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Sample records for 750-labeled phospholipid micelles

  1. Near infrared planar tumor imaging and quantification using nanosized Alexa 750-labeled phospholipid micelles

    Directory of Open Access Journals (Sweden)

    Aristarchos Papagiannaros

    2009-05-01

    Full Text Available Aristarchos Papagiannaros, Amit Kale, Tatyana S Levchenko, Dmitry Mongayt, William C Hartner, Vladimir P TorchilinDepartment of Pharmaceutical Sciences and Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, MA, USAAbstract: A novel highly biocompatible near infrared nanosized contrast agent was developed and used for rapid tumor detection and quantification using planar optical imaging and analysis. With this in mind, the near infrared fluorescent dye Alexa 750 was covalently attached to polyethylene glycol-phosphatidylethanolamine (PEG-PE conjugate, and double labeled (with Alexa and rhodamine PEG-PE micelles were injected into mice and observed using planar optical imaging. Pixel intensity data from the tumor site were normalized versus the autofluorescence of the animal at the same time point and normalized as signal to noise over the scattered light from the various tissues of the mice. The detected signal from the tumor was higher than the background noise allowing for rapid detection of the tumor. The tumor was clearly visible within one hour. Some signal was also detected from the abdomen of the mice. As determined by microscopy analysis, other organs of accumulation were the liver and kidney, which corresponded well to the data from the whole body imaging animal studies.Keywords: nanotechnology, nanomedicine, cancer imaging agents, near infrared imaging, micelles

  2. Near infrared planar tumor imaging and quantification using nanosized Alexa 750-labeled phospholipid micelles

    Science.gov (United States)

    Papagiannaros, Aristarchos; Kale, Amit; Levchenko, Tatyana S; Mongayt, Dmitry; Hartner, William C; Torchilin, Vladimir P

    2009-01-01

    A novel highly biocompatible near infrared nanosized contrast agent was developed and used for rapid tumor detection and quantification using planar optical imaging and analysis. With this in mind, the near infrared fluorescent dye Alexa 750 was covalently attached to polyethylene glycol-phosphatidylethanolamine (PEG-PE) conjugate, and double labeled (with Alexa and rhodamine) PEG-PE micelles were injected into mice and observed using planar optical imaging. Pixel intensity data from the tumor site were normalized versus the autofluorescence of the animal at the same time point and normalized as signal to noise over the scattered light from the various tissues of the mice. The detected signal from the tumor was higher than the background noise allowing for rapid detection of the tumor. The tumor was clearly visible within one hour. Some signal was also detected from the abdomen of the mice. As determined by microscopy analysis, other organs of accumulation were the liver and kidney, which corresponded well to the data from the whole body imaging animal studies. PMID:19516891

  3. Bile Salt Micelles and Phospholipid Vesicles Present in Simulated and Human Intestinal Fluids

    DEFF Research Database (Denmark)

    Elvang, Philipp A; Hinna, Askell H; Brouwers, Joachim;

    2016-01-01

    Knowledge about colloidal assemblies present in human intestinal fluids (HIFs), such as bile salt micelles and phospholipid vesicles, is regarded of importance for a better understanding of the in vivo dissolution and absorption behavior of poorly soluble drugs (Biopharmaceutics Classification...

  4. Effect of Vesicle-to-Micelle Transition on the Interactions of Phospholipid/Sodium Cholate Mixed Systems with Curcumin in Aqueous Solution.

    Science.gov (United States)

    Zhang, Sha; Wang, Xiaoyong

    2016-08-01

    The role of vesicle-to-micelle transition has been investigated in the interactions of phospholipid vesicles, phospholipid/sodium cholate (NaC) mixed vesicles, and phospholipid/NaC mixed micelles with curcumin in aqueous solution. The addition of NaC causes phospholipid vesicles to transit into phospholipid/NaC mixed vesicles and phospholipid/NaC mixed micelles. Turbidity measurement reveals that the presence of curcumin increases the NaC concentration for the solubilization of phospholipid vesicles, which indicates that the bound curcumin tends to suppress the vesicle-to-micelle transition. The pyrene polarity index and curcumin fluorescence anisotropy measurements suggest that phospholipid/NaC mixed micelles have a more compact structure than that of phospholipid vesicles and phospholipid/NaC mixed vesicles. Curcumin associated with phospholipid vesicles, phospholipid/NaC mixed vesicles, and phospholipid/NaC mixed micelles often results in higher intensities of absorption and fluorescence than those of free curcumin. However, phospholipid/NaC mixed vesicles lead to the highest values of absorption and fluorescence intensities, binding constant, and radical-scavenging capacity with curcumin. The different structures in the phospholipid bilayer of phospholipid/NaC mixed vesicles and the hydrophobic part of phospholipid/NaC mixed micelles where curcumin located are discussed to explain the interaction behaviors of phospholipid/NaC mixed systems with curcumin.

  5. Effect of Vesicle-to-Micelle Transition on the Interactions of Phospholipid/Sodium Cholate Mixed Systems with Curcumin in Aqueous Solution.

    Science.gov (United States)

    Zhang, Sha; Wang, Xiaoyong

    2016-08-01

    The role of vesicle-to-micelle transition has been investigated in the interactions of phospholipid vesicles, phospholipid/sodium cholate (NaC) mixed vesicles, and phospholipid/NaC mixed micelles with curcumin in aqueous solution. The addition of NaC causes phospholipid vesicles to transit into phospholipid/NaC mixed vesicles and phospholipid/NaC mixed micelles. Turbidity measurement reveals that the presence of curcumin increases the NaC concentration for the solubilization of phospholipid vesicles, which indicates that the bound curcumin tends to suppress the vesicle-to-micelle transition. The pyrene polarity index and curcumin fluorescence anisotropy measurements suggest that phospholipid/NaC mixed micelles have a more compact structure than that of phospholipid vesicles and phospholipid/NaC mixed vesicles. Curcumin associated with phospholipid vesicles, phospholipid/NaC mixed vesicles, and phospholipid/NaC mixed micelles often results in higher intensities of absorption and fluorescence than those of free curcumin. However, phospholipid/NaC mixed vesicles lead to the highest values of absorption and fluorescence intensities, binding constant, and radical-scavenging capacity with curcumin. The different structures in the phospholipid bilayer of phospholipid/NaC mixed vesicles and the hydrophobic part of phospholipid/NaC mixed micelles where curcumin located are discussed to explain the interaction behaviors of phospholipid/NaC mixed systems with curcumin. PMID:27403579

  6. Ultrafast vibrational dynamics of water confined in phospholipid reverse micelles

    Directory of Open Access Journals (Sweden)

    Elsaesser T.

    2013-03-01

    Full Text Available We study the ultrafast dynamics of OH stretching and bending vibrations of water inside dioleoylphosphatidylcholine (DOPC reverse micelles in a wide range of hydration. A strong hydration level dependence for the spectral diffusion rates is found and explained by the distinctly different environment for single water molecules bound to the anionic phosphate group. We show that the energy relaxation pathway of the OH stretching vibration at low hydration level involves the OH bending.

  7. Fluorine-18-labeled phospholipid quantum dot micelles for in vivo multimodal imaging from whole body to cellular scales

    International Nuclear Information System (INIS)

    We have designed new nano-probes applicable for both positron emission tomography (PET) and optical fluorescence in vivo imaging. Fluorine-18, which is commonly used for clinical imaging, has been coupled to phospholipid quantum dot (QD) micelles. This probe was injected in mice and we demonstrated that its dynamic quantitative whole body biodistribution and pharmacokinetics could be monitored using PET as well as the kinetics of their cellular uptake using in vivo fibered confocal fluorescence imaging. Phospholipid micelle encapsulation of QDs provides a highly versatile surface chemistry to conjugate multiple chemicals and biomolecules with controlled QD: molecule valency. Here, we show that, in contrast with several previous studies using other QD polymer coatings, these phospholipid QD micelles exhibit long circulation half-time in the blood stream (on the order of 2 h) and slow uptake by reticulo-endothelial system. (authors)

  8. Bile salt/phospholipid mixed micelle precursor pellets prepared by fluid-bed coating

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    Dong F

    2013-04-01

    Full Text Available Fuxia Dong,1,2 Yunchang Xie,1 Jianping Qi,1 Fuqiang Hu,3 Yi Lu,1 Sanming Li,2 Wei Wu1 1School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery of Ministry of Education and PLA, Shanghai, People’s Republic of China; 2School of Pharmacy, Shenyang Pharmaceutical University, Liaoning, People’s Republic of China; 3School of Pharmacy, Zhejiang University, Hangzhou, People’s Republic of China Abstract: Bile salt/phospholipid mixed micelles (MMs are potent carriers used for oral absorption of drugs that are poorly soluble in water; however, there are many limitations associated with liquid formulations. In the current study, the feasibility of preparing bile salt/phospholipid MM precursor (preMM pellets with high oral bioavailability, using fluid-bed coating technology, was examined. In this study, fenofibrate (FB and sodium deoxycholate (SDC were used as the model drug and the bile salt, respectively. To prepare the MMs and to serve as the micellular carrier, a weight ratio of 4:6 was selected for the sodium deoxycholate/phospholipids based on the ternary phase diagram. Polyethylene glycol (PEG 6000 was selected as the dispersion matrix for precipitation of the MMs onto pellets, since it can enhance the solubilizing ability of the MMs. Coating of the MMs onto the pellets using the fluid-bed coating technology was efficient and the pellets were spherical and intact. MMs could be easily reconstituted from preMM pellets in water. Although they existed in a crystalline state in the preMM pellets, FB could be encapsulated into the reconstituted MMs, and the MMs were redispersed better than solid dispersion pellets (FB:PEG = 1:3 and Lipanthyl®. The redispersibility of the preMM pellets increased with the increase of the FB/PEG/micellar carrier. PreMM pellets with a FB:PEG:micellar carrier ratio of 1:1.5:1.5 showed 284% and 145% bioavailability relative to Lipanthyl® and solid dispersion pellets (FB:PEG = 1:3, respectively. Fluid

  9. Self-Assembling Micelle-like Nanoparticles Based on Phospholipid-Polyethyleneimine Conjugates for Systemic Gene Delivery

    Science.gov (United States)

    Ko, Young Tag; Kale, Amit; Hartner, William C.; Papahadjopoulos-Sternberg, Brigitte; Torchilin, Vladimir P.

