of biguanides

    Energy Technology Data Exchange (ETDEWEB)

    Segal, Eric D.; Yasmeen, Amber; Beauchamp, Marie-Claude; Rosenblatt, Joshua [Division of Gynecologic Oncology, Jewish General Hospital, McGill University, Montreal, Quebec (Canada); Segal Cancer Center, Lady Davis Institute of Medical Research, McGill University, Montreal, Quebec (Canada); Pollak, Michael [Segal Cancer Center, Lady Davis Institute of Medical Research, McGill University, Montreal, Quebec (Canada); Department of Oncology, McGill University, Montreal, Quebec (Canada); Gotlieb, Walter H., E-mail: walter.gotlieb@mcgill.ca [Division of Gynecologic Oncology, Jewish General Hospital, McGill University, Montreal, Quebec (Canada); Segal Cancer Center, Lady Davis Institute of Medical Research, McGill University, Montreal, Quebec (Canada); Department of Oncology, McGill University, Montreal, Quebec (Canada)

    2011-11-04

    Highlights: Black-Right-Pointing-Pointer siRNA knockdown of OCT1 reduced sensitivity of EOC cells to metformin, but not to another biguanide, phenformin. Black-Right-Pointing-Pointer Suppression of OCT1 also affects the activation of AMP kinase in response to metformin, but not to phenformin. Black-Right-Pointing-Pointer Direct actions of metformin may be limited by low OCT1 expression in EOC tumors. Black-Right-Pointing-Pointer Phenformin could be used as an alternative biguanide. -- Abstract: Epidemiologic and laboratory data suggesting that metformin has antineoplastic activity have led to ongoing clinical trials. However, pharmacokinetic issues that may influence metformin activity have not been studied in detail. The organic cation transporter 1 (OCT1) is known to play an important role in cellular uptake of metformin in the liver. We show that siRNA knockdown of OCT1 reduced sensitivity of epithelial ovarian cancer cells to metformin, but interestingly not to another biguanide, phenformin, with respect to both activation of AMP kinase and inhibition of proliferation. We observed that there is heterogeneity between primary human tumors with respect to OCT1 expression. These results suggest that there may be settings where drug uptake limits direct action of metformin on neoplastic cells, raising the possibility that metformin may not be the optimal biguanide for clinical investigation.

  20. Fabrication of platinum nanoparticles in aqueous solution and solid phase using amphiphilic PB-b-PEO copolymer nanoreactors

    International Nuclear Information System (INIS)

    Hoda, Numan; Budama, Leyla; Çakır, Burçin Acar; Topel, Önder; Ozisik, Rahmi

    2013-01-01

    Graphical abstract: TEM image of Pt nanoparticles produced by reducing by NaBH 4 within PB-b-PEO micelles in aqueous media (scale bar 1 nm). - Highlights: • Pt nanoparticles were synthesized within amphiphilic diblock copolymer micelles. • The effects of reducing agents and precursor dose on Pt np size were investigated. • The effect on fabrication of Pt np by reducing in aqueous and solid phases was compared. • The size of nanoparticles was about 1.4 nm for all doses and reducing agents types. - Abstract: Fabrication of Pt nanoparticles using an amphiphilic copolymer template in aqueous solution was achieved via polybutadiene-block-polyethyleneoxide copolymer micelles, which acted as nanoreactors. In addition, Pt nanoparticles were synthesized using hydrogen gas as the reducing agent in solid state for the first time to compare against solution synthesis. The influences of loaded precursor salt amount to micelles and the type of reducing agent on the size of nanoparticles were investigated through transmission electron microscopy. It was found that increasing the ratio of precursor salt to copolymer and using different type of reducing agent, even in solid phase reduction, did not affect the nanoparticle size. The average size of Pt nanoparticles was estimated to be 1.4 ± 0.1 nm. The reason for getting same sized nanoparticles was discussed in the light of nucleation, growth process, stabilization and diffusion of nanoparticles within micelles

  1. Self-Delivery Nanoparticles of Amphiphilic Methotrexate-Gemcitabine Prodrug for Synergistic Combination Chemotherapy via Effect of Deoxyribonucleotide Pools.

    Science.gov (United States)

    Wang, Yao; Huang, Ping; Hu, Minxi; Huang, Wei; Zhu, Xinyuan; Yan, Deyue

    2016-11-16

    The distinct and complementary biochemical mechanisms of folic acid analog methotrexate (MTX) and cytidine analog gemcitabine (GEM) make their synergistic combination effective. Unfortunately, such a combination faces severe pharmacokinetic problems and several transportation barriers. To overcome these problems, a new strategy of amphiphilic small molecule prodrug (ASMP) is developed to improve their synergistic combination effect. The ASMP was prepared by the amidation of the hydrophilic GEM with the hydrophobic MTX at a fixed ratio. Owing to its inherent amphiphilicity, the MTX-GEM ASMP self-assembled into stable nanoparticles (ASMP-NPs) with high drug loading capacity (100%), in which the MTX and GEM could self-deliver without any carriers and release synchronously in cancer cells. In vitro studies showed that the MTX-GEM ASMP-NPs could greatly improve the synergistic combination effects by the reason of arresting more S phase of the cell cycle and reducing levels of deoxythymidine triphosphate (dTTP), deoxyadenosine triphosphate (dATP), and deoxycytidine triphosphate (dCTP). The stronger synergistic effects caused the higher cell cytotoxicity and apoptotic ratio, and circumvented the multidrug resistance (MDR) of tumor cells. Additionally, MTX-GEM ASMP-NPs could achieve the same anticancer effect with the greatly reduced dosage compared with the free drugs according to the dose-reduction index (DRI) values of MTX and GEM in MTX-GEM ASMP-NPs, which may be beneficial for reducing the side effects.

  2. Analysis of lipid profile in lipid storage myopathy.

    Science.gov (United States)

    Aguennouz, M'hammed; Beccaria, Marco; Purcaro, Giorgia; Oteri, Marianna; Micalizzi, Giuseppe; Musumesci, Olimpia; Ciranni, Annmaria; Di Giorgio, Rosa Maria; Toscano, Antonio; Dugo, Paola; Mondello, Luigi

    2016-09-01

    Lipid dysmetabolism disease is a condition in which lipids are stored abnormally in organs and tissues throughout the body, causing muscle weakness (myopathy). Usually, the diagnosis of this disease and its characterization goes through dosage of Acyl CoA in plasma accompanied with evidence of droplets of intra-fibrils lipids in the patient muscle biopsy. However, to understand the pathophysiological mechanisms of lipid storage diseases, it is useful to identify the nature of lipids deposited in muscle fiber. In this work fatty acids and triglycerides profile of lipid accumulated in the muscle of people suffering from myopathies syndromes was characterized. In particular, the analyses were carried out on the muscle biopsy of people afflicted by lipid storage myopathy, such as multiple acyl-coenzyme A dehydrogenase deficiency, and neutral lipid storage disease with myopathy, and by the intramitochondrial lipid storage dysfunctions, such as deficiencies of carnitine palmitoyltransferase II enzyme. A single step extraction and derivatization procedure was applied to analyze fatty acids from muscle tissues by gas chromatography with a flame ionization detector and with an electronic impact mass spectrometer. Triglycerides, extracted by using n-hexane, were analyzed by high performance liquid chromatography coupled to mass spectrometer equipped with an atmospheric pressure chemical ionization interface. The most representative fatty acids in all samples were: C16:0 in the 13-24% range, C18:1n9 in the 20-52% range, and C18:2n6 in the 10-25% range. These fatty acids were part of the most representative triglycerides in all samples. The data obtained was statistically elaborated performing a principal component analysis. A satisfactory discrimination was obtained among the different diseases. Using component 1 vs component 3 a 43.3% of total variance was explained. Such results suggest the important role that lipid profile characterization can have in supporting a correct

  3. Self-Assembly of Calix[4]arene-Based Amphiphiles Bearing Polyethylene Glycols: Another Example of "Platonic Micelles".

    Science.gov (United States)

    Yoshida, Kenta; Fujii, Shota; Takahashi, Rintaro; Matsumoto, Sakiko; Sakurai, Kazuo

    2017-09-12

    The aggregation number of classical micelles exhibits a certain distribution, which is a recognizable feature of conventional micelles. However, we recently identified perfectly monodisperse calix[4]arene-based micelles whose aggregation numbers agree with the vertex numbers of regular polyhedra, that is, Platonic solids, and thus they are named "Platonic micelles". Regarding our hypothesis of the formation mechanism of Platonic micelles, both repulsive interactions including steric hindrance and electrostatic repulsions among the headgroups are important for determining their aggregation number; however, neither of these is necessarily needed to consider. In this study, we employed polyethylene glycols (PEGs) as the nonionic headgroup of calix[4]arene-based amphiphiles to study the effects of only repulsive interactions caused by steric hindrance on the formation of Platonic micelles. The amphiphiles containing relatively low-molecular-weight PEGs (550 or 1000 g mol -1 ) form dodecamer or octamer micelles, respectively, with no variation in the aggregation number. However, relatively high-molecular-weight PEGs (2000 g mol -1 ) produce polydispersed micelles with a range of aggregation number. PEG 2000 exhibits a greater affinity for water than PEG 550 and 1000, resulting in fewer hydrophobic interactions in micelle formation, as indicated by the drastic increase of the critical micelle concentration (CMC) value in the PEG 2000 system. The instability of the structure of PEG 2k CaL5 micelles might contribute to the higher mobility of PEG in the micellar shell, resulting in a non-Platonic aggregation number with polydispersity.

  4. Important exposure controls for protection against antineoplastic agents: Highlights for oncology health care workers.

    Science.gov (United States)

    Alehashem, Maryam; Baniasadi, Shadi

    2018-01-01

    A great number of antineoplastic drugs (ANPDs) are used globally in cancer treatment. Due to their adverse health effects, occupational exposure to ANPDs is considered a potential health risk to health care workers. The current study aimed to evaluate safe-handling practices of ANPDs, exposure controls, and adverse health implications for health care providers exposed to ANDPs. Prevention measures, including engineering, administrative, and work practice controls, as well as personal protective equipment (PPE), were recorded daily through a questionnaire for six weeks. Acute adverse health effects experienced by health care workers were also documented. The implemented exposure controls for preparation, administration, cleaning, and waste disposal were not in accordance with the safe handling guidelines. Central nervous system disorders (26.33%) were the most frequent acute adverse effects reported by health care workers. A significant correlation was found between the number of experienced adverse effects and handling characteristics, including the number of preparations (r = 0.38, p health care workers were in danger of exposure to ANPDs and experienced acute adverse health effects. Implementation of appropriate exposure controls is required to prevent occupational exposure to ANPDs.

  5. Sesquiterpene lactones: Mechanism of antineoplastic activity; relationship of cellular glutathione to cytotoxicity; and disposition

    International Nuclear Information System (INIS)

    Grippo, A.A.