    2011-01-01

    With few exceptions, where local administration is feasible, progress towards broad clinical application of gene therapies requires the development of effective delivery systems. Here we report a novel non-viral gene delivery vector, ‘micelle-like nanoparticle’ (MNP) suitable for systemic application. MNP were engineered by condensing plasmid DNA with a chemical conjugate of phospholipid with polyethylenimine (PLPEI) and then coating the complexes with an envelope of lipid monolayer additionally containing polyethylene glycol-phosphatidyl ethanolamine (PEG-PE), resulting in spherical ‘hard-core’ nanoparticles loaded with DNA. MNP allowed for complete protection of the loaded DNA from enzymatic degradation, resistance to salt-induced aggregation, and reduced cytotoxicity. MNP also demonstrated prolonged blood circulation and low RES accumulation. Intravenous injection of MNP loaded with plasmid DNA encoding for the Green Fluorescence Protein (GFP) resulted in an effective transfection of a distal tumor. Thus, MNP provide a promising tool for systemic gene therapy. PMID:18929605

  10. Exposure to Iron Oxide Nanoparticles Coated with Phospholipid-Based Polymeric Micelles Induces Biochemical and Histopathological Pulmonary Changes in Mice

    Science.gov (United States)

    Radu (Balas), Mihaela; Din (Popescu), Ioana Mihaela; Hermenean, Anca; Cinteză, Otilia Ludmila; Burlacu, Radu; Ardelean, Aurel; Dinischiotu, Anca

    2015-01-01

    The biochemical and histopathological changes induced by the exposure to iron oxide nanoparticles coated with phospholipid-based polymeric micelles (IONPs-PM) in CD-1 mice lungs were analyzed. After 2, 3, 7 and 14 days following the intravenous injection of IONPs-PM (5 and 15 mg Fe/kg bw), lactate dehydrogenase (LDH) activity, oxidative stress parameters and the expression of Bax, Bcl-2, caspase-3 and TNF-α were evaluated in lung tissue. An increase of catalase (CAT) and glutathione reductase (GR) activities on the second day followed by a decrease on the seventh day, as well as a decline of lactate dehydrogenase (LDH), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity on the third and seventh day were observed in treated groups vs. controls. However, all these enzymatic activities almost fully recovered on the 14th day. The reduced glutathione (GSH) and protein thiols levels decreased significantly in nanoparticles-treated groups and remained diminished during the entire experimental period; by contrast malondialdehyde (MDA) and protein carbonyls increased between the 3rd and 14th day of treatment vs. control. Relevant histopathological modifications were highlighted using Hematoxylin and Eosin (H&E) staining. In addition, major changes in the expression of apoptosis markers were observed in the first week, more pronounced for the higher dose. The injected IONPs-PM generated a dose-dependent decrease of the mouse lung capacity, which counteracted oxidative stress, thus creating circumstances for morphopathological lesions and oxidation processes. PMID:26690409

  11. Development and evaluation of vitamin E d-α-tocopheryl polyethylene glycol 1000 succinate-mixed polymeric phospholipid micelles of berberine as an anticancer nanopharmaceutical.

    Science.gov (United States)

    Shen, Roger; Kim, Jane J; Yao, Mingyi; Elbayoumi, Tamer A

    2016-01-01

    Berberine (Brb) is an active alkaloid occurring in various common plant species, with well-recognized potential for cancer therapy. Brb not only augments the efficacy of antineoplastic chemotherapy and radiotherapy but also exhibits direct antimitotic and proapoptotic actions, along with distinct antiangiogenic and antimetastatic activities in a variety of tumors. Despite its low systemic toxicity, several pharmaceutical challenges limit the application of Brb in cancer therapy (ie, extremely low solubility and permeability, very poor pharmacokinetics (PKs), and oral bioavailability). Among lipid-based nanocarriers investigated recently for Brb, stealth amphiphilic micelles of polymeric phospholipid conjugates were studied here as a promising strategy to improve Brb delivery to tumors. Specifically, physicochemically stable micelles made of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000] (PEG-PE) mixed with d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) (PEG-succinate ester of vitamin E), in a 3:1 M ratio, increased Brb solubilization by 300%. Our PEG-PE/TPGS-mixed micelles firmly retained the incorporated Brb, displaying extended-release profile in simulated media, with up to 30-fold projected improvement in simulated PKs of Brb. Owing to the markedly better uptake of Brb-containing mixed micelles in vitro, our Brb-mixed micelles nanoformulation significantly amplified apoptosis and overall cytotoxic effectiveness against monolayer and spheroid cultures of human prostate carcinomas (16- to 18-fold lower half-maximal inhibitory concentration values in PC3 and LNPaC, respectively), compared to free Brb. Mixed PEG-PE/TPGS micelles represent a promising delivery platform for the sparingly soluble anticancer agent, Brb, encouraging further pharmaceutical development of this drug for cancer therapy. PMID:27217747

  12. Correlation of insulin-enhancing properties of vanadium-dipicolinate complexes in model membrane systems: phospholipid langmuir monolayers and AOT reverse micelles.

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    Sostarecz, Audra G; Gaidamauskas, Ernestas; Distin, Steve; Bonetti, Sandra J; Levinger, Nancy E; Crans, Debbie C

    2014-04-22

    We explore the interactions of V(III) -, V(IV) -, and V(V) -2,6-pyridinedicarboxylic acid (dipic) complexes with model membrane systems and whether these interactions correlate with the blood-glucose-lowering effects of these compounds on STZ-induced diabetic rats. Two model systems, dipalmitoylphosphatidylcholine (DPPC) Langmuir monolayers and AOT (sodium bis(2-ethylhexyl)sulfosuccinate) reverse micelles present controlled environments for the systematic study of these vanadium complexes interacting with self-assembled lipids. Results from the Langmuir monolayer studies show that vanadium complexes in all three oxidation states interact with the DPPC monolayer; the V(III) -phospholipid interactions result in a slight decrease in DPPC molecular area, whereas V(IV) and V(V) -phospholipid interactions appear to increase the DPPC molecular area, an observation consistent with penetration into the interface of this complex. Investigations also examined the interactions of V(III) - and V(IV) -dipic complexes with polar interfaces in AOT reverse micelles. Electron paramagnetic resonance spectroscopic studies of V(IV) complexes in reverse micelles indicate that the neutral and smaller 1:1 V(IV) -dipic complex penetrates the interface, whereas the larger 1:2 V(IV) complex does not. UV/Vis spectroscopy studies of the anionic V(III) -dipic complex show only minor interactions. These results are in contrast to behavior of the V(V) -dipic complex, [VO2 (dipic)](-) , which penetrates the AOT/isooctane reverse micellar interface. These model membrane studies indicate that V(III) -, V(IV) -, and V(V) -dipic complexes interact with and penetrate the lipid interfaces differently, an effect that agrees with the compounds' efficacy at lowering elevated blood glucose levels in diabetic rats. PMID:24615733

  13. 21 CFR 358.750 - Labeling of drug products for the control of dandruff, seborrheic dermatitis, or psoriasis.

    Science.gov (United States)

    2010-04-01

    ... dandruff, seborrheic dermatitis, or psoriasis. 358.750 Section 358.750 Food and Drugs FOOD AND DRUG... Dermatitis, and Psoriasis § 358.750 Labeling of drug products for the control of dandruff, seborrheic dermatitis, or psoriasis. (a) Statement of identity. The labeling of the product contains the...

  14. Application of spray granulation for conversion of mixed phospholipid-bile salt micelles to dry powder form: influence of drug hydrophobicity on nanoparticle reagglomeration

    Directory of Open Access Journals (Sweden)

    Lv QY

    2014-01-01

    Full Text Available Qingyuan Lv,1 Xianyi Li,2 Baode Shen,1 He Xu,1 Chengying Shen,1 Ling Dai,1 Jinxia Bai,1 Hailong Yuan,1 Jin Han11Department of Pharmacy, 302 Military Hospital, 2Institute for Drug and Instrument Control, Health Department, General Logistics Department of People's Liberation Army, Beijing, People's Republic of ChinaAbstract: The aim of this study was to investigate the feasibility of using spray granulation as a drying method to convert phospholipid (PL-sodium deoxycholate (SDC-mixed micelles (MMs containing a water-insoluble drug to a solid dosage form and to evaluate how drugs with significantly different physicochemical properties affect the spray granulation process and subsequent in vitro and in vivo processes. Cucurbitacin B (Cu B and glycyrrhizin (GL were used as the model drugs. After spray granulation, the dried Cu B-PL/SDC-MM powder was completely redispersible within 15 minutes in vitro. Meanwhile, the area under the curve during 24 hours (AUC0–24 and peak serum concentration from the dried powder were significantly (P<0.05 lower than the values from Cu B-PL/SDC-MMs in vivo. However, a better result was obtained for GL, ie, the drug was redispersed completely within 5 minutes in vitro. Further, absorption from the dried GL-PL/SDC-MM powder was increased to the same level as that for GL-PL/SDC-MMs in vivo compared with the control group. The difference in these results can be found in Cu B and GL. Cu B nanoparticles reagglomerated when released, resulting in slower redispersibility and less absorption compared with the original PL-SDC-MMs. However, no agglomeration or delay was observed for GL. A possible explanation is the difference in surface hydrophobicity between Cu B and GL. The results of this study not only show that spray granulation is an effective drying technique that can complement spray-drying and freeze-drying, but also confirm that the physicochemical properties of a drug have a significant influence on the in vitro and

  15. Polymeric micelles containing reversibly phospholipid-modified anti-survivin siRNA: a promising strategy to overcome drug resistance in cancer.

    Science.gov (United States)

    Salzano, G; Riehle, R; Navarro, G; Perche, F; De Rosa, G; Torchilin, V P

    2014-02-28

    The discovery that survivin, a small anti-apoptotic protein, is involved in chemoresistance, opens a new scenario to overcome the drug resistance in cancer. It was shown that siRNA can efficiently inhibit the expression of survivin in cancer cells. However, the clinical use of siRNA is still hampered by an unfavorable pharmacokinetic profile. To address this problem, earlier we developed a novel system to deliver siRNA into cancer cells. Namely, we reversibly modified the survivin siRNA with a phosphothioethanol (PE) portion via a reducible disulfide bond and incorporated the resulting siRNA-S-S-PE conjugate into nanosized polyethyelene glycol 2000-phosphatidyl ethanolamine (PEG2000-PE)-based polymeric micelles (PM), obtaining survivin siRNA PM. The activity of these nanopreparations was evaluated by survivin protein down-regulation, tumor cell growth inhibition, and chemosensitization of the treated tumor cells to paclitaxel (PXL). We found a significant decrease of cell viability and down-regulation of survivin protein levels after treatment with survivin siRNA PM in several cancer cell lines. In addition, the down-regulation of survivin by treating cells with survivin siRNA PM, elicited a significant sensitization of the cells to PXL, in both sensitive and resistant cancer cell lines. Finally, we demonstrated successful co-delivery of PXL and survivin siRNA in the same PM leading to superior therapeutic activity compared to their sequential administration. Our results support the use of this new platform for the treatment of the most aggressive tumors. PMID:24099916

  16. Micelles Hydrodynamics

    CERN Document Server

    Svintradze, David V

    2016-01-01

    A micelle consists of monolayer of lipid molecules containing hydrophilic head and hydrophobic tail. These amphiphilic molecules in aqueous environment aggregate spontaneously into monomolecular layer held together due to hydrophobic effect by weak non-covalent forces. Micelles are flexible surfaces that show variety of shapes of different topology, but remarkably in mechanical equilibrium conditions they are spherical in shape. The shape and size of a micelle are functions of many variables such as lipid concentration, temperature, ionic strength, etc. Addressing the question, why the shape of micelles is sphere in mechanical equilibrium conditions, analytically proved to be a difficult problem. In the following paper we offer the shortest and elegant analytical proof of micelles spheroidal nature when they are thermodynamically equilibrated with solvent. The formalism presented in this paper can be readily extended to any homogenous surfaces, such are vesicles and membranes.