    1987-01-01

    Helenalin, a sesquiterpene lactone, inhibited the growth of P388 lymphocytic and L1210 lymphoid leukemia, and Ehrlich ascites and KB carcinoma cells. The L1210 leukemia cells were most sensitive to the cytotoxic effects of helenalin. Helenalin's antineoplastic effects were due to inhibition of DNA synthesis by suppressing the activities of enzymes involved in this biosynthetic pathway; i.e., IMP dehydrogenase, ribonucleoside diphosphate reductase, thioredoxin complex, GSH disulfide oxidoreductase and DNA polymerase α activities. The relationship of reduced glutathione (GSH) to the cytotoxic effects of helanalin was evaluated. L1210 cells, which were more sensitive to helenalin's toxicity, contained lower basal concentrations of GSH. Helenalin decreased the concentration of reduced glutathione in both L1210 and P388 leukemia cells. Concurrent administration of helanalin with agents reported to raise GSH concentrations did not substantially effect GSH levels, nor were survival times of tumor-bearing mice enhanced. Following intraperitoneal administration of 3 H-plenolin, no radioactive drug and/or metabolite was sequestered in the organs of BDF 1 mice. Approximately 50% of 3 H-plenolin and/or its metabolites were eliminated via urine while lesser amounts of radioactive drug and/or metabolites were eliminated in the feces

  6. Stability of asymmetric lipid bilayers assessed by molecular dynamics simulations

    NARCIS (Netherlands)

    Esteban-Martin, Santi; Risselada, H. Jelger; Salgado, Jesus; Marrink, Siewert J.

    2009-01-01

    The asymmetric insertion of amphiphiles into biological membranes compromises the balance between the inner and outer monolayers. As a result, area expansion of the receiving leaflet and curvature strain may lead to membrane permeation, shape changes, or membrane fusion events. We have conducted

  7. Chemical and structural investigation of lipid nanoparticles: drug-lipid interaction and molecular distribution

    Science.gov (United States)

    Anantachaisilp, Suranan; Meejoo Smith, Siwaporn; Treetong, Alongkot; Pratontep, Sirapat; Puttipipatkhachorn, Satit; Rungsardthong Ruktanonchai, Uracha

    2010-03-01

    Lipid nanoparticles are a promising alternative to existing carriers in chemical or drug delivery systems. A key challenge is to determine how chemicals are incorporated and distributed inside nanoparticles, which assists in controlling chemical retention and release characteristics. This study reports the chemical and structural investigation of γ-oryzanol loading inside a model lipid nanoparticle drug delivery system composed of cetyl palmitate as solid lipid and Miglyol 812® as liquid lipid. The lipid nanoparticles were prepared by high pressure homogenization at varying liquid lipid content, in comparison with the γ-oryzanol free systems. The size of the lipid nanoparticles, as measured by the photon correlation spectroscopy, was found to decrease with increased liquid lipid content from 200 to 160 nm. High-resolution proton nuclear magnetic resonance (1H-NMR) measurements of the medium chain triglyceride of the liquid lipid has confirmed successful incorporation of the liquid lipid in the lipid nanoparticles. Differential scanning calorimetric and powder x-ray diffraction measurements provide complementary results to the 1H-NMR, whereby the crystallinity of the lipid nanoparticles diminishes with an increase in the liquid lipid content. For the distribution of γ-oryzanol inside the lipid nanoparticles, the 1H-NMR revealed that the chemical shifts of the liquid lipid in γ-oryzanol loaded systems were found at rather higher field than those in γ-oryzanol free systems, suggesting incorporation of γ-oryzanol in the liquid lipid. In addition, the phase-separated structure was observed by atomic force microscopy for lipid nanoparticles with 0% liquid lipid, but not for lipid nanoparticles with 5 and 10% liquid lipid. Raman spectroscopic and mapping measurements further revealed preferential incorporation of γ-oryzanol in the liquid part rather than the solid part of in the lipid nanoparticles. Simple models representing the distribution of γ-oryzanol and

  8. Chemical and structural investigation of lipid nanoparticles: drug-lipid interaction and molecular distribution

    International Nuclear Information System (INIS)

    Anantachaisilp, Suranan; Smith, Siwaporn Meejoo; Treetong, Alongkot; Ruktanonchai, Uracha Rungsardthong; Pratontep, Sirapat; Puttipipatkhachorn, Satit

    2010-01-01

    Lipid nanoparticles are a promising alternative to existing carriers in chemical or drug delivery systems. A key challenge is to determine how chemicals are incorporated and distributed inside nanoparticles, which assists in controlling chemical retention and release characteristics. This study reports the chemical and structural investigation of γ-oryzanol loading inside a model lipid nanoparticle drug delivery system composed of cetyl palmitate as solid lipid and Miglyol 812 as liquid lipid. The lipid nanoparticles were prepared by high pressure homogenization at varying liquid lipid content, in comparison with the γ-oryzanol free systems. The size of the lipid nanoparticles, as measured by the photon correlation spectroscopy, was found to decrease with increased liquid lipid content from 200 to 160 nm. High-resolution proton nuclear magnetic resonance ( 1 H-NMR) measurements of the medium chain triglyceride of the liquid lipid has confirmed successful incorporation of the liquid lipid in the lipid nanoparticles. Differential scanning calorimetric and powder x-ray diffraction measurements provide complementary results to the 1 H-NMR, whereby the crystallinity of the lipid nanoparticles diminishes with an increase in the liquid lipid content. For the distribution of γ-oryzanol inside the lipid nanoparticles, the 1 H-NMR revealed that the chemical shifts of the liquid lipid in γ-oryzanol loaded systems were found at rather higher field than those in γ-oryzanol free systems, suggesting incorporation of γ-oryzanol in the liquid lipid. In addition, the phase-separated structure was observed by atomic force microscopy for lipid nanoparticles with 0% liquid lipid, but not for lipid nanoparticles with 5 and 10% liquid lipid. Raman spectroscopic and mapping measurements further revealed preferential incorporation of γ-oryzanol in the liquid part rather than the solid part of in the lipid nanoparticles. Simple models representing the distribution of γ-oryzanol and

  9. Lipid alterations in lipid rafts from Alzheimer's disease human brain cortex.

    Science.gov (United States)

    Martín, Virginia; Fabelo, Noemí; Santpere, Gabriel; Puig, Berta; Marín, Raquel; Ferrer, Isidre; Díaz, Mario

    2010-01-01

    Lipid rafts are membrane microdomains intimately associated with cell signaling. These biochemical microstructures are characterized by their high contents of sphingolipids, cholesterol and saturated fatty acids and a reduced content of polyunsaturated fatty acids (PUFA). Here, we have purified lipid rafts of human frontal brain cortex from normal and Alzheimer's disease (AD) and characterized their biochemical lipid composition. The results revealed that lipid rafts from AD brains exhibit aberrant lipid profiles compared to healthy brains. In particular, lipid rafts from AD brains displayed abnormally low levels of n-3 long chain polyunsaturated fatty acids (LCPUFA, mainly 22:6n-3, docosahexaenoic acid) and monoenes (mainly 18:1n-9, oleic acid), as well as reduced unsaturation and peroxidability indexes. Also, multiple relationships between phospholipids and fatty acids were altered in AD lipid rafts. Importantly, no changes were observed in the mole percentage of lipid classes and fatty acids in rafts from normal brains throughout the lifespan (24-85 years). These indications point to the existence of homeostatic mechanisms preserving lipid raft status in normal frontal cortex. The disruption of such mechanisms in AD brains leads to a considerable increase in lipid raft order and viscosity, which may explain the alterations in lipid raft signaling observed in AD.

  10. One-Pot Synthesis of (+)-Nootkatone via Dark Singlet Oxygenation of Valencene: The Triple Role of the Amphiphilic Molybdate Catalyst

    OpenAIRE

    Bing Hong; Raphaël Lebeuf; Stéphanie Delbaere; Paul L. Alsters; Véronique Nardello-Rataj

    2016-01-01

    Efficient one-pot catalytic synthesis of (+)-nootkatone was performed from (+)-valencene using only hydrogen peroxide and amphiphilic molybdate ions. The process required no solvent and proceeded in three cascade reactions: (i) singlet oxygenation of valencene according to the ene reaction; (ii) Schenck rearrangement of one hydroperoxide into the secondary β-hydroperoxide; and (iii) dehydration of the hydroperoxide into the desired (+)-nootkatone. The solvent effect on the hydroperoxide rearr...

  11. Measurement of surface contamination by certain antineoplastic drugs using high-performance liquid chromatography: applications in occupational hygiene investigations in hospital environments.

    Science.gov (United States)

    Rubino, F M; Floridia, L; Pietropaolo, A M; Tavazzani, M; Colombi, A

    1999-01-01

    Within the context of continuing interest in occupational hygiene of hospitals as workplaces, the authors report the results of a preliminary study on surface contamination by certain antineoplastic drugs (ANDs), recently performed in eight cancer departments of two large general hospitals in Milan, Italy. Since reliable quantitative information on the exposure levels to individual drugs is mandatory to establish a strong interpretative framework for correctly assessing the health risks associated with manipulation of ANDs and rationally advise intervention priorities for exposure abatement, two automated analytical methods were set up using reverse-phase high-performance liquid chromatography for the measurement of contamination by 1) methotrexate (MTX) and 2) the three most important nucleoside analogue antineoplastic drugs (5-fluorouracil 5FU, Cytarabin CYA, Gemcytabin GCA) on surfaces such as those of preparation hoods and work-benches in the pharmacies of cancer wards. The methods are characterized by short analysis time (7 min) under isocratic conditions, by the use of a mobile phase with a minimal content of organic solvent and by high sensitivity, adequate to detect surface contamination in the 5-10 micrograms/m2 range. To exemplify the performance of the analytical methods in the assessment of contamination levels from the target analyte ANDs, data are reported on the contamination levels measured on various surfaces (such as on handles, floor surfaces and window panes, even far from the preparation hood). Analyte concentrations corresponding to 0.8-1.5 micrograms of 5FU were measured on telephones, 0.85-28 micrograms/m2 of CYA were measured on tables, 1.2-1150 micrograms/m2 of GCA on furniture and floors. Spillage fractions between 1-5% of the used ANDs (daily use 5FU 7-13 g; CYA 0.1-7.1 g; GCA 0.2-5 g) were measured on the disposable polythene-backed paper cover sheet of the preparation hood.

  12. Amphiphilic star block copolymers as gene carrier Part I: Synthesis via ATRP using calix[4]resorcinarene-based initiators and characterization

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Anna; Xue, Yan; Wei, Dafu [Shanghai Key Laboratory of Advanced Polymeric Materials, Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237 (China); Guan, Yong, E-mail: yguan@ecust.edu.cn [Shanghai Key Laboratory of Advanced Polymeric Materials, Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237 (China); Xiao, Huining [Department of Chemical Engineering, University of New Brunswick, Fredericton, New Brunswick, Canada E3B 5A3 (Canada)

    2013-01-01

    In this work, a cationic star polymer [poly(2-dimethylamino)ethyl methacrylate (PDMAEMA)] was prepared via atom transfer radical polymerization (ATRP), using brominated calix[4]resorcinarene as an initiator. Hydrophobic moieties, methyl methacrylate (MMA) and butyl acrylate (BA), were further incorporated via 'one-pot' method. Well-defined eight-armed star block copolymers bearing hydrophilic blocks inside and hydrophobic blocks outside were synthesized. The molecular weight, particle size, electrophoretic mobility and apparent charge density were determined by gel permeation chromatography (GPC), dynamic light scattering (DLS), phase analysis light scattering (PALS) and colloidal titration, respectively. The zeta potentials and apparent charge densities of the products exhibited the characteristics of polyelectrolyte. The incorporation of hydrophobic moieties generated electrostatic screening effect. The as-synthesized amphiphilic star copolymer is promising as a thermo-sensitive gene carrier for gene therapy. Highlights: Black-Right-Pointing-Pointer Amphiphilic cationic star block copolymers with well-controlled structures were prepared via ATRP. Black-Right-Pointing-Pointer The molecular structures and properties of the initiator and copolymers were systematically characterized. Black-Right-Pointing-Pointer The products exhibited the positive charged character, and hydrophobic moieties generated electrostatic screening effect.

  13. Codelivery for Paclitaxel and Bcl-2 Conversion Gene by PHB-PDMAEMA Amphiphilic Cationic Copolymer for Effective Drug Resistant Cancer Therapy.

    Science.gov (United States)

    Wang, Xiaoyuan; Liow, Sing Shy; Wu, Qiaoqiong; Li, Chuang; Owh, Cally; Li, Zibiao; Loh, Xian Jun; Wu, Yun-Long

    2017-11-01

    Antiapoptotic Bcl-2 protein's upregulated expression is a key reason for drug resistance leading to failure of chemotherapy. In this report, a series of biocompatible amphiphilic cationic poly[(R)-3-hydroxybutyrate] (PHB)-b-poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) copolymer, comprising hydrophobic PHB block and cationic PDMAEMA block, is designed to codeliver hydrophobic chemotherapeutic paclitaxel and Bcl-2 converting gene Nur77/ΔDBD with enhanced stability, due to the micelle formation by hydrophobic PHB segment. This copolymer shows less toxicity but similar gene transfection efficiency to polyethyenimine (25k). More importantly, this codelivery approach by PHB-PDMAEMA leads to increased drug resistant HepG2/Bcl-2 cancer cell death, by increased expression of Nur77 proteins in the Bcl-2 present intracellular mitochondria. This work signifies for the first time that cationic amphiphilic PHB-b-PDMAEMA copolymers can be utilized for the drug and gene codelivery to drug resistant cancer cells with high expression of antiapoptosis Bcl-2 protein and the positive results are encouraging for the further design of codelivery platforms for combating drug resistant cancer cells. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Cationic Amphiphilic Tris-Cyclometalated Iridium(III) Complexes Induce Cancer Cell Death via Interaction with Ca2+-Calmodulin Complex.

    Science.gov (United States)

    Hisamatsu, Yosuke; Suzuki, Nozomi; Masum, Abdullah-Al; Shibuya, Ai; Abe, Ryo; Sato, Akira; Tanuma, Sei-Ichi; Aoki, Shin

    2017-02-15

    In our previous paper, we reported on the preparation of some cationic amphiphilic Ir complexes (2c, 2d) containing KKGG peptides that induce and detect cell death of Jurkat cells. Mechanistic studies suggest that 2c interacts with anionic molecules and/or membrane receptors on the cell surface to trigger an intracellular Ca 2+ response, resulting in the induction of cell death, accompanied by membrane disruption. We have continued the studies of cell death of Jurkat cells induced by 2c and found that xestospongin C, a selective inhibitor of an inositol 1,4,5-trisphosphate receptor located on the endoplasmic reticulum (ER), reduces the cytotoxicity of 2c, suggesting that 2c triggers the release of Ca 2+ from the ER, leading to an increase in the concentration of cytosolic Ca 2+ , thus inducing cell death. Moreover, we synthesized a series of new amphiphilic cationic Ir complexes 5a-c containing photoreactive 3-trifluoromethyl-3-phenyldiazirine (TFPD) groups, in an attempt to identify the target molecules of 2c. Interestingly, it was discovered that a TFPD group functions as a triplet quencher of Ir complexes. It was also found that 5b is useful as a turn-on phosphorescent probe of acidic proteins such as bovine serum albumin (BSA) (pI = 4.7) and their complexation was confirmed by luminescence titrations and SDS-PAGE of photochemical products between them. These successful results allowed us to carry out photoaffinity labeling of the target biomolecules of 5b (2c and analogues thereof) in Jurkat cells. A proteomic analysis of the products obtained by the photoirradiation of 5b with Jurkat cells suggests that the Ca 2+ -binding protein "calmodulin (CaM)" is one of target proteins of the Ir complexes. Indeed, 5b was found to interact with the Ca 2+ -CaM complex, as evidenced by luminescence titrations and the results of photochemical reactions of 5b with CaM in the presence of Ca 2+ (SDS-PAGE). A plausible mechanism for cell death induced by a cationic amphiphilic Ir

  15. Chemical and structural investigation of lipid nanoparticles: drug-lipid interaction and molecular distribution

    Energy Technology Data Exchange (ETDEWEB)

    Anantachaisilp, Suranan; Smith, Siwaporn Meejoo [Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Mahidol University, Rama VI Road, Bangkok 10400 (Thailand); Treetong, Alongkot; Ruktanonchai, Uracha Rungsardthong [National Nanotechnology Center, National Science and Technology Development Agency, 111 Thailand Science Park, Paholyothin Road, Klong 1, Klong Luang, Pathumthani 12120 (Thailand); Pratontep, Sirapat [College of KMITL Nanotechnology, King Mongkut' s Institute of Technology Ladkrabang, Bangkok (Thailand); Puttipipatkhachorn, Satit, E-mail: uracha@nanotec.or.th [Department of Manufacturing Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok 10400 (Thailand)

    2010-03-26

    Lipid nanoparticles are a promising alternative to existing carriers in chemical or drug delivery systems. A key challenge is to determine how chemicals are incorporated and distributed inside nanoparticles, which assists in controlling chemical retention and release characteristics. This study reports the chemical and structural investigation of {gamma}-oryzanol loading inside a model lipid nanoparticle drug delivery system composed of cetyl palmitate as solid lipid and Miglyol 812 as liquid lipid. The lipid nanoparticles were prepared by high pressure homogenization at varying liquid lipid content, in comparison with the {gamma}-oryzanol free systems. The size of the lipid nanoparticles, as measured by the photon correlation spectroscopy, was found to decrease with increased liquid lipid content from 200 to 160 nm. High-resolution proton nuclear magnetic resonance ({sup 1}H-NMR) measurements of the medium chain triglyceride of the liquid lipid has confirmed successful incorporation of the liquid lipid in the lipid nanoparticles. Differential scanning calorimetric and powder x-ray diffraction measurements provide complementary results to the {sup 1}H-NMR, whereby the crystallinity of the lipid nanoparticles diminishes with an increase in the liquid lipid content. For the distribution of {gamma}-oryzanol inside the lipid nanoparticles, the {sup 1}H-NMR revealed that the chemical shifts of the liquid lipid in {gamma}-oryzanol loaded systems were found at rather higher field than those in {gamma}-oryzanol free systems, suggesting incorporation of {gamma}-oryzanol in the liquid lipid. In addition, the phase-separated structure was observed by atomic force microscopy for lipid nanoparticles with 0% liquid lipid, but not for lipid nanoparticles with 5 and 10% liquid lipid. Raman spectroscopic and mapping measurements further revealed preferential incorporation of {gamma}-oryzanol in the liquid part rather than the solid part of in the lipid nanoparticles. Simple models

  16. Incorporation of nano-clay saponite layers in the organo-clay hybrid films using anionic amphiphile stearic acid by Langmuir–Blodgett technique

    Energy Technology Data Exchange (ETDEWEB)

    Hussain, Syed Arshad, E-mail: sa_h153@hotmail.com [Department of Physics, Tripura University, Suryamaninagar-799022 (India); Chakraborty, S.; Bhattacharjee, D. [Department of Physics, Tripura University, Suryamaninagar-799022 (India); Schoonheydt, R.A. [Centres for Surface Chemistry and Catalysis, K.U. Leuven, Kasteelpark Arenberg 23, 3001 Leuven (Belgium)

    2013-06-01

    In general cationic amphiphiles are used to prepare organo-clay hybrid film in Langmuir–Blodgett (LB) technique. In this present communication we demonstrated a unique technique to prepare the organo–clay hybrid films using an anionic amphiphile. The T–O–T type clay saponite was incorporated onto a floating stearic acid monolayer via a divalent cation Mg{sup 2+}. Salt MgCl{sub 2} was mixed along with the clay dispersion in the LB trough and amphiphile solution was spread onto the subphase in order to make the organo-clay hybrid films. It was observed that salt (MgCl{sub 2}) concentration on the subphase affects the organization of nano-dimensional clay platelet (saponite) in organo-clay hybrid films at air–water interface as well as in LB films. Noticeable changes in area per molecule and shape of the isotherms were observed and measured at subphases with different salt concentrations. Infrared reflection absorption spectroscopy studies reveal that only an in-plane (996 cm{sup −1}) vibration of ν (Si-O) band occurred when the salt concentration was 10 mM. However, both in-plane (996 cm{sup −1}) and out-of-plane (1063 cm{sup −1}) vibrations of the ν (Si-O) band of saponite occurred when the subphase salt concentration was 100 mM. Also the out-of-plane vibration of ν (OH) of saponite was prominent at higher salt concentration. This is because at lower salt concentration clay sheets remain flat on the surface whereas; at higher MgCl{sub 2} concentration they aggregated and form stacks of saponite layers. Also they may be slightly tilted with a very small tilt angle at higher salt concentration making a favorable condition for both in-plane and out-of-plane vibrations of ν (Si-O) in the hybrid films. Observed decrease in starting area per molecule in the pressure area isotherm measured at higher salt concentration also supports the tilting of clay layers at air–clay dispersion interface. Attentuated total reflectance Fourier transform infrared

  17. Membrane curvature, lipid segregation, and structural transitions for phospholipids under dual-solvent stress

    International Nuclear Information System (INIS)

    Rand, R.P.; Fuller, N.L.; Gruner, S.M.; Parsegian, V.A.