  17. Janus Micelles

    OpenAIRE

    Erhardt, R.; Böker, A.; Zettl, H; H. KAYA; PYCKHOUT-HINTZEN, W.; Krausch, G.; Abetz, V.; A. Müller

    2001-01-01

    A novel strategy to synthesize amphiphilic surface-compartmentalized nanoparticles based on linear ABC triblock copolymers is presented. These so-called Janus micelles consist of a cross-linked core and a corona with a "northern" and a "southern" hemisphere. Selectively cross-linking spherical domains of the polybutadiene middle block in a well-ordered bulk morphology of a polystyrene-block-polybutadiene-block-poly( methyl methacrylate) triblock copolymer (SBM) leads to the conservation of th...

  18. Bactericidal block copolymer micelles.

    Science.gov (United States)

    Vyhnalkova, Renata; Eisenberg, Adi; van de Ven, Theo

    2011-05-12

    Block copolymer micelles with bactericidal properties were designed to deactivate pathogens such as E. coli bacteria. The micelles of PS-b-PAA and PS-b-P4VP block copolymers were loaded with biocides TCMTB or TCN up to 20 or 30 wt.-%, depending on the type of antibacterial agent. Bacteria were exposed to loaded micelles and bacterial deactivation was evaluated. The micelles loaded with TCN are bactericidal; bacteria are killed in less than two minutes of exposure. The most likely interpretation of the data is that the biocide is transferred to the bacteria by repeated micelle/bacteria contacts, and not via the solution. PMID:21275041

  19. Lipid metabolizing enzyme activities modulated by phospholipid substrate lateral distribution.

    Science.gov (United States)

    Salinas, Dino G; Reyes, Juan G; De la Fuente, Milton

    2011-09-01

    Biological membranes contain many domains enriched in phospholipid lipids and there is not yet clear explanation about how these domains can control the activity of phospholipid metabolizing enzymes. Here we used the surface dilution kinetic theory to derive general equations describing how complex substrate distributions affect the activity of enzymes following either the phospholipid binding kinetic model (which assumes that the enzyme molecules directly bind the phospholipid substrate molecules), or the surface-binding kinetic model (which assumes that the enzyme molecules bind to the membrane before binding the phospholipid substrate). Our results strongly suggest that, if the enzyme follows the phospholipid binding kinetic model, any substrate redistribution would increase the enzyme activity over than observed for a homogeneous distribution of substrate. Besides, enzymes following the surface-binding model would be independent of the substrate distribution. Given that the distribution of substrate in a population of micelles (each of them a lipid domain) should follow a Poisson law, we demonstrate that the general equations give an excellent fit to experimental data of lipases acting on micelles, providing reasonable values for kinetic parameters--without invoking special effects such as cooperative phenomena. Our theory will allow a better understanding of the cellular-metabolism control in membranes, as well as a more simple analysis of the mechanisms of membrane acting enzymes. PMID:21108012

  20. The aminosterol antibiotic squalamine permeabilizes large unilamellar phospholipid vesicles.

    Science.gov (United States)

    Selinsky, B S; Zhou, Z; Fojtik, K G; Jones, S R; Dollahon, N R; Shinnar, A E

    1998-03-13

    structures release from the bilayers and aggregate to form either new vesicles or squalamine/phospholipid mixed micelles. PMID:9545568

  1. In Vitro Evaluation of Theranostic Polymeric Micelles for Imaging and Drug Delivery in Cancer

    OpenAIRE

    Kumar, Rajiv; Kulkarni, Apurva; Nagesha, Dattatri K; Sridhar, Srinivas

    2012-01-01

    For the past decade engineered nanoplatforms have seen a momentous progress in developing a multimodal theranostic formulation which can be simultaneously used for imaging and therapy. In this report we describe the synthesis and application of theranostic phospholipid based polymeric micelles for optical fluorescence imaging and controlled drug delivery. CdSe quantum dots (QDs) and anti-cancer drug, doxorubicin (Dox), were co-encapsulated into the hydrophobic core of the micelles. The micell...

  2. New self-assembled nanocrystal micelles for biolabels and biosensors.

    Energy Technology Data Exchange (ETDEWEB)

    Tallant, David Robert; Wilson, Michael C. (University of New Mexico, Albuquerque, NM); Leve, Erik W. (University of New Mexico, Albuquerque, NM); Fan, Hongyou; Brinker, C. Jeffrey; Gabaldon, John (University of New Mexico, Albuquerque, NM); Scullin, Chessa (University of New Mexico, Albuquerque, NM)

    2005-12-01

    The ability of semiconductor nanocrystals (NCs) to display multiple (size-specific) colors simultaneously during a single, long term excitation holds great promise for their use in fluorescent bio-imaging. The main challenges of using nanocrystals as biolabels are achieving biocompatibility, low non-specific adsorption, and no aggregation. In addition, functional groups that can be used to further couple and conjugate with biospecies (proteins, DNAs, antibodies, etc.) are required. In this project, we invented a new route to the synthesis of water-soluble and biocompatible NCs. Our approach is to encapsulate as-synthesized, monosized, hydrophobic NCs within the hydrophobic cores of micelles composed of a mixture of surfactants and phospholipids containing head groups functionalized with polyethylene glycol (-PEG), -COOH, and NH{sub 2} groups. PEG provided biocompatibility and the other groups were used for further biofunctionalization. The resulting water-soluble metal and semiconductor NC-micelles preserve the optical properties of the original hydrophobic NCs. Semiconductor NCs emit the same color; they exhibit equal photoluminescence (PL) intensity under long-time laser irradiation (one week) ; and they exhibit the same PL lifetime (30-ns). The results from transmission electron microscopy and confocal fluorescent imaging indicate that water-soluble semiconductor NC-micelles are biocompatible and exhibit no aggregation in cells. We have extended the surfactant/lipid encapsulation techniques to synthesize water-soluble magnetic NC-micelles. Transmission electron microscopy results suggest that water-soluble magnetic NC-micelles exhibit no aggregation. The resulting NC-micelles preserve the magnetic properties of the original hydrophobic magnetic NCs. Viability studies conducted using yeast cells suggest that the magnetic nanocrystal-micelles are biocompatible. We have demonstrated, for the first time, that using external oscillating magnetic fields to manipulate

  3. Complex coacervate core micelles.

    Science.gov (United States)

    Voets, Ilja K; de Keizer, Arie; Cohen Stuart, Martien A

    2009-01-01

    In this review we present an overview of the literature on the co-assembly of neutral-ionic block, graft, and random copolymers with oppositely charged species in aqueous solution. Oppositely charged species include synthetic (co)polymers of various architectures, biopolymers - such as proteins, enzymes and DNA - multivalent ions, metallic nanoparticles, low molecular weight surfactants, polyelectrolyte block copolymer micelles, metallo-supramolecular polymers, equilibrium polymers, etcetera. The resultant structures are termed complex coacervate core/polyion complex/block ionomer complex/interpolyelectrolyte complex micelles (or vesicles); i.e., in short C3Ms (or C3Vs) and PIC, BIC or IPEC micelles (and vesicles). Formation, structure, dynamics, properties, and function will be discussed. We focus on experimental work; theory and modelling will not be discussed. Recent developments in applications and micelles with heterogeneous coronas are emphasized.

  4. Enhanced incorporation of dietary DHA into lymph phospholipids by altering its molecular carrier.

    Science.gov (United States)

    Subbaiah, Papasani V; Dammanahalli, Karigowda J; Yang, Peng; Bi, Jian; O'Donnell, J Michael

    2016-08-01

    Several previous studies indicated that for optimal uptake by the brain, docosahexaenoic acid (DHA) should be present as phospholipid in the plasma. However most of dietary DHA is absorbed as triacylglycerol (TAG) because it is released as free fatty acid during digestion of either TAG-DHA (fish oil) or sn-2-DHA phospholipid (krill oil), and subsequently incorporated into TAG of chylomicrons. We tested the hypothesis that the absorption of DHA as phospholipid can be increased if it is present in the sn-1 position of dietary phospholipid or in lysophosphatidylcholine (LPC), because it would escape the hydrolysis by pancreatic phospholipase A2. We infused micelle containing the DHA either as LPC or as free acid, into the duodenum of lymph cannulated rats, and analyzed the chylomicrons and HDL of the lymph for the DHA-containing lipids. The results show that while the total amount of DHA absorbed was comparable from the two types of micelle, the percentage of DHA recovered in lymph phospholipids was 5 times greater with LPC-DHA, compared to free DHA. Furthermore, the amount of DHA recovered in lymph HDL was increased by 2-fold when LPC-DHA micelle was infused. These results could potentially lead to a novel strategy to increase brain DHA levels through the diet. PMID:27178174

  5. Development of Polysorbate 80/Phospholipid mixed micellar formation for docetaxel and assessment of its in vivo distribution in animal models

    Science.gov (United States)

    Song, Hua; Geng, Hongquan; Ruan, Jing; Wang, Kan; Bao, Chenchen; Wang, Juan; Peng, Xia; Zhang, Xueqing; Cui, Daxiang

    2011-04-01

    Docetaxel (DTX) is a very important member of taxoid family. Despite several alternative delivery systems reported recently, DTX formulated by Polysorbate 80 and alcohol (Taxotere®) is still the most frequent administration in clinical practice. In this study, we incorporated DTX into Polysorbate 80/Phospholipid mixed micelles and compared its structural characteristics, pharmacokinetics, biodistribution, and blood compatibility with its conventional counterparts. Results showed that the mixed micelles loaded DTX possessed a mean size of approximately 13 nm with narrow size distribution and a rod-like micelle shape. In the pharmacokinetics assessment, there was no significant difference between the two preparations ( P > 0.05), which demonstrated that the DTX in the two preparations may share a similar pharmacokinetic process. However, the Polysorbate 80/Phospholipid mixed micelles can increase the drug residence amount of DTX in kidney, spleen, ovary and uterus, heart, and liver. The blood compatibility assessment study revealed that the mixed micelles were safe for intravenous injection. In conclusion, Polysorbate 80/Phospholipid mixed micelle is safe, can improve the tumor therapeutic effects of DTX in the chosen organs, and may be a potential alternative dosage form for clinical intravenous administration of DTX.

  6. Molecular dynamics simulations of the helical antimicrobial peptide ovispirin-1 in a zwitterionic dodecylphosphocholine micelle

    DEFF Research Database (Denmark)

    Khandelia, Himanshu; Kaznessis, Yiannis N

    2005-01-01

    We have carried out a 40-ns all-atom molecular dynamics simulation of the helical antimicrobial peptide ovispirin-1 (OVIS) in a zwitterionic diphosphocholine (DPC) micelle. The DPC micelle serves as an economical and effective model for a cellular membrane owing to the presence of a choline...... headgroup, which resembles those of membrane phospholipids. OVIS, which was initially placed along a micelle diameter, diffuses out to the water-DPC interface, and the simulation stabilizes to an interface-bound steady state in 40 ns. The helical content of the peptide marginally increases in the process....... The final conformation, orientation, and the structure of OVIS are in excellent agreement with the experimentally observed properties of the peptide in the presence of lipid bilayers composed of 75% zwitterionic lipids. The amphipathic peptide binds to the micelle with its hydrophobic face buried...