    1990-01-01

    Amphiphiles respond both to polar and to nonpolar solvents. In this paper X-ray diffraction and osmotic stress have been used to examine the phase behavior, the structural dimensions, and the work of deforming the monolayer-lined aqueous cavities formed by mixtures of dioleoylphosphatidylethanolamine (DOPE) and dioleoylphosphatidylcholine (DOPC) as a function of the concentration of two solvents, water and tetradecane (td). In the absence of td, most PE/PC mixtures show only lamellar phases in excess water; all of these become single reverse hexagonal (H II ) phases with addition of excess td. The spontaneous radius of curvature R 0 of lipid monolayers, as expressed in these H II phases, is allowed by the relief of hydrocarbon chain stress by td; R 0 increases with the ratio DOPC/DOPE. Single H II phases stressed by limited water or td show several responses. (a) the molecular area is compressed at the polar end of the molecule and expanded at the hydrocarbon ends. (b) For circularly symmetrical water cylinders, the degrees of hydrocarbon chain splaying and polar group compression are different for molecules aligned in different directions around the water cylinder. (c) A pivotal position exists along the length of the phospholipid molecule where little area change occurs as the monolayer is bent to increasing curvatures. (d) By defining R 0 at the pivotal position, the authors find that measured energies are well fit by a quadratic bending energy. (e) For lipid mixtures, enforced deviation of the H II monolayer from R 0 is sufficiently powerful to cause demixing of the phospholipids in a way suggesting that the DOPE/DOPC ratio self-adjusts so that its R 0 matches the amount of td or water available, i.e., that curvature energy is minimized

  18. Screening nylon-3 polymers, a new class of cationic amphiphiles, for siRNA delivery.

    Science.gov (United States)

    Nadithe, Venkatareddy; Liu, Runhui; Killinger, Bryan A; Movassaghian, Sara; Kim, Na Hyung; Moszczynska, Anna B; Masters, Kristyn S; Gellman, Samuel H; Merkel, Olivia M

    2015-02-02

    Amphiphilic nucleic acid carriers have attracted strong interest. Three groups of nylon-3 copolymers (poly-β-peptides) possessing different cationic/hydrophobic content were evaluated as siRNA delivery agents in this study. Their ability to condense siRNA was determined in SYBR Gold assays. Their cytotoxicity was tested by MTT assays, their efficiency of delivering Alexa Fluor-488-labeled siRNA intracellularly in the presence and absence of uptake inhibitors was assessed by flow cytometry, and their transfection efficacies were studied by luciferase knockdown in a cell line stably expressing luciferase (H1299/Luc). Endosomal release was determined by confocal laser scanning microscopy and colocalization with lysotracker. All polymers efficiently condensed siRNA at nitrogen-to-phosphate (N/P) ratios of 5 or lower, as reflected in hydrodynamic diameters smaller than that at N/P 1. Although several formulations had negative zeta potentials at N/P 1, G2C and G2D polyplexes yielded >80% uptake in H1299/Luc cells, as determined by flow cytometry. Luciferase knockdown (20-65%) was observed after transfection with polyplexes made of the high molecular weight polymers that were the most hydrophobic. The ability of nylon-3 polymers to deliver siRNA intracellularly even at negative zeta potential implies that they mediate transport across cell membranes based on their amphiphilicity. The cellular uptake route was determined to strongly depend on the presence of cholesterol in the cell membrane. These polymers are, therefore, very promising for siRNA delivery at reduced surface charge and toxicity. Our study identified nylon-3 formulations at low N/P ratios for effective gene knockdown, indicating that nylon-3 polymers are a new, promising type of gene delivery agent.

  19. Screening Nylon-3 Polymers, a New Class of Cationic Amphiphiles, for siRNA Delivery

    Science.gov (United States)

    2015-01-01

    Amphiphilic nucleic acid carriers have attracted strong interest. Three groups of nylon-3 copolymers (poly-β-peptides) possessing different cationic/hydrophobic content were evaluated as siRNA delivery agents in this study. Their ability to condense siRNA was determined in SYBR Gold assays. Their cytotoxicity was tested by MTT assays, their efficiency of delivering Alexa Fluor-488-labeled siRNA intracellularly in the presence and absence of uptake inhibitors was assessed by flow cytometry, and their transfection efficacies were studied by luciferase knockdown in a cell line stably expressing luciferase (H1299/Luc). Endosomal release was determined by confocal laser scanning microscopy and colocalization with lysotracker. All polymers efficiently condensed siRNA at nitrogen-to-phosphate (N/P) ratios of 5 or lower, as reflected in hydrodynamic diameters smaller than that at N/P 1. Although several formulations had negative zeta potentials at N/P 1, G2C and G2D polyplexes yielded >80% uptake in H1299/Luc cells, as determined by flow cytometry. Luciferase knockdown (20–65%) was observed after transfection with polyplexes made of the high molecular weight polymers that were the most hydrophobic. The ability of nylon-3 polymers to deliver siRNA intracellularly even at negative zeta potential implies that they mediate transport across cell membranes based on their amphiphilicity. The cellular uptake route was determined to strongly depend on the presence of cholesterol in the cell membrane. These polymers are, therefore, very promising for siRNA delivery at reduced surface charge and toxicity. Our study identified nylon-3 formulations at low N/P ratios for effective gene knockdown, indicating that nylon-3 polymers are a new, promising type of gene delivery agent. PMID:25437915

  20. Facile synthesis and characterization of novel biodegradable amphiphilic block copolymers bearing pendant hydroxyl groups

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Gaicen; Fan, Xiaoshan; Xu, Bingcan; Zhang, Delong; Hu, Zhiguo, E-mail: zghu@htu.cn

    2014-10-01

    Novel amphiphilic block copolymers bearing pendant hydroxyl groups polylactide-b–poly(3,3-bis(Hydroxymethyl–triazolylmethyl) oxetane)-b–polylactide (PLA-b–PHMTYO-b–PLA) were synthesized via a facile and efficient method. First, the block copolymer intermediates polylactide-b–poly(3,3-Diazidomethyloxetane)-b–polylactide (PLA-b–PBAMO-b–PLA) were synthesized through ring-opening polymerization of lactide using PBAMO as a macroinitiator. Following “Click” reaction of PLA-b–PBAMO-b–PLA with propargyl alcohol provided the targeted amphiphilic block copolymers PLA-b–PHMTYO-b–PLA with pendant hydroxyl groups. The composition and structure of prepared copolymers were characterized by {sup 1}H nuclear magnetic resonance ({sup 1}H NMR) spectroscopy, Fourier transform infrared (FT-IR) and gel permeation chromatography (GPC). The self-assembly behavior of the copolymers in water was investigated by transmission electron microscope (TEM), dynamic light scattering (DLS) and static light scattering (SLS). The results showed that the novel copolymers PLA-b–PHMTYO-b–PLA self-assembled into spherical micelles with diameters ranging from 100 nm to 200 nm in aqueous solution. These copolymers also exhibited low critical micellar concentrations (CMC: 6.9 × 10{sup −4} mg/mL and 3.9 × 10{sup −5} mg/mL, respectively). In addition, the in vitro cytotoxicity of these copolymers was determined in the presence of L929 cells. The results showed that the block copolymers PLA-b–PHMTYO-b–PLA exhibited better biocompatibility. Therefore, these well-defined copolymers are expected to find some applications in drug delivery or tissue engineering. - Highlights: • The method to synthesize PLA-b–PHMTYO-b–PLA is relatively facile and efficient. • PLA-b–PHMTYO-b–PLA self-assembles into spherical micelles with low CMC in water. • PLA-b–PHMTYO-b–PLA exhibits better biocompatibility and biodegradability.

  1. Facile synthesis and characterization of novel biodegradable amphiphilic block copolymers bearing pendant hydroxyl groups

    International Nuclear Information System (INIS)

    Hu, Gaicen; Fan, Xiaoshan; Xu, Bingcan; Zhang, Delong; Hu, Zhiguo

    2014-01-01

    Novel amphiphilic block copolymers bearing pendant hydroxyl groups polylactide-b–poly(3,3-bis(Hydroxymethyl–triazolylmethyl) oxetane)-b–polylactide (PLA-b–PHMTYO-b–PLA) were synthesized via a facile and efficient method. First, the block copolymer intermediates polylactide-b–poly(3,3-Diazidomethyloxetane)-b–polylactide (PLA-b–PBAMO-b–PLA) were synthesized through ring-opening polymerization of lactide using PBAMO as a macroinitiator. Following “Click” reaction of PLA-b–PBAMO-b–PLA with propargyl alcohol provided the targeted amphiphilic block copolymers PLA-b–PHMTYO-b–PLA with pendant hydroxyl groups. The composition and structure of prepared copolymers were characterized by 1 H nuclear magnetic resonance ( 1 H NMR) spectroscopy, Fourier transform infrared (FT-IR) and gel permeation chromatography (GPC). The self-assembly behavior of the copolymers in water was investigated by transmission electron microscope (TEM), dynamic light scattering (DLS) and static light scattering (SLS). The results showed that the novel copolymers PLA-b–PHMTYO-b–PLA self-assembled into spherical micelles with diameters ranging from 100 nm to 200 nm in aqueous solution. These copolymers also exhibited low critical micellar concentrations (CMC: 6.9 × 10 −4 mg/mL and 3.9 × 10 −5 mg/mL, respectively). In addition, the in vitro cytotoxicity of these copolymers was determined in the presence of L929 cells. The results showed that the block copolymers PLA-b–PHMTYO-b–PLA exhibited better biocompatibility. Therefore, these well-defined copolymers are expected to find some applications in drug delivery or tissue engineering. - Highlights: • The method to synthesize PLA-b–PHMTYO-b–PLA is relatively facile and efficient. • PLA-b–PHMTYO-b–PLA self-assembles into spherical micelles with low CMC in water. • PLA-b–PHMTYO-b–PLA exhibits better biocompatibility and biodegradability

  2. Effect of Amphiphiles on the Rheology of Triglyceride Networks

    Science.gov (United States)

    Seth, Jyoti

    2014-11-01

    Networks of aggregated crystallites form the structural backbone of many products from the food, cosmetic and pharmaceutical industries. Such materials are generally formulated by cooling a saturated solution to yield the desired solid fraction. Crystal nucleation and growth followed by aggregation leads to formation of a space percolating fractal-network. It is understood that microstructural hierarchy and particle-particle interactions determine material behavior during processing, storage and use. In this talk, rheology of suspensions of triglycerides (TAG, like tristearin) will be explored. TAGs exhibit a rich assortment of polymorphs and form suspensions that are evidently sensitive to surface modifying additives like surfactants and polymers. Here, a theoretical framework will be presented for suspensions containing TAG crystals interacting via pairwise potentials. The work builds on existing models of fractal aggregates to understand microstructure and its correlation with material rheology. Effect of amphiphilic additives is derived through variation of particle-particle interactions. Theoretical predictions for storage modulus will be compared against experimental observations and data from the literature and micro structural predictions against microscopy. Such a theory may serve as a step towards predicting short and long-term behavior of aggregated suspensions formulated via crystallization.