  7. Surfactant phospholipid metabolism.

    Science.gov (United States)

    Agassandian, Marianna; Mallampalli, Rama K

    2013-03-01

    Pulmonary surfactant is essential for life and is composed of a complex lipoprotein-like mixture that lines the inner surface of the lung to prevent alveolar collapse at the end of expiration. The molecular composition of surfactant depends on highly integrated and regulated processes involving its biosynthesis, remodeling, degradation, and intracellular trafficking. Despite its multicomponent composition, the study of surfactant phospholipid metabolism has focused on two predominant components, disaturated phosphatidylcholine that confers surface-tension lowering activities, and phosphatidylglycerol, recently implicated in innate immune defense. Future studies providing a better understanding of the molecular control and physiological relevance of minor surfactant lipid components are needed. This article is part of a Special Issue entitled Phospholipids and Phospholipid Metabolism. PMID:23026158

  8. Mammalian P4-ATPases and ABC transporters and their role in phospholipid transport.

    Science.gov (United States)

    Coleman, Jonathan A; Quazi, Faraz; Molday, Robert S

    2013-03-01

    Transport of phospholipids across cell membranes plays a key role in a wide variety of biological processes. These include membrane biosynthesis, generation and maintenance of membrane asymmetry, cell and organelle shape determination, phagocytosis, vesicle trafficking, blood coagulation, lipid homeostasis, regulation of membrane protein function, apoptosis, etc. P(4)-ATPases and ATP binding cassette (ABC) transporters are the two principal classes of membrane proteins that actively transport phospholipids across cellular membranes. P(4)-ATPases utilize the energy from ATP hydrolysis to flip aminophospholipids from the exocytoplasmic (extracellular/lumen) to the cytoplasmic leaflet of cell membranes generating membrane lipid asymmetry and lipid imbalance which can induce membrane curvature. Many ABC transporters play crucial roles in lipid homeostasis by actively transporting phospholipids from the cytoplasmic to the exocytoplasmic leaflet of cell membranes or exporting phospholipids to protein acceptors or micelles. Recent studies indicate that some ABC proteins can also transport phospholipids in the opposite direction. The importance of P(4)-ATPases and ABC transporters is evident from the findings that mutations in many of these transporters are responsible for severe human genetic diseases linked to defective phospholipid transport. This article is part of a Special Issue entitled Phospholipids and Phospholipid Metabolism.

  9. Polymerization of anionic wormlike micelles.

    Science.gov (United States)

    Zhu, Zhiyuan; González, Yamaira I; Xu, Hangxun; Kaler, Eric W; Liu, Shiyong

    2006-01-31

    Polymerizable anionic wormlike micelles are obtained upon mixing the hydrotropic salt p-toluidine hydrochloride (PTHC) with the reactive anionic surfactant sodium 4-(8-methacryloyloxyoctyl)oxybenzene sulfonate (MOBS). Polymerization captures the cross-sectional radius of the micelles (approximately 2 nm), induces micellar growth, and leads to the formation of a stable single-phase dispersion of wormlike micellar polymers. The unpolymerized and polymerized micelles were characterized using static and dynamic laser light scattering, small-angle neutron scattering, 1H NMR, and stopped-flow light scattering. Stopped-flow light scattering was also used to measure the average lifetime of the unpolymerized wormlike micelles. A comparison of the average lifetime of unpolymerized wormlike micelles with the surfactant monomer propagation rate was used to elucidate the mechanism of polymerization. There is a significant correlation between the ratio of the average lifetime to the monomer propagation rate and the average aggregation number of the polymerized wormlike micelles. PMID:16430253

  10. Equation of State for Phospholipid Self-Assembly

    DEFF Research Database (Denmark)

    Marsh, Derek

    2016-01-01

    Phospholipid self-assembly is the basis of biomembrane stability. The entropy of transfer from water to self-assembled micelles of lysophosphatidylcholines and diacyl phosphatidylcholines with different chain lengths converges to a common value at a temperature of 44°C. The corresponding enthalpies...... of transfer converge at ∼-18°C. An equation of state for the free energy of self-assembly formulated from this thermodynamic data depends on the heat capacity of transfer as the sole parameter needed to specify a particular lipid. For lipids lacking calorimetric data, measurement of the critical...

  11. Surfactant phospholipid metabolism

    OpenAIRE

    Agassandian, Marianna; Mallampalli, Rama K.

    2012-01-01

    Pulmonary surfactant is essential for life and is comprised of a complex lipoprotein-like mixture that lines the inner surface of the lung to prevent alveolar collapse at the end of expiration. The molecular composition of surfactant depends on highly integrated and regulated processes involving its biosynthesis, remodeling, degradation, and intracellular trafficking. Despite its multicomponent composition, the study of surfactant phospholipid metabolism has focused on two predominant compone...

  12. Enzyme recovery using reversed micelles.

    NARCIS (Netherlands)

    Dekker, M.

    1990-01-01

    The objective of this study was to develop a liquid-liquid extraction process for the recovery of extracellular enzymes. The potentials of reaching this goal by using reversed micelles in an organic solvent have been investigated.Reversed micelles are aggregates of surfactant molecules containing an

  13. In Vitro Evaluation of Theranostic Polymeric Micelles for Imaging and Drug Delivery in Cancer

    Directory of Open Access Journals (Sweden)

    Rajiv Kumar, Apurva Kulkarni, Dattatri K Nagesha, Srinivas Sridhar

    2012-01-01

    Full Text Available For the past decade engineered nanoplatforms have seen a momentous progress in developing a multimodal theranostic formulation which can be simultaneously used for imaging and therapy. In this report we describe the synthesis and application of theranostic phospholipid based polymeric micelles for optical fluorescence imaging and controlled drug delivery. CdSe quantum dots (QDs and anti-cancer drug, doxorubicin (Dox, were co-encapsulated into the hydrophobic core of the micelles. The micelles are characterized using optical spectroscopy for characteristic absorbance and fluorescence features of QDs and Dox. TEM and DLS studies yielded a size of <50 nm for the micellar formulations with very narrow size distribution. A sustained release of the drug was observed from the co-encapsulated micellar formulation. In vitro optical fluorescence imaging and cytotoxicity studies with HeLa cell line demonstrated the potential of these micellar systems as efficient optical imaging and therapeutic probes.

  14. Tetracycline diffusion through phospholipid bilayers and binding to phospholipids.

    OpenAIRE

    Argast, M; Beck, C.F.

    1984-01-01

    The ability of tetracycline to pass through phospholipid bilayers by diffusion was investigated. Liposomes did not retain enclosed tetracycline. Accumulation of tetracycline was observed with liposomes containing entrapped Tet repressor protein. These results indicate that the drug can pass through lipid bilayers. The antibiotic was also shown to bind to liposomes and isolated phospholipids.

  15. Glycation Reactions of Casein Micelles.

    Science.gov (United States)

    Moeckel, Ulrike; Duerasch, Anja; Weiz, Alexander; Ruck, Michael; Henle, Thomas

    2016-04-13

    After suspensions of micellar casein or nonmicellar sodium caseinate had been heated, respectively, in the presence and absence of glucose for 0-4 h at 100 °C, glycation compounds were quantitated. The formation of Amadori products as indicators for the "early" Maillard reaction were in the same range for both micellar and nonmicellar caseins, indicating that reactive amino acid side chains within the micelles are accessible for glucose in a comparable way as in nonmicellar casein. Significant differences, however, were observed concerning the formation of the advanced glycation end products (AGEs), namely, N(ε)-carboxymethyllysine (CML), pyrraline, pentosidine, and glyoxal-lysine dimer (GOLD). CML could be observerd in higher amounts in nonmicellar casein, whereas in the micelles the pyrraline formation was increased. Pentosidine and GOLD were formed in comparable amounts. Furthermore, the extent of protein cross-linking was significantly higher in the glycated casein micelles than in the nonmicellar casein samples. Dynamic light scattering and scanning electron microscopy showed that glycation has no influence on the size of the casein micelles, indicating that cross-linking occurs only in the interior of the micelles, but altered the surface morphology. Studies on glycation and nonenzymatic cross-linking can contribute to the understanding of the structure of casein micelles. PMID:27018258

  16. Phospholipid profiles of Clostridium difficile.

    OpenAIRE

    Drucker, D B; Wardle, H. M.; Boote, V.

    1996-01-01

    Phospholipid molecular species present in 32 isolates of Clostridium difficile were examined by fast atom bombardment-mass spectrometry in negative-ion mode. This revealed major anions consistent with the expected presence of the following phosphatidylglycerol (PG) analogs: PG(31:2), PG(32:1), PG(33:2), PG(33:1), PG(34:2), and PG(34:1). The major phospholipid molecular species are distinct from those of other bacterial groups examined.

  17. Cell signalling and phospholipid metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Boss, W.F.

    1990-01-01

    These studies explored whether phosphoinositide (PI) has a role in plants analogous to its role in animal cells. Although no parallel activity of PI in signal transduction was found in plant cells, activity of inositol phospholipid kinase was found to be modulated by light and by cell wall degrading enzymes. These studies indicate a major role for inositol phospholipids in plant growth and development as membrane effectors but not as a source of second messengers.

  18. Micelle Structure and Hydrophobic Hydration.

    Science.gov (United States)

    Long, Joshua A; Rankin, Blake M; Ben-Amotz, Dor

    2015-08-26

    Despite the ubiquity and utility of micelles self-assembled from aqueous surfactants, longstanding questions remain regarding their surface structure and interior hydration. Here we combine Raman spectroscopy with multivariate curve resolution (Raman-MCR) to probe the hydrophobic hydration of surfactants with various aliphatic chain lengths, and either anionic (carboxylate) or cationic (trimethylammonium) head groups, both below and above the critical micelle concentration. Our results reveal significant penetration of water into micelle interiors, well beyond the first few carbons adjacent to the headgroup. Moreover, the vibrational C-D frequency shifts of solubilized deuterated n-hexane confirm that it resides in a dry, oil-like environment (while the localization of solubilized benzene is sensitive to headgroup charge). Our findings imply that the hydrophobic core of a micelle is surrounded by a highly corrugated surface containing hydrated non-polar cavities whose depth increases with increasing surfactant chain length, thus bearing a greater resemblance to soluble proteins than previously recognized. PMID:26222042

  19. Dicarboxylic phospholipids and irradiated biomembranes

    International Nuclear Information System (INIS)

    It was decided to study the effects of ionizing radiations on biomembranes, with special reference to erythrocytes and liver microsomes representing two kinds of membrane very common in nature. Diacid phospholipids were observed at these membranes and the results are reported in part one of this work. It appeared essential to examine as far as possible the metabolism, in vitro and in animals, of these diacids and to find out whether certain harmful effects of radiations on the proteins (membrane permeability changes and enzyme inactivation) could be due to the action of these newly formed compounds. The study of acid compounds formed under irradiation was limited to nonanal-9-oic acid and azelaic acid. Part two deals with the incorporation of acid and diacid compounds into lipids and the effects of diacid phospholipids on the membrane permeability. A chapter is devoted to the changes in certain enzyme activities brought about by diacid phospholipids

  20. Ultrasound-Mediated Polymeric Micelle Drug Delivery.

    Science.gov (United States)

    Xia, Hesheng; Zhao, Yue; Tong, Rui

    2016-01-01

    The synthesis of multi-functional nanocarriers and the design of new stimuli-responsive means are equally important for drug delivery. Ultrasound can be used as a remote, non-invasive and controllable trigger for the stimuli-responsive release of nanocarriers. Polymeric micelles are one kind of potential drug nanocarrier. By combining ultrasound and polymeric micelles, a new modality (i.e., ultrasound-mediated polymeric micelle drug delivery) has been developed and has recently received increasing attention. A major challenge remaining in developing ultrasound-responsive polymeric micelles is the improvement of the sensitivity or responsiveness of polymeric micelles to ultrasound. This chapter reviews the recent advance in this field. In order to understand the interaction mechanism between ultrasound stimulus and polymeric micelles, ultrasound effects, such as thermal effect, cavitation effect, ultrasound sonochemistry (including ultrasonic degradation, ultrasound-initiated polymerization, ultrasonic in-situ polymerization and ultrasound site-specific degradation), as well as basic micellar knowledge are introduced. Ultrasound-mediated polymeric micelle drug delivery has been classified into two main streams based on the different interaction mechanism between ultrasound and polymeric micelles; one is based on the ultrasound-induced physical disruption of the micelle and reversible release of payload. The other is based on micellar ultrasound mechanochemical disruption and irreversible release of payload.

  1. Oxidative stability of marine phospholipids

    DEFF Research Database (Denmark)

    Lu, Henna Fung Sieng; Nielsen, Nina Skall; Baron, Caroline Pascale;

    Many studies have shown that marine phospholipids (MPL) provide more advantages than fish oil. They have better bioavailability, better resistance towards oxidation and higher content of eicosapentaenoic acids (EPA) and docosahexaenoic acids (DHA) than oily triglycerides (fish oil). The objective...... prepared in the form of emulsions by high pressure homogenizer. Then, the oxidative and hydrolytic stability of phospholipids was investigated by measurement of simple chemical analyses such as Peroxide Value and Free Fatty Acids, and 31PNMR after 32 days storage at 2ºC. The oxidative stability of MPL...... was further investigated through measurement of secondary volatile compounds by Solid Phase Microextraction at several time intervals. On the other hand, the Maillard reaction was investigated through the measurement of color changes and pyrrole content before and after 32 days storage. Preliminary result...

  2. Nanomechanics of electrospun phospholipid fiber

    Energy Technology Data Exchange (ETDEWEB)

    Mendes, Ana C., E-mail: anac@food.dtu.dk, E-mail: ioach@food.dtu.dk; Chronakis, Ioannis S., E-mail: anac@food.dtu.dk, E-mail: ioach@food.dtu.dk [Technical University of Denmark, DTU-Food, Søltofts Plads B227, DK-2800, Kgs. Lyngby (Denmark); Nikogeorgos, Nikolaos; Lee, Seunghwan [Department of Mechanical Engineering, Technical University of Denmark, DK-2800 Kgs. Lyngby (Denmark)

    2015-06-01

    Electrospun asolectin phospholipid fibers were prepared using isooctane as a solvent and had an average diameter of 6.1 ± 2.7 μm. Their mechanical properties were evaluated by nanoindentation using Atomic Force Microscopy, and their elastic modulus was found to be approximately 17.2 ± 1 MPa. At a cycle of piezo expansion-retraction (loading-unloading) of a silicon tip on a fiber, relatively high adhesion was observed during unloading. It is proposed that this was primarily due to molecular rearrangements at the utmost layers of the fiber caused by the indentation of the hydrophilic tip. The phospholipid fibers were shown to be stable in ambient conditions, preserving the modulus of elasticity up to 24 h.

  3. Stable Polymer Micelles Formed by Metal Coordination

    NARCIS (Netherlands)

    Wang, Junyou; Stuart, Martien A. Cohen; Marcelis, Antonius T. M.; Colomb-Delsuc, Mathieu; Otto, Sijbren; van der Gucht, Jasper

    2012-01-01

    Metal-containing polymer micelles have attracted much attention due to their potential for medical and nanotechnological applications. In this paper, we present a method to prepare stable metal-containing polymer micelles. A diblock copolymer poly(4-vinylpyridine)-b-poly(ethylene oxide) (P4VP(48)-b-

  4. Formation of micelles with complex coacervate cores.

    NARCIS (Netherlands)

    Cohen Stuart, M.A.; Besseling, N.A.M.; Fokkink, R.G.

    1998-01-01

    Micelles are commonly regarded as colloidal structures spontaneously formed by amphiphilic molecules, that is, molecules consisting of two distinct parts of which one is soluble and the other is insoluble. This definition is too restrictive: other kinds of molecules can also form micelles. We report

  5. Adsorption of ruthenium red to phospholipid membranes.

    OpenAIRE

    Voelker, D; Smejtek, P

    1996-01-01

    We have measured the distribution of the hexavalent ruthenium red cation (RuR) between water and phospholipid membranes, have shown the critical importance of membrane negative surface charge for RuR binding, and determined the association constant of RuR for different phospholipid bilayers. The studies were performed with liposomes made of mixtures of zwitterionic L-alpha-phosphatidylcholine (PC), and one of the negatively charged phospholipids: L-alpha-phosphatidylserine (PS), L-alpha-phosp...

  6. Casein micelle structure: a concise review

    Directory of Open Access Journals (Sweden)

    Chanokphat Phadungath

    2005-01-01

    Full Text Available Milk is a complex biological fluid with high amount of proteins, lipid and minerals. The function of milk is to supply nutrients such as essential amino acids required for the growth of the newborn. In addition, due to the importance of casein and casein micelles for the functional behavior of dairy products, the nature and structure of casein micelles have been studied extensively. However, the exact structure of casein micelles is still under debate. Various models for casein micelle structure have been proposed. Most of the proposedmodels fall into three general categories, which are: coat-core, subunit (sub-micelles, and internal structure models. The coat-core models, proposed by Waugh and Nobel in 1965, Payens in 1966, Parry and Carroll in 1969, and Paquin and co-workers in 1987, describe the micelle as an aggregate of caseins with outer layer differing in composition form the interior, and the structure of the inner part is not accurately identified. The sub-micelle models, proposed by Morr in 1967, Slattery and Evard in 1973, Schmidt in 1980, Walstra in1984, and Ono and Obata in 1989, is considered to be composed of roughly spherical uniform subunits. The last models, the internal structure models, which were proposed by Rose in 1969, Garnier and Ribadeau- Dumas in 1970, Holt in 1992, and Horne in 1998, specify the mode of aggregation of the different caseins.

  7. Dynamic Processes in Diblock Copolymer Micelles

    Science.gov (United States)

    Robertson, Megan; Singh, Avantika

    2013-03-01

    Diblock copolymers, which form micelle structures in selective solvents, offer advantages of robustness and tunability of micelle characteristics as compared to small molecule surfactants. Diblock copolymer micelles in water have been a subject of great interest in drug delivery applications based on their high loading capacity and targeted drug delivery. The aim of this work is to understand the dynamic processes which underlie the self-assembly of diblock copolymer micelle systems which have a semi-crystalline core. Due to the large size of the molecules, the self-assembly of block copolymer micelles occurs on significantly longer time scales than small molecule analogues. The present work focuses on amphiphilic diblock copolymers containing blocks of poly(ethylene oxide) (a hydrophilic polymer) and polycaprolactone (a hydrophobic, semi-crystalline polymer), which spontaneously self-assemble into spherical micelles in water. A variety of experimental techniques are used to probe the kinetic processes relevant to micelle self-assembly, including time-resolved neutron scattering, dynamic light scattering, pulsed field gradient nuclear magnetic resonance, and fluorescence resonance energy transfer experiments.

  8. Chemical reactions in reverse micelle systems

    Science.gov (United States)

    Matson, Dean W.; Fulton, John L.; Smith, Richard D.; Consani, Keith A.

    1993-08-24

    This invention is directed to conducting chemical reactions in reverse micelle or microemulsion systems comprising a substantially discontinuous phase including a polar fluid, typically an aqueous fluid, and a microemulsion promoter, typically a surfactant, for facilitating the formation of reverse micelles in the system. The system further includes a substantially continuous phase including a non-polar or low-polarity fluid material which is a gas under standard temperature and pressure and has a critical density, and which is generally a water-insoluble fluid in a near critical or supercritical state. Thus, the microemulsion system is maintained at a pressure and temperature such that the density of the non-polar or low-polarity fluid exceeds the critical density thereof. The method of carrying out chemical reactions generally comprises forming a first reverse micelle system including an aqueous fluid including reverse micelles in a water-insoluble fluid in the supercritical state. Then, a first reactant is introduced into the first reverse micelle system, and a chemical reaction is carried out with the first reactant to form a reaction product. In general, the first reactant can be incorporated into, and the product formed in, the reverse micelles. A second reactant can also be incorporated in the first reverse micelle system which is capable of reacting with the first reactant to form a product.

  9. Functional and structural stability of the epidermal growth factor receptor in detergent micelles and phospholipid nanodiscs

    DEFF Research Database (Denmark)

    Mi, Li-Zhi; Grey, Michael J; Nishida, Noritaka;

    2008-01-01

    Cellular signaling mediated by the epidermal growth factor receptor (EGFR or ErbB) family of receptor tyrosine kinases plays an important role in regulating normal and oncogenic cellular physiology. While structures of isolated EGFR extracellular domains and intracellular protein tyrosine kinase...... domains have suggested mechanisms for growth factor-mediated receptor dimerization and allosteric kinase domain activation, understanding how the transmembrane and juxtamembrane domains contribute to transmembrane signaling requires structural studies on intact receptor molecules. In this report......, recombinant EGFR constructs containing the extracellular, transmembrane, juxtamembrane, and kinase domains are overexpressed and purified from human embryonic kidney 293 cell cultures. The oligomerization state, overall structure, and functional stability of the purified EGF-bound receptor are characterized...