  3. Tuning peptide amphiphile supramolecular structure for biomedical applications

    Science.gov (United States)

    Pashuck, Eugene Thomas, III

    The use of biomaterials in regenerative medicine has been an active area of research for more than a decade. Peptide amphiphiles, which are short peptide sequences coupled to alkyl tails, have been studied in the Stupp group since the beginning of the decade and been used for a variety of biomedical applications. Most of the work has focused on the bioactive epitopes places on the periphery of the PA molecules, but the interior amino acids, known as the beta-sheet region, give the PA nanofiber gel much of its mechanical strength. To study the important parameters in the beta-sheet region, six PA molecules were constructed to determine the influence of beta-sheet length and order of the amino acids in the beta-sheet. It was found that having beta-sheet forming amino acids near the center of the fiber improves PA gel stiffness, and that having extra amino acids that have preferences for other secondary structures, like alpha-helix decreased the gels stiffness. Using FTIR and circular dichroism it was found that the mechanical properties are influenced by the amount of twist in the beta-sheet, and PAs that have more twisted beta-sheets form weaker gels. The effect amino acid properties have on peptide amphiphile self-assembly where studied by synthesizining molecules with varying side group size and hydrophobicity. It was found that smaller amino acids lead to stiffer gels and when two amino acids had the same size the amino acid with the larger beta-sheet propensity lead to a stiffer gel. Furthermore, small changes in peptide structure were found to lead to big changes in nanostructure, as leucine and isoleucine, which have the same size but slightly different structures, form flat ribbons and cylindrical nanofibers, respectively. Phenylalanine and alanine were studied more indepth because they represent the effects of adding an aromatic group to amino acids in the beta-sheet regon. These phenylalanine PAs formed short, twisted ribbons when freshly dissolved in water

  4. Amphiphilic core shell nanoparticles containing dense polyethyleneimine shells for efficient delivery of microRNA to Kupffer cells

    Directory of Open Access Journals (Sweden)

    Liu Z

    2016-06-01

    Full Text Available Zuojin Liu,1,* Dechao Niu,2,3,* Junyong Zhang,1 Wenfeng Zhang,1 Yuan Yao,2 Pei Li,2 Jianping Gong1 1Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 2Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, 3Lab of Low-Dimensional Materials Chemistry, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: Efficient and targeted delivery approach to transfer exogenous genes into macrophages is still a great challenge. Current gene delivery methods often result in low cellular uptake efficiency in vivo in some types of cells, especially for the Kupffer cells (KCs. In this article, we demonstrate that amphiphilic core–shell nanoparticles (NPs consisting of well-defined hydrophobic poly(methyl methacrylate (PMMA cores and branched polyethyleneimine (PEI shells (denoted as PEI@PMMA NPs are efficient nanocarriers to deliver microRNA (miRNA-loaded plasmid to the KCs. Average hydrodynamic diameter of PEI@PMMA NPs was 279 nm with a narrow size distribution. The NPs also possessed positive surface charges up to +30 mV in water, thus enabling effective condensation of negatively charged plasmid DNA. Gel electrophoresis assay showed that the resultant PEI@PMMA NPs were able to completely condense miRNA plasmid at a weight ratio of 25:1 (N/P ratio equal to 45:1. The Cell Counting Kit-8 assay and flow cytometry results showed that the PEI@PMMA/miRNA NPs displayed low cytotoxicity and cell apoptosis activity against the KCs. The maximum cell transfection efficiency reached 34.7% after 48 hours, which is much higher than that obtained by using the commercial Lipofectamine™ 2000 (1.7%. Bio-transmission electron microscope observation revealed that the PEI@PMMA NPs were mainly distributed in

  5. Lipid somersaults

    DEFF Research Database (Denmark)

    Günther-Pomorski, Thomas; Menon, Anant K.

    2016-01-01

    Membrane lipids diffuse rapidly in the plane of the membrane but their ability to flip spontaneously across a membrane bilayer is hampered by a significant energy barrier. Thus spontaneous flip-flop of polar lipids across membranes is very slow, even though it must occur rapidly to support diverse...... aspects of cellular life. Here we discuss the mechanisms by which rapid flip-flop occurs, and what role lipid flipping plays in membrane homeostasis and cell growth. We focus on conceptual aspects, highlighting mechanistic insights from biochemical and in silico experiments, and the recent, ground......-breaking identification of a number of lipid scramblases....

  6. Acentric 2-D ensembles of D-br-A electron-transfer chromophores via vectorial orientation within amphiphilic n-helix bundle peptides for photovoltaic device applications.

    Science.gov (United States)

    Koo, Jaseung; Park, Jaehong; Tronin, Andrey; Zhang, Ruili; Krishnan, Venkata; Strzalka, Joseph; Kuzmenko, Ivan; Fry, H Christopher; Therien, Michael J; Blasie, J Kent

    2012-02-14

    We show that simply designed amphiphilic 4-helix bundle peptides can be utilized to vectorially orient a linearly extended donor-bridge-acceptor (D-br-A) electron transfer (ET) chromophore within its core. The bundle's interior is shown to provide a unique solvation environment for the D-br-A assembly not accessible in conventional solvents and thereby control the magnitudes of both light-induced ET and thermal charge recombination rate constants. The amphiphilicity of the bundle's exterior was employed to vectorially orient the peptide-chromophore complex at a liquid-gas interface, and its ends were tailored for subsequent covalent attachment to an inorganic surface, via a "directed assembly" approach. Structural data, combined with evaluation of the excited state dynamics exhibited by these peptide-chromophore complexes, demonstrate that densely packed, acentrically ordered 2-D monolayer ensembles of such complexes at high in-plane chromophore densities approaching 1/200 Å(2) offer unique potential as active layers in binary heterojunction photovoltaic devices.

  7. Muscle Lipid Metabolism: Role of Lipid Droplets and Perilipins

    Directory of Open Access Journals (Sweden)

    Pablo Esteban Morales

    2017-01-01

    Full Text Available Skeletal muscle is one of the main regulators of carbohydrate and lipid metabolism in our organism, and therefore, it is highly susceptible to changes in glucose and fatty acid (FA availability. Skeletal muscle is an extremely complex tissue: its metabolic capacity depends on the type of fibers it is made up of and the level of stimulation it undergoes, such as acute or chronic contraction. Obesity is often associated with increased FA levels, which leads to the accumulation of toxic lipid intermediates, oxidative stress, and autophagy in skeletal fibers. This lipotoxicity is one of the most common causes of insulin resistance (IR. In this scenario, the “isolation” of certain lipids in specific cell compartments, through the action of the specific lipid droplet, perilipin (PLIN family of proteins, is conceived as a lifeguard compensatory strategy. In this review, we summarize the cellular mechanism underlying lipid mobilization and metabolism inside skeletal muscle, focusing on the function of lipid droplets, the PLIN family of proteins, and how these entities are modified in exercise, obesity, and IR conditions.

  8. Lxr-driven enterocyte lipid droplet formation delays transport of ingested lipids.

    Science.gov (United States)

    Cruz-Garcia, Lourdes; Schlegel, Amnon

    2014-09-01

    Liver X receptors (Lxrs) are master regulators of cholesterol catabolism, driving the elimination of cholesterol from the periphery to the lumen of the intestine. Development of pharmacological agents to activate Lxrs has been hindered by synthetic Lxr agonists' induction of hepatic lipogenesis and hypertriglyceridemia. Elucidating the function of Lxrs in regulating enterocyte lipid handling might identify novel aspects of lipid metabolism that are pharmacologically amenable. We took a genetic approach centered on the single Lxr gene nr1h3 in zebrafish to study the role of Lxr in enterocyte lipid metabolism. Loss of nr1h3 function causes anticipated gene regulatory changes and cholesterol intolerance, collectively reflecting high evolutionary conservation of zebrafish Lxra function. Intestinal nr1h3 activation delays transport of absorbed neutral lipids, with accumulation of neutral lipids in enterocyte cytoplasmic droplets. This delay in transport of ingested neutral lipids protects animals from hypercholesterolemia and hepatic steatosis induced by a high-fat diet. On a gene regulatory level, Lxra induces expression of acsl3a, which encodes acyl-CoA synthetase long-chain family member 3a, a lipid droplet-anchored protein that directs fatty acyl chains into lipids. Forced overexpression of acls3a in enterocytes delays, in part, the appearance of neutral lipids in the vasculature of zebrafish larvae. Activation of Lxr in the intestine cell-autonomously regulates the rate of delivery of absorbed lipids by inducting a temporary lipid intestinal droplet storage depot. Copyright © 2014 by the American Society for Biochemistry and Molecular Biology, Inc.

  9. Nanotoxicity comparison of four amphiphilic polymeric micelles with similar hydrophilic or hydrophobic structure.

    Science.gov (United States)

    Zhao, Bo; Wang, Xue-Qing; Wang, Xiao-You; Zhang, Hua; Dai, Wen-Bing; Wang, Jun; Zhong, Zhen-Lin; Wu, Hou-Nan; Zhang, Qiang

    2013-10-03

    Nanocarriers represent an attractive means of drug delivery, but their biosafety must be established before their use in clinical research. Four kinds of amphiphilic polymeric (PEG-PG-PCL, PEEP-PCL, PEG-PCL and PEG-DSPE) micelles with similar hydrophilic or hydrophobic structure were prepared and their in vitro and in vivo safety were evaluated and compared. In vitro nanotoxicity evaluations included assessments of cell morphology, cell volume, inflammatory effects, cytotoxicity, apoptosis and membrane fluidity. An umbilical vein cell line (Eahy.926) and a kind of macrophages (J774.A1) were used as cell models considering that intravenous route is dominant for micelle delivery systems. In vivo analyses included complete blood count, lymphocyte subset analysis, detection of plasma inflammatory factors and histological observations of major organs after intravenous administration to KM mice. All the micelles enhanced inflammatory molecules in J774.A1 cells, likely resulting from the increased ROS levels. PEG-PG-PCL and PEEP-PCL micelles were found to increase the J774.A1 cell volume. This likely correlated with the size of PEG-PG-PCL micelles and the polyphosphoester structure in PEEP-PCL. PEG-DSPE micelles inhibited the growth of Eahy.926 cells via inducing apoptosis. This might relate to the structure of DSPE, which is a type of phospholipid and has good affinity with cell membrane. No evidence was found for cell membrane changes after treatment with these micelles for 24 h. In the in vivo study, during 8 days of 4 time injection, each of the four nanocarriers altered the hematic phase differently without changes in inflammatory factors or pathological changes in target organs. These results demonstrate that the micelles investigated exhibit diverse nanotoxicity correlated with their structures, their biosafety is different in different cell model, and there is no in vitro and in vivo correlation found. We believe that this study will certainly provide more

  10. pH-Sensitive Amphiphilic Block-Copolymers for Transport and Controlled Release of Oxygen

    KAUST Repository

    Patil, Yogesh Raghunath

    2017-05-31

    Saturated fluorocarbons, their derivatives and emulsions are capable of dissolving anomalously high amounts of oxygen and other gases. The mechanistic aspects of this remarkable effect remain to be explored experimentally. Here, the synthesis of a library of amphiphilic fluorous block-copolymers incorporating different fluorinated monomers is described, and the capacity of these copolymers for oxygen transport in water is systematically investigated. The structure of the fluorous monomer employed was found to have a profound effect on both the oxygen-carrying capacity and the gas release kinetics of the polymer emulsions. Furthermore, the release of O2 from the polymer dispersions could be triggered by changing the pH of the solution. This is the first example of a polymer-based system for controlled release of a non-polar, non-covalently entrapped respiratory gas.