  10. Stabilization of functional recombinant cannabinoid receptor CB(2 in detergent micelles and lipid bilayers.

    Directory of Open Access Journals (Sweden)

    Krishna Vukoti

    Full Text Available Elucidation of the molecular mechanisms of activation of G protein-coupled receptors (GPCRs is among the most challenging tasks for modern membrane biology. For studies by high resolution analytical methods, these integral membrane receptors have to be expressed in large quantities, solubilized from cell membranes and purified in detergent micelles, which may result in a severe destabilization and a loss of function. Here, we report insights into differential effects of detergents, lipids and cannabinoid ligands on stability of the recombinant cannabinoid receptor CB(2, and provide guidelines for preparation and handling of the fully functional receptor suitable for a wide array of downstream applications. While we previously described the expression in Escherichia coli, purification and liposome-reconstitution of multi-milligram quantities of CB(2, here we report an efficient stabilization of the recombinant receptor in micelles - crucial for functional and structural characterization. The effects of detergents, lipids and specific ligands on structural stability of CB(2 were assessed by studying activation of G proteins by the purified receptor reconstituted into liposomes. Functional structure of the ligand binding pocket of the receptor was confirmed by binding of (2H-labeled ligand measured by solid-state NMR. We demonstrate that a concerted action of an anionic cholesterol derivative, cholesteryl hemisuccinate (CHS and high affinity cannabinoid ligands CP-55,940 or SR-144,528 are required for efficient stabilization of the functional fold of CB(2 in dodecyl maltoside (DDM/CHAPS detergent solutions. Similar to CHS, the negatively charged phospholipids with the serine headgroup (PS exerted significant stabilizing effects in micelles while uncharged phospholipids were not effective. The purified CB(2 reconstituted into lipid bilayers retained functionality for up to several weeks enabling high resolution structural studies of this GPCR at

  11. Ibuprofen induced drug loaded polymeric micelles

    Institute of Scientific and Technical Information of China (English)

    Song Wei Tan; Hong Jun Wang; Ke Hua Tu; Hong Liang Jiang; Li Qun Wang

    2011-01-01

    Three model drugs with different function groups were chosen to dialyze with dextran-graft-poly (N-isopropylacrylamide). Only ibuprofen could induce the formation of drug loaded micelles, which was confirmed with dynamic light scattering and transmission electron microscope. Hydrogen-bonding between the amide groups of poly (N-isopropylacrylamide) and the carboxyl groups of ibuprofen was driving force for the drug-loaded micelle. It was also found that the diameter of the ibuprofen-loaded micelles changed reversibly against temperature.

  12. Phospholipid liposomes functionalized by protein

    Science.gov (United States)

    Glukhova, O. E.; Savostyanov, G. V.; Grishina, O. A.

    2015-03-01

    Finding new ways to deliver neurotrophic drugs to the brain in newborns is one of the contemporary problems of medicine and pharmaceutical industry. Modern researches in this field indicate the promising prospects of supramolecular transport systems for targeted drug delivery to the brain which can overcome the blood-brain barrier (BBB). Thus, the solution of this problem is actual not only for medicine, but also for society as a whole because it determines the health of future generations. Phospholipid liposomes due to combination of lipo- and hydrophilic properties are considered as the main future objects in medicine for drug delivery through the BBB as well as increasing their bioavailability and toxicity. Liposomes functionalized by various proteins were used as transport systems for ease of liposomes use. Designing of modification oligosaccharide of liposomes surface is promising in the last decade because it enables the delivery of liposomes to specific receptor of human cells by selecting ligand and it is widely used in pharmacology for the treatment of several diseases. The purpose of this work is creation of a coarse-grained model of bilayer of phospholipid liposomes, functionalized by specific to the structural elements of the BBB proteins, as well as prediction of the most favorable orientation and position of the molecules in the generated complex by methods of molecular docking for the formation of the structure. Investigation of activity of the ligand molecule to protein receptor of human cells by the methods of molecular dynamics was carried out.

  13. Polysaccharide-Based Micelles for Drug Delivery

    Directory of Open Access Journals (Sweden)

    Nan Zhang

    2013-05-01

    Full Text Available Delivery of hydrophobic molecules and proteins has been an issue due to poor bioavailability following administration. Thus, micelle carrier systems are being investigated to improve drug solubility and stability. Due to problems with toxicity and immunogenicity, natural polysaccharides are being explored as substitutes for synthetic polymers in the development of new micelle systems. By grafting hydrophobic moieties to the polysaccharide backbone, self-assembled micelles can be readily formed in aqueous solution. Many polysaccharides also possess inherent bioactivity that can facilitate mucoadhesion, enhanced targeting of specific tissues, and a reduction in the inflammatory response. Furthermore, the hydrophilic nature of some polysaccharides can be exploited to enhance circulatory stability. This review will highlight the advantages of polysaccharide use in the development of drug delivery systems and will provide an overview of the polysaccharide-based micelles that have been developed to date.

  14. Micelle Catalysis of an Aromatic Substitution Reaction

    Science.gov (United States)

    Corsaro, Gerald; Smith J. K.

    1976-01-01

    Describes an experiment in which the iodonation of aniline reaction is shown to undergo catalysis in solution of sodium lauryl sulfate which forms micelles with negatively charged pseudo surfaces. (MLH)

  15. Patterning and characterization of model phospholipid membranes

    Science.gov (United States)

    Kassu, Aschalew; Calzzani, Fernando A., Jr.; Taguenang, Jean M.; Sileshi, Redahegn K.; Sharma, Anup

    2008-08-01

    Phospholipid, which is a building block of biological membranes, plays an important role in compartmentalization of cellular reaction environment and control of the physicochemical conditions inside the reaction environment. Phospholipid bilayer membrane has been proposed as a natural biocompatible platform for attaching biological molecules like proteins for biosensing related application. Due to the enormous potential applications of biomimetic model biomembranes, various techniques for depositions and patterning of these membranes onto solid supports and their possible biotechnological applications have been reported by different groups. In this work, patterning of phospholipid thin-films is accomplished by interferometric lithography as well as using lithographic masks in liquid phase. Surface Enhanced Raman Spectroscopy and Atomic Force microscopy are used to characterize the model phospholipid membrane and the patterning technique. We describe an easy and reproducible technique for direct patterning of azo-dye (NBD)-labeled phospholipid (phosphatidylcholine) in aqueous medium using a low-intensity 488 nm Ar+ laser and various kinds of lithographic masks.

  16. Polymeric micelles for acyclovir drug delivery.

    Science.gov (United States)

    Sawdon, Alicia J; Peng, Ching-An

    2014-10-01

    Polymeric prodrug micelles for delivery of acyclovir (ACV) were synthesized. First, ACV was used directly to initiate ring-opening polymerization of ɛ-caprolactone to form ACV-polycaprolactone (ACV-PCL). Through conjugation of hydrophobic ACV-PCL with hydrophilic methoxy poly(ethylene glycol) (MPEG) or chitosan, polymeric micelles for drug delivery were formed. (1)H NMR, FTIR, and gel permeation chromatography were employed to show successful conjugation of MPEG or chitosan to hydrophobic ACV-PCL. Through dynamic light scattering, zeta potential analysis, transmission electron microscopy, and critical micelle concentration (CMC), the synthesized ACV-tagged polymeric micelles were characterized. It was found that the average size of the polymeric micelles was under 200nm and the CMCs of ACV-PCL-MPEG and ACV-PCL-chitosan were 2.0mgL(-1) and 6.6mgL(-1), respectively. The drug release kinetics of ACV was investigated and cytotoxicity assay demonstrates that ACV-tagged polymeric micelles were non-toxic.

  17. Connexin channels and phospholipids: association and modulation

    Directory of Open Access Journals (Sweden)

    Harris Andrew L

    2009-08-01

    Full Text Available Abstract Background For membrane proteins, lipids provide a structural framework and means to modulate function. Paired connexin hemichannels form the intercellular channels that compose gap junction plaques while unpaired hemichannels have regulated functions in non-junctional plasma membrane. The importance of interactions between connexin channels and phospholipids is poorly understood. Results Endogenous phospholipids most tightly associated with purified connexin26 or connexin32 hemichannels or with junctional plaques in cell membranes, those likely to have structural and/or modulatory effects, were identified by tandem electrospray ionization-mass spectrometry using class-specific interpretative methods. Phospholipids were characterized by headgroup class, charge, glycerol-alkyl chain linkage and by acyl chain length and saturation. The results indicate that specific endogenous phospholipids are uniquely associated with either connexin26 or connexin32 channels, and some phospholipids are associated with both. Functional effects of the major phospholipid classes on connexin channel activity were assessed by molecular permeability of hemichannels reconstituted into liposomes. Changes to phospholipid composition(s of the liposome membrane altered the activity of connexin channels in a manner reflecting changes to the surface charge/potential of the membrane and, secondarily, to cholesterol content. Together, the data show that connexin26 and connexin32 channels have a preference for tight association with unique anionic phospholipids, and that these, independent of headgroup, have a positive effect on the activity of both connexin26 and connexin32 channels. Additionally, the data suggest that the likely in vivo phospholipid modulators of connexin channel structure-function that are connexin isoform-specific are found in the cytoplasmic leaflet. A modulatory role for phospholipids that promote negative curvature is also inferred. Conclusion

  18. Detection of hydrogen peroxide with chemiluminescent micelles

    Directory of Open Access Journals (Sweden)

    Dongwon Lee

    2008-08-01

    Full Text Available Dongwon Lee1, Venkata R Erigala1,3, Madhuri Dasari1, Junhua Yu2, Robert M Dickson2, Niren Murthy11The Wallace H. Coulter Department of Biomedical Engineering; 2Department of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA, USA; 3The Scripps Research Institute, La Jolla, CA, USAAbstract: The overproduction of hydrogen peroxide is implicated in the progress of numerous life-threatening diseases and there is a great need for the development of contrast agents that can detect hydrogen peroxide in vivo. In this communication, we present a new contrast agent for hydrogen peroxide, termed peroxalate micelles, which detect hydrogen peroxide through chemiluminescence, and have the physical/chemical properties needed for in vivo imaging applications. The peroxalate micelles are composed of amphiphilic peroxalate based copolymers and the fluorescent dye rubrene, they have a ‘stealth’ polyethylene glycol (PEG corona to evade macrophage phagocytosis, and a diameter of 33 nm to enhance extravasation into permeable tissues. The peroxalate micelles can detect nanomolar concentrations of hydrogen peroxide (>50 nM and thus have the sensitivity needed to detect physiological concentrations of hydrogen peroxide. We anticipate numerous applications of the peroxalate micelles for in vivo imaging of hydrogen peroxide, given their high sensitivity, small size, and biocompatible PEG corona.Keywords: hydrogen peroixde, chemiluminescence, micelles, amphiphilic copolymer

  19. Molecular Exchange in Ordered Diblock Copolymer Micelles

    Science.gov (United States)

    Choi, Soo-Hyung; Lodge, Timothy; Bates, Frank

    2011-03-01

    Previously, molecular exchange between spherical micelles in dilute solution (1 vol% polymer) was investigated using time-resolved small-angle neutron scattering (TR-SANS). As the concentration of spherical micelles formed by the diblock copolymers increases, the micelles begin to overlap and eventually pack onto body-centered cubic (BCC) lattice. In this study, concentrated, ordered micelles (15 vol% polymers) prepared by dispersing isotopically labeled poly(styrene- b -ethylene-alt-propylene) in an isotopic squalane mixture was investigated to understand the micellar concentration dependence of the molecular exchange. Perfectly random mixing of isotopically labeled micelles on the BCC lattice was confirmed by SANS patterns where the interparticle contribution vanishes, resulting in an intensity that directly relates to the exchange kinetics. The measured molecular exchange process for the concentrated, ordered system is qualitatively consistent with the previous observations, but the rate is more than an order of magnitude slower than that for the dilute, disordered system. Infineum(IPrime), MRSEC(NSF), NIST.

  20. Structural properties of self-assembled polymeric micelles

    DEFF Research Database (Denmark)

    Mortensen, K.

    1998-01-01

    At present, the thermodynamic understanding of complex copolymer systems is undergoing important developments. Block copolymers aggregate in selective solvents into micelles of various form and size depending on molecular architecture and interaction parameters. The micelles constitute the basis ...