  11. pH-Sensitive Amphiphilic Block-Copolymers for Transport and Controlled Release of Oxygen

    KAUST Repository

    Patil, Yogesh Raghunath; Almahdali, Sarah; Vu, Khanh B.; Zapsas, Georgios; Hadjichristidis, Nikolaos; Rodionov, Valentin

    2017-01-01

    Saturated fluorocarbons, their derivatives and emulsions are capable of dissolving anomalously high amounts of oxygen and other gases. The mechanistic aspects of this remarkable effect remain to be explored experimentally. Here, the synthesis of a library of amphiphilic fluorous block-copolymers incorporating different fluorinated monomers is described, and the capacity of these copolymers for oxygen transport in water is systematically investigated. The structure of the fluorous monomer employed was found to have a profound effect on both the oxygen-carrying capacity and the gas release kinetics of the polymer emulsions. Furthermore, the release of O2 from the polymer dispersions could be triggered by changing the pH of the solution. This is the first example of a polymer-based system for controlled release of a non-polar, non-covalently entrapped respiratory gas.

  12. Structure-property relationship in cytotoxicity and cell uptake of poly(2-oxazoline) amphiphiles

    KAUST Repository

    Luxenhofer, Robert

    2011-07-01

    The family of poly(2-oxazoline)s (POx) is being increasingly investigated in the context of biomedical applications. We tested the relative cytotoxicity of POx and were able to confirm that these polymers are typically not cytotoxic even at high concentrations. Furthermore, we report structure-uptake relationships of a series of amphiphilic POx block copolymers that have different architectures, molar mass and chain termini. The rate of endocytosis can be fine-tuned over a broad range by changing the polymer structure. The cellular uptake increases with the hydrophobic character of the polymers and is observed even at nanomolar concentrations. Considering the structural versatility of this class of polymers, the relative ease of preparation and their stability underlines the potential of POx as a promising platform candidate for the preparation of next-generation polymer therapeutics.

  13. Amplification of Chirality through Self-Replication of Micellar Aggregates in Water

    KAUST Repository

    Bukhriakov, Konstantin

    2015-03-17

    We describe a system in which the self-replication of micellar aggregates results in a spontaneous amplification of chirality in the reaction products. In this system, amphiphiles are synthesized from two "clickable" fragments: a water-soluble "head" and a hydrophobic "tail". Under biphasic conditions, the reaction is autocatalytic, as aggregates facilitate the transfer of hydrophobic molecules to the aqueous phase. When chiral, partially enantioenriched surfactant heads are used, a strong nonlinear induction of chirality in the reaction products is observed. Preseeding the reaction mixture with an amphiphile of one chirality results in the amplification of this product and therefore information transfer between generations of self-replicating aggregates. Because our amphiphiles are capable of catalysis, information transfer, and self-assembly into bounded structures, they present a plausible model for prenucleic acid "lipid world" entities. © 2015 American Chemical Society.

  14. Proteins mediating intra- and intercellular transport of lipids and lipid-modified proteins

    NARCIS (Netherlands)

    Neumann, S.

    2008-01-01

    Proteins mediating intra- and intercellular transport of lipids and lipid-modified proteins In this thesis, I studied the intra- and intercellular transport of lipidic molecules, in particular glycosphingolipids and lipid-modified proteins. The first part focuses on the intracellular transport of

  15. An approach to the construction of tailor-made amphiphilic peptides that strongly and selectively bind to hairpin RNA targets.

    Science.gov (United States)

    Lee, Su Jin; Hyun, Soonsil; Kieft, Jeffrey S; Yu, Jaehoon

    2009-02-18

    The hairpin RNA motif is one of the most frequently observed secondary structures and is often targeted by therapeutic agents. An amphiphilic peptide with seven lysine and eight leucine residues and its derivatives were designed for use as ligands against RNA hairpin motifs. We hypothesized that variations in both the hydrophobic leucine-rich and hydrophilic lysine-rich spheres of these amphiphilic peptides would create extra attractive interactions with hairpin RNA targets. A series of alanine-scanned peptides were probed to identify the most influential lysine residues in the hydrophilic sphere. The binding affinities of these modified peptides with several hairpins, such as RRE, TAR from HIV, a short hairpin from IRES of HCV, and a hairpin from the 16S A-site stem from rRNA, were determined. Since the hairpin from IRES of HCV was the most susceptible to the initial series of alanine-scanned peptides, studies investigating how further variations in the peptides effect binding employed the IRES hairpin. Next, the important Lys residues were substituted by shorter chain amines, such as ornithine, to place the peptide deeper into the hairpin groove. In a few cases, a 70-fold improved binding was observed for peptides that contained the specifically located shorter amine side chains. To further explore changes in binding affinities brought about by alterations in the hydrophobic sphere, tryptophan residues were introduced in place of leucine. A few peptides with tryptophan in specific positions also displayed 70-fold improved binding affinities. Finally, double mutant peptides incorporating both specifically located shorter amine side chains in the hydrophilic region and tryptophan residues in the hydrophobic region were synthesized. The binding affinities of peptides containing the simple double modification were observed to be 80 times lower, and their binding specificities were increased 40-fold. The results of this effort provide important information about

  16. Cell-based lipid flippase assay employing fluorescent lipid derivatives

    DEFF Research Database (Denmark)

    Jensen, Maria Stumph; Costa, Sara; Günther-Pomorski, Thomas

    2016-01-01

    P-type ATPases in the P4 subfamily (P4-ATPases) are transmembrane proteins unique for eukaryotes that act as lipid flippases, i.e., to translocate phospholipids from the exofacial to the cytofacial monolayer of cellular membranes. While initially characterized as aminophospholipid translocases, s...... flippase activities in the plasma membrane of cells, using yeast as an example.......P-type ATPases in the P4 subfamily (P4-ATPases) are transmembrane proteins unique for eukaryotes that act as lipid flippases, i.e., to translocate phospholipids from the exofacial to the cytofacial monolayer of cellular membranes. While initially characterized as aminophospholipid translocases......, studies of individual P4-ATPase family members from fungi, plants, and animals show that P4-ATPases differ in their substrate specificities and mediate transport of a broader range of lipid substrates. Here, we describe an assay based on fluorescent lipid derivatives to monitor and characterize lipid...

  17. Biological activity of some novel synthesized 2-(4-methylbenzenesulphonamidopentanedioic acid bis amide derivatives: In vitro and in vivo antineoplastic activity

    Directory of Open Access Journals (Sweden)

    Satyajit Dutta

    2014-12-01

    Full Text Available In the present work few novel 2-(4-methylbenzenesulphonamidopentanedioic acid bis amide derivatives and the basic compound 2-(4-methylphenylsulfonamidopentanedioic acid have been synthesized, characterized and screened for their possible antineoplastic activity both in vitro and in vivo. The in vitro activity was performed against five human cell lines like human breast cancer (MCF-7, leukemia (K-562, ovarian cancer (OVACAR-3, human colon adenocarcinoma (HT-29 and Human kidney carcinoma (A-498. The in vivo activity was performed in female swiss albino mice against Ehrlich ascites carcinoma (EAC. Among the synthesized compounds, ureide, anilide, p-nitoanilide and o-bromoanilide derivatives of 2-(4-methyl benzene sulphonyl-pentanedioic acid bis amides showed encouraging activity in both the in vitro and in vivo compared to other compounds.

  18. Synthesis of Fluorinated Amphiphilic Block Copolymers Based on PEGMA, HEMA, and MMA via ATRP and CuAAC Click Chemistry

    OpenAIRE

    Erol, Fatime Eren; Sinirlioglu, Deniz; Cosgun, Sedat; Muftuoglu, Ali Ekrem

    2014-01-01

    Synthesis of fluorinated amphiphilic block copolymers via atom transfer radical polymerization (ATRP) and Cu(I) catalyzed Huisgen 1,3-dipolar cycloaddition (CuAAC) was demonstrated. First, a PEGMA and MMA based block copolymer carrying multiple side-chain acetylene moieties on the hydrophobic segment for postfunctionalization was carried out. This involves the synthesis of a series of P(HEMA-co-MMA) random copolymers to be employed as macroinitiators in the controlled synthesis of P(HEMA-co-M...

  19. In vitro drug release and biological evaluation of biomimetic polymeric micelles self-assembled from amphiphilic deoxycholic acid–phosphorylcholine–chitosan conjugate

    International Nuclear Information System (INIS)

    Wu, Minming; Guo, Kai; Dong, Hongwei; Zeng, Rong; Tu, Mei; Zhao, Jianhao

    2014-01-01

    Novel biomimetic amphiphilic chitosan derivative, deoxycholic acid–phosphorylcholine–chitosan conjugate (DCA–PCCs) was synthesized based on the combination of Atherton–Todd reaction for coupling phosphorylcholine (PC) and carbodiimide coupling reaction for linking deoxycholic acid (DCA) to chitosan. The chemical structure of DCA–PCCs was characterized by 1 H and 31 P nuclear magnetic resonance (NMR). The self-assembly of DCA–PCCs in water was analyzed by fluorescence measurements, dynamic laser light-scattering (DLS), zeta potential and transmission electron microscopy (TEM) technologies. The results confirmed that the amphiphilic DCA–PCCs can self-assemble to form nanosized spherical micelles with biomimetic PC shell. In vitro biological evaluation revealed that DCA–PCCs micelles had low toxicity against NIH/3T3 mouse embryonic fibroblasts as well as good hemocompatibility. Using quercetin as a hydrophobic model drug, drug loading and release study suggested that biomimetic DCA–PCCs micelles could be used as a promising nanocarrier avoiding unfavorable biological response for hydrophobic drug delivery applications. - Highlights: • DCA–PCCs with phosphorylcholine and deoxycholic acid was synthesized. • DCA–PCCs can self-assemble to form spherical micelles in aqueous system. • DCA–PCCs micelles had excellent cytocompatibility and hemocompatibility. • DCA–PCCs micelles loaded with quercetin exhibited a sustained drug release behavior

  20. In vitro drug release and biological evaluation of biomimetic polymeric micelles self-assembled from amphiphilic deoxycholic acid–phosphorylcholine–chitosan conjugate

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Minming; Guo, Kai; Dong, Hongwei; Zeng, Rong, E-mail: tzengronga@jnu.edu.cn; Tu, Mei; Zhao, Jianhao

    2014-12-01

    Novel biomimetic amphiphilic chitosan derivative, deoxycholic acid–phosphorylcholine–chitosan conjugate (DCA–PCCs) was synthesized based on the combination of Atherton–Todd reaction for coupling phosphorylcholine (PC) and carbodiimide coupling reaction for linking deoxycholic acid (DCA) to chitosan. The chemical structure of DCA–PCCs was characterized by {sup 1}H and {sup 31}P nuclear magnetic resonance (NMR). The self-assembly of DCA–PCCs in water was analyzed by fluorescence measurements, dynamic laser light-scattering (DLS), zeta potential and transmission electron microscopy (TEM) technologies. The results confirmed that the amphiphilic DCA–PCCs can self-assemble to form nanosized spherical micelles with biomimetic PC shell. In vitro biological evaluation revealed that DCA–PCCs micelles had low toxicity against NIH/3T3 mouse embryonic fibroblasts as well as good hemocompatibility. Using quercetin as a hydrophobic model drug, drug loading and release study suggested that biomimetic DCA–PCCs micelles could be used as a promising nanocarrier avoiding unfavorable biological response for hydrophobic drug delivery applications. - Highlights: • DCA–PCCs with phosphorylcholine and deoxycholic acid was synthesized. • DCA–PCCs can self-assemble to form spherical micelles in aqueous system. • DCA–PCCs micelles had excellent cytocompatibility and hemocompatibility. • DCA–PCCs micelles loaded with quercetin exhibited a sustained drug release behavior.

  1. Farnesylthiosalicylic acid-loaded lipid-polyethylene glycol-polymer hybrid nanoparticles for treatment of glioblastoma.

    Science.gov (United States)

    Kaffashi, Abbas; Lüle, Sevda; Bozdağ Pehlivan, Sibel; Sarısözen, Can; Vural, İmran; Koşucu, Hüsnü; Demir, Taner; Buğdaycı, Kadir Emre; Söylemezoğlu, Figen; Karlı Oğuz, Kader; Mut, Melike

    2017-08-01

    We aimed to develop lipid-polyethylene glycol (PEG)-polymer hybrid nanoparticles, which have high affinity to tumour tissue with active ingredient, a new generation antineoplastic drug, farnesylthiosalicylic acid (FTA) for treatment of glioblastoma. Farnesylthiosalicylic acid-loaded poly(lactic-co-glycolic acid)-1,2 distearoyl-glycerol-3-phospho-ethanolamine-N [methoxy (PEG)-2000] ammonium salt (PLGA-DSPE-PEG) with or without 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) hybrid nanoparticles has been prepared and evaluated for in-vitro characterization. Cytotoxicity of FTA-loaded nanoparticles along with its efficacy on rat glioma-2 (RG2) cells was also evaluated both in vitro (in comparison with non-malignant cell line, L929) and in vivo. Scanning electron microscopy studies showed that all formulations prepared had smooth surface and spherical in shape. FTA and FTA-loaded nanoparticles have cytotoxic activity against RG2 glioma cell lines in cell culture studies, which further increases with addition of DOTAP. Magnetic resonance imaging and histopathologic evaluation on RG2 tumour cells in rat glioma model (49 female Wistar rats, 250-300 g) comparing intravenous and intratumoral injections of the drug have been performed and FTA-loaded nanoparticles reduced tumour size significantly in in-vivo studies, with higher efficiency of intratumoral administration than intravenous route. Farnesylthiosalicylic acid-loaded PLGA-DSPE-PEG-DOTAP hybrid nanoparticles are proven to be effective against glioblastoma in both in-vitro and in-vivo experiments. © 2017 Royal Pharmaceutical Society.

  2. Smart pH- and reduction-dual-responsive folate-PEG-coated polymeric lipid vesicles for tumor-triggered targeted drug delivery

    Science.gov (United States)

    Wang, Sheng; Wang, Hanjie; Liu, Zhongyun; Wang, Liangliang; Wang, Xiaomin; Su, Lin; Chang, Jin

    2014-06-01

    To improve their therapeutic index, designed nanocarriers should preferentially accumulate in tumor tissues and then rapidly enter tumor cells to release the encapsulated drugs in a triggered manner. In this article, a new kind of a smart pH- and reduction-dual-responsive drug delivery system based on folate-PEG-coated polymeric lipid vesicles (FPPLVs) formed from amphiphilic dextran derivatives was designed and prepared successfully. PEG chains with pH-sensitive hydrazone bonds, stearyl alcohol (SA) chains with reduction-sensitive disulfide bonds and folate were connected to a dextran main chain. The newly developed FPPLVs had a nano-sized structure (~50 nm) with a PEG coating. The in vitro DOX release profiles showed that the FPPLVs achieved a triggered drug release in response to acidic pH and reducing environments due to the cleavage of hydrazone bonds and disulfide bonds. It has also been demonstrated by an in vitro cellular uptake study that the FPPLVs lose their PEG coating as well as expose the folate in acidic conditions, which allows them to efficiently enter tumor cells through ligand-receptor interactions. In vitro cytotoxicity measurements also confirmed that FPPLVs exhibited pronounced antitumor activity against HeLa cells. These results suggest that FPPLVs are promising carriers for smart antitumor drug delivery applications.To improve their therapeutic index, designed nanocarriers should preferentially accumulate in tumor tissues and then rapidly enter tumor cells to release the encapsulated drugs in a triggered manner. In this article, a new kind of a smart pH- and reduction-dual-responsive drug delivery system based on folate-PEG-coated polymeric lipid vesicles (FPPLVs) formed from amphiphilic dextran derivatives was designed and prepared successfully. PEG chains with pH-sensitive hydrazone bonds, stearyl alcohol (SA) chains with reduction-sensitive disulfide bonds and folate were connected to a dextran main chain. The newly developed FPPLVs had a

  3. Poly(Acrylic Acid-b-Styrene) Amphiphilic Multiblock Copolymers as Building Blocks for the Assembly of Discrete Nanoparticles

    Science.gov (United States)

    Greene, Anna C.; Zhu, Jiahua; Pochan, Darrin J.; Jia, Xinqiao; Kiick, Kristi L.

    2011-01-01

    In order to expand the utility of current polymeric micellar systems, we have developed amphiphilic multiblock copolymers containing alternating blocks of poly(acrylic acid) and poly(styrene). Heterotelechelic poly(tert-butyl acrylate-b-styrene) diblock copolymers containing an α-alkyne and an ω-azide were synthesized by atom transfer radical polymerization (ATRP), allowing control over the molecular weight while maintaining narrow polydispersity indices. The multiblock copolymers were constructed by copper-catalyzed azide-alkyne cycloaddition of azide-alkyne end functional diblock copolymers which were then characterized by 1H NMR, FT-IR and SEC. The tert-butyl moieties of the poly(tert-butyl acrylate-b-styrene) multiblock copolymers were easily removed to form the poly(acrylic acid-b-styrene) multiblock copolymer ((PAA-PS)9), which contained up to 9 diblock repeats. The amphiphilic multiblock (PAA-PS)9 (Mn = 73.3 kg/mol) was self-assembled by dissolution into tetrahydrofuran and extensive dialysis against deionized water for 4 days. The critical micelle concentration (CMC) for (PAA-PS)9 was determined by fluorescence spectroscopy using pyrene as a fluorescent probe and was found to be very low at 2 × 10-4 mg/mL. The (PAA-PS)9 multiblock was also analyzed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The hydrodynamic diameter of the particles was found to be 11 nm. Discrete spherical particles were observed by TEM with an average particle diameter of 14 nm. The poly(acrylic acid) periphery of the spherical particles should allow for future conjugation of biomolecules. PMID:21552373

  4. Protein-lipid interactions at interfaces

    Directory of Open Access Journals (Sweden)

    Wilde, P.

    2000-04-01

    Full Text Available Foams and emulsions are both types of multiphase foods and are a dispersion of one immiscible phase (e.g. air or oil in another (e.g. water. Amphiphilic molecules (either proteins or chemical compounds are able to stabilise the interface between these phases and are termed emulsifiers. The ability of protein emulsifiers to bind lipid is reviewed, and the mechanisms underlying the behaviour of these and low molecular weight surfactants (LMWS at the interface are summarised. New research, exploiting atomic force microscopy, has given fresh insights into the mechanisms by which proteins and LMWS interact when both are present at the interface, compromising the stability of foams and emulsions stabilised by these mixtures. The understanding of component interactions at the interfacial level is essential if advances are to be made in the control and manipulation of multiphase foods during production and storage.Las espumas y las emulsiones son dispersiones de una fase inmiscible (ejemplo aire o aceite en otra (ejemplo agua. Las moléculas anfifílicas (bien proteínas o compuestos químicos pueden estabilizar la interfase y se denominan emulsionantes. En este artículo se revisa la habilidad de los emulsionantes proteínicos para enlazar lípidos y los mecanismos que subyacen en el comportamiento de estas moléculas así como de los tensioactivos de bajo peso molecular en la interfase. Recientes investigaciones que usan la microscopía han ofrecido visiones nuevas de los mecanismos mediante los cuales las proteínas y los tensioactivos de bajo peso molecular interaccionan cuando ambos están presentes en la interfase, comprometiendo la estabilidad de espumas y emulsiones estabilizadas por estas mezclas. El entendimiento de las interacciones entre componentes a nivel interfacial es esencial para lograr avances en el control y manipulación de alimentos multifases durante la producción y el almacenamiento.

  5. Lipophilisation de composés phénoliques par voie enzymatique et propriétés antioxydantes des molécules lipophilisées

    Directory of Open Access Journals (Sweden)

    Javier Lopez-Giraldo Luis

    2007-01-01

    Full Text Available The oxidative modification of lipids in foods and cosmetics may lead to alteration of their qualities and can have physiopathological repercussion on consumer. To counteract these inauspicious effects, phenolic compounds, derived from plants, such as phenolic acids and flavonoids seem to be particularly promising. However, their relatively low solubility in apolar media limits their application in oil-based products. In emulsion, thanks to their water-solubility, these compounds are located in aqueous compartment, whereas lipid peroxidation occurs at the oil-water interface. Therefore, there is an interest in trying to enhance the amphiphilic character of phenolic antioxidants by enzymatic lipophilization which corresponds to the grafting of an aliphatic chain (fatty alcohol, acid or amine through lipase-catalysed esterification or amidation reactions. Due to its amphiphilic nature, the resulting functionalized antioxidant would accumulate at the oil-water interface, increasing protection of target-lipids from oxidation. Various operational conditions and strategies can be adopted to perform lipase-mediated hydrophobation with high yields. This paper firstly presents a panorama of the advances in this field. Finally, the antioxidant capacity of lipophilized compounds is reviewed and compared with that of the native molecule.

  6. Glycosyl-Nucleolipids as new bioinspired amphiphiles.

    Science.gov (United States)

    Latxague, Laurent; Patwa, Amit; Amigues, Eric; Barthélémy, Philippe

    2013-09-30

    Four new Glycosyl-NucleoLipid (GNL) analogs featuring either a single fluorocarbon or double hydrocarbon chains were synthesized in good yields from azido thymidine as starting material. Physicochemical studies (surface tension measurements, differential scanning calorimetry) indicate that hydroxybutanamide-based GNLs feature endothermic phase transition temperatures like the previously reported double chain glycerol-based GNLs. The second generation of GNFs featuring a free nucleobase reported here presents a better surface activity (lower glim) compared to the first generation of GNFs.

  7. Modeling growth, lipid accumulation and lipid turnover in submerged batch cultures of Umbelopsis isabellina

    NARCIS (Netherlands)

    Meeuwse, P.; Akbari, P.; Tramper, J.; Rinzema, A.

    2012-01-01

    The production of lipids by oleaginous yeast and fungi becomes more important because these lipids can be used for biodiesel production. To understand the process of lipid production better, we developed a model for growth, lipid production and lipid turnover in submerged batch fermentation. This

  8. Characterization of the N-terminal segment used by the barley yellow dwarf virus movement protein to promote interaction with the nuclear membrane of host plant cells.