  1. Efficient deacylation of N-acylimidazoles by functionalized surfactant micelles

    OpenAIRE

    Ihara, Yasuji; Nango, Mamoru; Koga, Joichi; ナンゴ, マモル; 南後, 守

    1989-01-01

    Hydroxylated surfactant micelles are powerful catalysts for the deacylation of N-acylimidazoles under neutral conditions; the deacylation rates of hydrophobia acylimidazoles are accelerated remarkably by functionalized micelles containing three hydroxy groups at the polar head.

  2. Cell signalling and phospholipid metabolism. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Boss, W.F.

    1990-12-31

    These studies explored whether phosphoinositide (PI) has a role in plants analogous to its role in animal cells. Although no parallel activity of PI in signal transduction was found in plant cells, activity of inositol phospholipid kinase was found to be modulated by light and by cell wall degrading enzymes. These studies indicate a major role for inositol phospholipids in plant growth and development as membrane effectors but not as a source of second messengers.

  3. Mechanism of Molecular Exchange in Copolymer Micelles

    Science.gov (United States)

    Choi, Soo-Hyung; Lodge, Timothy; Bates, Frank

    2010-03-01

    Compared to thermodynamic structure, much less has been known about the kinetics of block copolymer micelles which should underlay the attainment of thermodynamic equilibrium. In this presentation, molecular exchange between spherical micelles formed by isotopically labeled diblock copolymers was investigated using time-resolved small-angle neutron scattering. Two pairs of structurally matched poly(styrene-b-ethylene-alt-propylene) (PS-PEP) were synthesized and dispersed in isotopic mixture of squalane, highly selective to PEP block. Each pair includes polymers with fully deuterated (dPS-PEP) and a normal (hPS-PEP) PS blocks. Temperature dependence of the micelle exchange rate R(t) is consistent with melt dynamics for the core polymer. Furthermore, R(t) is significantly sensitive to the core block length N due to the thermodynamic penalty associated with ejecting a core block into the solvent. This hypersensitivity, combined with modest polydispersity in N, leads to an approximately logarithmic decay in R(t).

  4. Statistical crystallography of surface micelle spacing

    Science.gov (United States)

    Noever, David A.

    1992-01-01

    The aggregation of the recently reported surface micelles of block polyelectrolytes is analyzed using techniques of statistical crystallography. A polygonal lattice (Voronoi mosaic) connects center-to-center points, yielding statistical agreement with crystallographic predictions; Aboav-Weaire's law and Lewis's law are verified. This protocol supplements the standard analysis of surface micelles leading to aggregation number determination and, when compared to numerical simulations, allows further insight into the random partitioning of surface films. In particular, agreement with Lewis's law has been linked to the geometric packing requirements of filling two-dimensional space which compete with (or balance) physical forces such as interfacial tension, electrostatic repulsion, and van der Waals attraction.

  5. Polymeric micelles as carriers of diagnostic agents.

    Science.gov (United States)

    Trubetskoy

    1999-04-01

    This review deals with diagnostic applications of polymeric micelles composed of amphiphilic block-copolymers. In aqueous solutions these polymers spontaneously form particles with diameter 20-100 nm. A variety of diagnostic moieties can be incorporated covalently or non-covalently into the particulates with high loads. Resulting particles can be used as particulate agents for diagnostic imaging using three major imaging modalities: gamma-scintigraphy, magnetic resonance imaging and computed tomography. The use of polyethyleneoxide-diacyllipid micelles loaded with chelated (111)In/Gd(3+) as well as iodine-containing amphiphilic copolymer in percutaneous lymphography and blood pool/liver imaging are discussed as specific examples.

  6. Self-assembling micelle-like nanoparticles with detachable envelopes for enhanced delivery of nucleic acid therapeutics.

    Science.gov (United States)

    Battogtokh, Gantumur; Ko, Young Tag

    2014-03-01

    In spite of the great potential of nucleic acids as therapeutic agents, the clinical application of nucleic acid therapeutics requires the development of effective systemic delivery strategies. In an effort to develop effective nucleic acid delivery systems suitable for clinical application, we previously reported a self-assembling micelle-like nanoparticle that was based on phospholipid-polyethylenimine conjugates, i.e., "micelle-like nanoparticles" (MNPs). In this study, we aimed to improve the system by enhancing the efficiency of intracellular delivery of the payload via pH-responsive detachment of the monolayer envelope and release of the nucleic acid therapeutics upon reaching the target tissues with an acidic pH, e.g., tumors. The acid-cleavable phospholipid-polyethylenimine conjugate was synthesized via hydrazone bond, and acid-cleavable MNPs were then prepared and characterized as before. We evaluated the acid-cleavable MNP construct for in vitro and in vivo nucleic acid delivery efficiency using cultured tumor cells and tumor-bearing mice. The acid-cleavable nanocarrier showed an enhanced cellular delivery at pH 6.5 as compared to pH 7.4, whereas the noncleavable nanocarrier did not show any differences. Tail vein injections also led to enhanced intracellular uptake of the acid-cleavable nanocarrier compared to the noncleavable nanocarrier into tumor cells of tumor-bearing mice although no significant difference was observed in total tumor accumulation.

  7. POLYMER MICELLE INTERACTIONS - PHYSICAL ORGANIC ASPECTS

    NARCIS (Netherlands)

    BRACKMAN, JC; ENGBERTS, JBFN

    1993-01-01

    This review presents a summary of attempts to characterize the morphology of the complexes formed between ionic and non-ionic surfactants and water-soluble polymers. It is now generally accepted that complex formation involves the binding of micelles to the macromolecule. This binding process modifi

  8. Molecular Exchange Dynamics in Block Copolymer Micelles

    Science.gov (United States)

    Bates, Frank; Lu, Jie; Choi, Soohyung; Lodge, Timothy

    2012-02-01

    Poly(styrene-b-ethylene propylene) (PS-PEP) diblock copolymers were mixed with squalane (C30H62) at 1% by weight resulting in the formation of spherical micelles. The structure and dynamics of molecular exchange were characterized by synchrotron small-angle x-ray scattering (SAXS) and time resolved small-angle neutron scattering (TR-SANS), respectively, between 100 C and 160 C. TR-SANS measurements were performed with solutions initially containing deuterium labeled micelle cores and normal cores dispersed in a contrast matched squalane. Monitoring the reduction in scattering intensity as a function of time at various temperatures revealed molecular exchange dynamics highly sensitive to the core molecular weight and molecular weight distribution. Time-temperature superposition of data acquired at different temperatures produced a single master curve for all the mixtures. Experiments conducted with isotopically labeled micelle cores, each formed from two different but relatively mondisperse PS blocks, confirmed a simple dynamical model based on first order kinetics and core Rouse single chain relaxation. These findings demonstrate a dramatic transition to nonergodicity with increasing micelle core molecular weight and confirm the origins of the logarithmic exchange kinetics in such systems.

  9. Chain exchange in block copolymer micelles

    Science.gov (United States)

    Lu, Jie; Bates, Frank; Lodge, Timothy

    2014-03-01

    Block copolymer micelles are aggregates formed by self-assembly of amphiphilic copolymers dispersed in a selective solvent, driven by unfavorable interactions between the solvent and the core-forming block. Due to the relatively long chains being subject to additional thermodynamic and dynamic constraints (e.g., entanglements, crystallinity, vitrification), block copolymer micelles exhibit significantly slower equilibration kinetics than small molecule surfactants. As a result, details of the mechanism(s) of equilibration in block copolymer micelles remain unclear. This present works focuses on the chain exchange kinetics of poly(styrene-b-ethylenepropylene) block copolymers in squalane (C30H62) using time-resolved small angle neutron scattering (TR-SANS). A mixture of h-squalane and d-squalane is chosen so that it contrast matches a mixed 50/50 h/d polystyrene micelle core. When the temperature is appropriate and isotopically labeled chains undergo mixing, the mean core contrast with respect to the solvent decreases, and the scattering intensity is therefore reduced. This strategy allows direct probing of chain exchange rate from the time dependent scattering intensity I(q, t).

  10. A facile surfactant critical micelle concentration determination

    OpenAIRE

    Cai, Lifeng; Gochin, Miriam; Liu, Keliang

    2011-01-01

    Liquid surface curvature variations in microplate wells due to different liquid surface tension cause significant signal change in spectroscopic measurement using a plate reader with a vertical detecting light beam. The signals have been quantitated and used to develop a method for facile surfactant critical micelle concentration determination.

  11. Spontaneous symmetry breaking: formation of Janus micelles

    NARCIS (Netherlands)

    Voets, I.K.; Fokkink, R.G.; Hellweg, T.; King, S.M.; Waard, de P.; Keizer, de A.; Cohen Stuart, M.A.

    2009-01-01

    We describe the preparation and solution properties of Janus micelles, i.e., non-centrosymmetric nanoparticles with compartmentalized shells, via co-assembly of two fully water-soluble block copolymers. They consist of a mixed core of poly(N-methyl-2-vinyl pyridinium iodide) (P2MVP) and poly(acrylic

  12. Pros and cons of phospholipid asymmetry in erythrocytes

    Directory of Open Access Journals (Sweden)

    Aiswarya Sathi

    2014-01-01

    Full Text Available Phospholipids of erythrocyte are found as bilayer with choline containing phospholipid like phosphatidyl choline and sphingomylein in the outer layer and amine containing phospholipid like phosphatidyl ethanolamine and phosphatidyl serine in the inner layer. This arrangement is known as phospholipid asymmetry. Lipid asymmetry is maintained throughout the entire life span of red blood cell and is disturbed when cells enter into the stage of apoptosis. We here discuss some of the conditions in which phospholipid asymmetry of erythrocyte is maintained and disturbed and the various detection methods to check the distortion phospholipid asymmetry of it.

  13. Packing of ganglioside-phospholipid monolayers

    DEFF Research Database (Denmark)

    Majewski, J.; Kuhl, T.L.; Kjær, K.;

    2001-01-01

    Using synchrotron grazing-incidence x-ray diffraction (GIXD) and reflectivity, the in-plane and out-of-plane structure of mixed ganglioside-phospholipid monolayers was investigated at the air-water interface. Mixed monolayers of 0, 5, 10, 20, and 100 mol% ganglioside GM, and the phospholipid dipa...... polymer groups. Indeed, the lack of packing disruptions by the oligosaccharide groups indicates that protein-GM, interactions, including binding, insertion, chain fluidization, and domain formation (lipid rafts), can be studied in 2-D monolayers using scattering techniques....... monolayers did not affect hydrocarbon tail packing (fluidization or condensation of the hydrocarbon region). This is in contrast to previous investigations of lipopolymer-lipid mixtures, where the packing structure of phospholipid monolayers was greatly altered by the inclusion of lipids bearing hydrophilic...

  14. Hybrid, Nanoscale Phospholipid/Block Copolymer Vesicles

    Directory of Open Access Journals (Sweden)

    Bo Liedberg

    2013-09-01

    Full Text Available Hybrid phospholipid/block copolymer vesicles, in which the polymeric membrane is blended with phospholipids, display interesting self-assembly behavior, incorporating the robustness and chemical versatility of polymersomes with the softness and biocompatibility of liposomes. Such structures can be conveniently characterized by preparing giant unilamellar vesicles (GUVs via electroformation. Here, we are interested in exploring the self-assembly and properties of the analogous nanoscale hybrid vesicles (ca. 100 nm in diameter of the same composition prepared by film-hydration and extrusion. We show that the self-assembly and content-release behavior of nanoscale polybutadiene-b-poly(ethylene oxide (PB-PEO/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC hybrid phospholipid/block copolymer vesicles can be tuned by the mixing ratio of the amphiphiles. In brief, these hybrids may provide alternative tools for drug delivery purposes and molecular imaging/sensing applications and clearly open up new avenues for further investigation.