    Science.gov (United States)

    Dennison, Sarah Rachel; Harris, Frederick; Brandenburg, Klaus; Phoenix, David Andrew

    2007-11-01

    The barley yellow dwarf virus movement protein (BYDV-MP) requires its N-terminal sequence to promote the transport of viral RNA into the nuclear compartment of host plant cells. Here, graphical analysis predicts that this sequence would form a membrane interactive amphiphilic alpha-helix. Confirming this prediction, NT1, a peptide homologue of the BYDV-MP N-terminal sequence, was found to be alpha-helical (65%) in the presence of vesicles mimics of the nuclear membrane. The peptide increased the fluidity of these nuclear membrane mimics (rise in wavenumber of circa 0.5-1.0 cm(-1)) and induced surface pressure changes of 2 mN m(-1) in lipid monolayers with corresponding compositions. Taken with isotherm analysis these results suggest that BYDV-MP forms an N-terminal amphiphilic alpha-helix, which partitions into the nuclear membrane primarily through thermodynamically stable associations with the membrane lipid headgroup region. We speculate that these associations may play a role in targeting of the nuclear membrane by BYDM-MP.

  9. Unraveling lipid metabolism in lipid-dependent pathogenic Malassezia yeasts

    OpenAIRE

    Celis Ramirez, A.M.

    2017-01-01

    Malassezia yeasts are lipid-dependent fungal species that are common members of the human and animal skin microbiota. The lipid-dependency is a crucial trait in the adaptation process to grow on the skin but also plays a role in their pathogenic life style. Malassezia species can cause several skin infections like dandruff or seborrheic dermatitis but also bloodstream infections. Understanding the lipid metabolism in Malassezia is essential to understand its life style as skin commensal and p...

  10. Vaccine Adjuvant Incorporation Strategy Dictates Peptide Amphiphile Micelle Immunostimulatory Capacity.

    Science.gov (United States)

    Zhang, Rui; Kramer, Jake S; Smith, Josiah D; Allen, Brittany N; Leeper, Caitlin N; Li, Xiaolei; Morton, Logan D; Gallazzi, Fabio; Ulery, Bret D

    2018-06-01

    Current vaccine research has shifted from traditional vaccines (i.e., whole-killed or live-attenuated) to subunit vaccines (i.e., protein, peptide, or DNA) as the latter is much safer due to delivering only the bioactive components necessary to produce a desirable immune response. Unfortunately, subunit vaccines are very weak immunogens requiring delivery vehicles and the addition of immunostimulatory molecules termed adjuvants to convey protective immunity. An interesting type of delivery vehicle is peptide amphiphile micelles (PAMs), unique biomaterials where the vaccine is part of the nanomaterial itself. Due to the modularity of PAMs, they can be readily modified to deliver both vaccine antigens and adjuvants within a singular construct. Through the co-delivery of a model antigenic epitope (Ovalbumin 319-340 -OVA BT ) and a known molecular adjuvant (e.g., 2,3-dipalmitoyl-S-glyceryl cysteine-Pam 2 C), greater insight into the mechanisms by which PAMs can exert immunostimulatory effects was gained. It was found that specific combinations of antigen and adjuvant can significantly alter vaccine immunogenicity both in vitro and in vivo. These results inform fundamental design rules that can be leveraged to fabricate optimal PAM-based vaccine formulations for future disease-specific applications. Graphical Abstract.

  11. Lipid polymorphism and the functional roles of lipids in biological membranes

    NARCIS (Netherlands)

    Cullis, P.R.; Kruijff, B. de

    1979-01-01

    The reasons for the great variety of lipids found in biological membranes, and the relations between lipid composition and membrane function pose major unsolved problems in membrane biology. Perhaps the only major functional role of lipids which may be regarded as firmly established involves the

  12. Lysosomal lipid storage diseases.

    Science.gov (United States)

    Schulze, Heike; Sandhoff, Konrad

    2011-06-01

    Lysosomal lipid storage diseases, or lipidoses, are inherited metabolic disorders in which typically lipids accumulate in cells and tissues. Complex lipids, such as glycosphingolipids, are constitutively degraded within the endolysosomal system by soluble hydrolytic enzymes with the help of lipid binding proteins in a sequential manner. Because of a functionally impaired hydrolase or auxiliary protein, their lipid substrates cannot be degraded, accumulate in the lysosome, and slowly spread to other intracellular membranes. In Niemann-Pick type C disease, cholesterol transport is impaired and unesterified cholesterol accumulates in the late endosome. In most lysosomal lipid storage diseases, the accumulation of one or few lipids leads to the coprecipitation of other hydrophobic substances in the endolysosomal system, such as lipids and proteins, causing a "traffic jam." This can impair lysosomal function, such as delivery of nutrients through the endolysosomal system, leading to a state of cellular starvation. Therapeutic approaches are currently restricted to mild forms of diseases with significant residual catabolic activities and without brain involvement.

  13. Perspectives on marine zooplankton lipids

    DEFF Research Database (Denmark)

    Kattner, G.; Hagen, W.; Lee, R.F.

    2007-01-01

    We developed new perspectives to identify important questions and to propose approaches for future research on marine food web lipids. They were related to (i) structure and function of lipids, (ii) lipid changes during critical life phases, (iii) trophic marker lipids, and (iv) potential impact...... of climate change. The first addresses the role of lipids in membranes, storage lipids, and buoyancy with the following key question: How are the properties of membranes and deposits affected by the various types of lipids? The second deals with the importance of various types of lipids during reproduction......, development, and resting phases and addresses the role of the different storage lipids during growth and dormancy. The third relates to trophic marker lipids, which are an important tool to follow lipid and energy transfer through the food web. The central question is how can fatty acids be used to identify...

  14. Reversible photocontrol of molecular assemblies of metal complex containing azo-amphiphiles

    International Nuclear Information System (INIS)

    Einaga, Yasuaki; Mikami, Rie; Akitsu, Takashiro; Li, Guangming

    2005-01-01

    Photo-controllable molecular systems, [M(en) 2 ][Pt(en) 2 Cl 2 ](1) 4 (M 2+ =Pt 2+ , Pd 2+ and en=ethylenediamine), have been designed by the self-assembly of chloride-bridged platinum/palladium complexes and photochromic amphiphiles of the azobenzene derivative, 4-[4-(N-methyl-N-n-dodecylamino)phenylazo]benzene sulfonic acid (designated as compound 1). Reversible structural changes caused by cis-trans photoisomerization of azo groups in compound 1 were observed by alternating illumination of UV and visible light. Visible illumination resulted in the formation of the plate-like structures, whereas UV illumination resulted in fragmentation of the assembling structures. Reversible changes were observed in the electronic states of the chloride-bridged platinum/palladium complexes; the plate-like structures exhibited charge transfer absorption of chloride-bridged platinum complexes and delocalized Pt(II)/Pt(IV) states, while the fragments of the separated complexes exhibited no charge transfer bands. As a consequence, we have discovered that the reversible structural changes in this system could be controlled by photoillumination

  15. The FDA approved PI3K inhibitor GDC-0941 enhances in vitro the anti-neoplastic efficacy of Axitinib against c-myc-amplified high-risk medulloblastoma.

    Science.gov (United States)

    Ehrhardt, Michael; Craveiro, Rogerio B; Velz, Julia; Olschewski, Martin; Casati, Anna; Schönberger, Stefan; Pietsch, Torsten; Dilloo, Dagmar

    2018-04-01

    Aberrant receptor kinase signalling and tumour neovascularization are hallmarks of medulloblastoma development and are both considered valuable therapeutic targets. In addition to VEGFR1/2, expression of PDGFR α/β in particular has been documented as characteristic of metastatic disease correlating with poor prognosis. Therefore, we have been suggested that the clinically approved multi-kinase angiogenesis inhibitor Axitinib, which specifically targets these kinases, might constitute a promising option for medulloblastoma treatment. Indeed, our results delineate anti-neoplastic activity of Axitinib in medulloblastoma cell lines modelling the most aggressive c-myc-amplified Non-WNT/Non-SHH and SHH-TP53-mutated tumours. Exposure of medulloblastoma cell lines to Axitinib results in marked inhibition of proliferation and profound induction of cell death. The differential efficacy of Axitinib is in line with target expression of medulloblastoma cells identifying VEGFR 1/2, PDGFR α/β and c-kit as potential markers for drug application. The high specificity of Axitinib and the consequential low impact on the haematopoietic and immune system render this drug ideal multi-modal treatment approaches. In this context, we demonstrate that the clinically available PI3K inhibitor GDC-0941 enhances the anti-neoplastic efficacy of Axitinib against c-myc-amplified medulloblastoma. Our findings provide a rational to further evaluate Axitinib alone and in combination with other therapeutic agents for the treatment of most aggressive medulloblastoma subtypes. © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  16. Glycosyl-Nucleolipids as New Bioinspired Amphiphiles

    Directory of Open Access Journals (Sweden)

    Philippe Barthélémy

    2013-09-01

    Full Text Available Four new Glycosyl-NucleoLipid (GNL analogs featuring either a single fluorocarbon or double hydrocarbon chains were synthesized in good yields from azido thymidine as starting material. Physicochemical studies (surface tension measurements, differential scanning calorimetry indicate that hydroxybutanamide-based GNLs feature endothermic phase transition temperatures like the previously reported double chain glycerol-based GNLs. The second generation of GNFs featuring a free nucleobase reported here presents a better surface activity (lower glim compared to the first generation of GNFs.

  17. The emerging role of antineoplastic agents in the treatment of keloids and hypertrophic scars: a review.

    Science.gov (United States)

    Shridharani, Sachin M; Magarakis, Michael; Manson, Paul N; Singh, Navin K; Basdag, Basak; Rosson, Gedge D

    2010-03-01

    The management of keloids and hypertrophic scars continues to challenge health-care providers. Though both forms of pathologic scarring are distinct entities at the macro and microscopic level, their etiologies and treatment are often similar. Potential treatment approaches are progressing, and combinations of treatment options have been proposed in the literature with promising outcomes. The treatment evolution has reached a level where molecular therapeutic modalities are being investigated. Currently, no gold standard treatment exists. Overall success rates and patient satisfaction seem to be slowly climbing, but additional investigational studies must continue to be performed. Several studies have investigated antineoplastic agents, and there seems to be a marked improvement in rates of recurrence, patient satisfaction, and overall quality of scar when these agents are used. Intralesional injection and/or wound irrigation with interferon-a2b, interferon-g, mitomycin-C, bleomycin, or 5-fluorouracil seems to have a positive effect on the reduction of pathologic scars. There is mounting evidence that these drugs used alone or in combination therapy, have the potential to be an integral part of the treatment paradigm for hypertrophic scars and keloids.

  18. Incorporation of liquid lipid in lipid nanoparticles for ocular drug delivery enhancement

    International Nuclear Information System (INIS)

    Shen Jie; Sun Minjie; Ping Qineng; Ying Zhi; Liu Wen

    2010-01-01

    The present work investigates the effect of liquid lipid incorporation on the physicochemical properties and ocular drug delivery enhancement