  15. Preparation and Evaluation of Inhalable Itraconazole Chitosan Based Polymeric Micelles

    Directory of Open Access Journals (Sweden)

    Esmaeil Moazeni

    2012-12-01

    Full Text Available Background: This study evaluated the potential of chitosan based polymeric micelles as a nanocarrier system for pulmonary delivery of itraconazole (ITRA.Methods: Hydrophobically modified chitosan were synthesized by conjugation of stearic acid to the hydrophilic depolymerized chitosan. FTIR and 1HNMR were used to prove the chemical structure and physical properties of the depolymerized and the stearic acid grafted chitosan. ITRA was entrapped into the micelles and physicochemical properties of the micelles were investigated. Fluorescence spectroscopy, dynamic laser light scattering andtransmission electron microscopy were used to characterize the physicochemical properties of the prepared micelles. The in vitro pulmonary profile of polymeric micelles was studied by an air-jet nebulizer connected to a twin stage impinger.Results: The polymeric micelles prepared in this study could entrap up to 43.2±2.27 μg of ITRA per milliliter. All micelles showed mean diameter between 120–200 nm. The critical micelle concentration of the stearic acid grafted chitosan was found to be 1.58×10-2 mg/ml. The nebulization efficiency was up to 89% and the fine particle fraction (FPF varied from 38% to 47%. The micelles had enough stability to remain encapsulation of the drug during nebulization process.Conclusions: In vitro data showed that stearic acid grafted chitosan based polymeric micelles has a potential to be used as nanocarriers for delivery of itraconazole through inhalation.

  16. Structural changes in block copolymer micelles induced by cosolvent mixtures

    Energy Technology Data Exchange (ETDEWEB)

    Kelley, Elizabeth G.; Smart, Thomas P.; Jackson, Andrew J.; Sullivan, Millicent O.; Epps, III, Thomas H. (Delaware)

    2012-11-26

    We investigated the influence of tetrahydrofuran (THF) addition on the structure of poly(1,2-butadiene-b-ethylene oxide) [PB-PEO] micelles in aqueous solution. Our studies showed that while the micelles remained starlike, the micelle core-corona interfacial tension and micelle size decreased upon THF addition. The detailed effects of the reduction in interfacial tension were probed using contrast variations in small angle neutron scattering (SANS) experiments. At low THF contents (high interfacial tensions), the SANS data were fit to a micelle form factor that incorporated a radial density distribution of corona chains to account for the starlike micelle profile. However, at higher THF contents (low interfacial tensions), the presence of free chains in solution affected the scattering at high q and required the implementation of a linear combination of micelle and Gaussian coil form factors. These SANS data fits indicated that the reduction in interfacial tension led to broadening of the core-corona interface, which increased the PB chain solvent accessibility at intermediate THF solvent fractions. We also noted that the micelle cores swelled with increasing THF addition, suggesting that previous assumptions of the micelle core solvent content in cosolvent mixtures may not be accurate. Control over the size, corona thickness, and extent of solvent accessible PB in these micelles can be a powerful tool in the development of targeting delivery vehicles.

  17. Interaction of lactoferrin and lysozyme with casein micelles.

    Science.gov (United States)

    Anema, Skelte G; de Kruif, C G Kees

    2011-11-14

    On addition of lactoferrin (LF) to skim milk, the turbidity decreases. The basic protein binds to the caseins in the casein micelles, which is then followed by a (partial) disintegration of the casein micelles. The amount of LF initially binding to casein micelles follows a Langmuir adsorption isotherm. The kinetics of the binding of LF could be described by first-order kinetics and similarly the disintegration kinetics. The disintegration was, however, about 10 times slower than the initial adsorption, which allowed investigating both phenomena. Kinetic data were also obtained from turbidity measurements, and all data could be described with one equation. The disintegration of the casein micelles was further characterized by an activation energy of 52 kJ/mol. The initial increase in hydrodynamic size of the casein micelles could be accounted for by assuming that it would go as the cube root of the mass using the adsorption and disintegration kinetics as determined from gel electrophoresis. The results show that LF binds to casein micelles and that subsequently the casein micelles partly disintegrate. All micelles behave in a similar manner as average particle size decreases. Lysozyme also bound to the casein micelles, and this binding followed a Langmuir adsorption isotherm. However, lysozyme did not cause the disintegration of the casein micelles. PMID:21932853

  18. Enzymatic modification of phospholipids forfunctional applications and human nutrition

    DEFF Research Database (Denmark)

    Guo, Zheng; Vikbjerg, Anders / Falk; Xu, Xuebing

    2005-01-01

    Rapid progress in biochemistry of phospholipids and evolution of modern bioengineering has brought forth a number of novel concepts and technical advancements in the modification of phospholipids for industrial applications and human nutrition. Highlights cover preparation of novel phospholipid...... analogs based on the latest understanding of pivotal role of phospholipids in manifold biological processes, exploration of remarkable application potentials of phospholipids in meliorating human health, as well as development of new chemical and biotechnological approaches applied to the modification...... of phospholipids. This work reviews the natural occurrence and structural characteristics of phospholipids, their updated knowledge on manifold biological and nutritional functions, traditional and novel physical and chemical approaches to modify phospholipids as well as their applications to obtain novel...

  19. Tryptophan probes reveal residue-specific phospholipid interactions of apolipoprotein C-III.

    Science.gov (United States)

    Pfefferkorn, Candace M; Walker, Robert L; He, Yi; Gruschus, James M; Lee, Jennifer C

    2015-11-01

    Apolipoproteins are essential human proteins for lipid metabolism. Together with phospholipids, they constitute lipoproteins, nm to μm sized particles responsible for transporting cholesterol and triglycerides throughout the body. To investigate specific protein-lipid interactions, we produced and characterized three single-Trp containing apolipoprotein C-III (ApoCIII) variants (W42 (W54F/W65F), W54 (W42F/W65F), W65 (W42F/W54F)). Upon binding to phospholipid vesicles, wild-type ApoCIII adopts an α-helical conformation (50% helicity) as determined by circular dichroism spectroscopy with an approximate apparent partition constant of 3×10(4) M(-1). Steady-state and time-resolved fluorescence measurements reveal distinct residue-specific behaviors with W54 experiencing the most hydrophobic environment followed by W42 and W65. Interestingly, time-resolved anisotropy measurements show a converse trend for relative Trp mobility with position 54 being the least immobile. To determine the relative insertion depths of W42, W54, and W65 in the bilayer, fluorescence quenching experiments were performed using three different brominated lipids. W65 had a clear preference for residing near the headgroup while W54 and W42 sample the range of depths ~8-11 Å from the bilayer center. On average, W54 is slightly more embedded than W42. Based on Trp spectral differences between ApoCIII binding to phospholipid vesicles and sodium dodecyl sulfate micelles, we suggest that ApoCIII adopts an alternate helical conformation on the bilayer which could have functional implications.

  20. On the stability and morphology of complex coacervate core micelles: from spherical to wormlike micelles.

    Science.gov (United States)

    van der Kooij, Hanne M; Spruijt, Evan; Voets, Ilja K; Fokkink, Remco; Cohen Stuart, Martien A; van der Gucht, Jasper

    2012-10-01

    We present a systematic study of the stability and morphology of complex coacervate core micelles (C3Ms) formed from poly(acrylic acid) (PAA) and poly(N-methyl-2-vinylpyridinium)-b-poly(ethylene oxide) (PM2VP-b-PEO). We use polarized and depolarized dynamic and static light scattering, combined with small-angle X-ray scattering, to investigate how the polymer chain length and salt concentration affect the stability, size, and shape of these micelles. We show that C3Ms are formed in aqueous solution below a critical salt concentration, which increases considerably with increasing PAA and PM2VP length and levels off for long chains. This trend is in good agreement with a mean-field model of polyelectrolyte complexation based on the Voorn-Overbeek theory. In addition, we find that salt induces morphological changes in C3Ms when the PAA homopolymer is sufficiently short: from spherical micelles with a diameter of several tens of nanometers at low salt concentration to wormlike micelles with a contour length of several hundreds of nanometers just before the critical salt concentration. By contrast, C3Ms of long PAA homopolymers remain spherical upon addition of salt and shrink slightly. A critical review of existing literature on other C3Ms reveals that the transition from spherical to wormlike micelles is probably a general phenomenon, which can be rationalized in terms of a classical packing parameter for amphiphiles.

  1. Storage stability of marine phospholipids emulsions

    DEFF Research Database (Denmark)

    Lu, Henna Fung Sieng; Nielsen, Nina Skall; Baron, Caroline Pascale;

    Marine phospholipids (MPL) are believed to provide more advantages than fish oil from the same source. They are considered to have a better bioavailability, a better resistance towards oxidation and a higher content of polyunsaturated fatty acids such as eicosapentaenoic (EPA) and docosahexaenoic...

  2. Spectrin-phospholipid interaction. A monolayer study

    NARCIS (Netherlands)

    Mombers, C.; Gier, J. de; Demel, R.A.; Deenen, L.L.M. van

    1980-01-01

    1.(1) The interaction of synthetic and natural phospholipids with spectrin, purified from human erythrocyte membranes, was studied using the monolayer technique at constant surface pressure. Spectrin penetration into the lipid monolayer was recorded as the rate of surface area increase on a two-comp

  3. The Lantibiotic Nisin Induces Transmembrane Movement of a Fluorescent Phospholipid

    NARCIS (Netherlands)

    Moll, Gert N.; Konings, Wil N.; Driessen, Arnold J.M.

    1998-01-01

    Nisin is a pore-forming antimicrobial peptide. The capacity of nisin to induce transmembrane movement of a fluorescent phospholipid in lipid vesicles was investigated. Unilamellar phospholipid vesicles that contained a fluorescent phospholipid (1-acyl-2-{6-[(7-nitro-2-1,3-benzoxadiazol-4-yl)amino]ca

  4. Implicit solvent simulations of DPC micelle formation.

    Science.gov (United States)

    Lazaridis, Themis; Mallik, Buddhadeb; Chen, Yong

    2005-08-11

    The formation of micelles by dodecylphosphocholine (DPC) is modeled by treating the surfactants in atomic detail and the solvent implicitly, in the spirit of the EEF1 solvation model for proteins. The solvation parameters of the DPC atoms are carried over from those of similar atoms in proteins. A slight adjustment of the parameters for the headgroup was found necessary for obtaining an aggregation number consistent with experiment. Molecular dynamics simulations of 960 DPC molecules at different concentrations are used to obtain the aggregation number, the micelle size distribution, and the CMC. At 20 mM concentration we obtain an aggregation number of 53-56 and a CMC of 1.25 mM, values close to the experimental ones. At 100 mM the aggregation number increases to 90. Simulations of individual micelles of varying size show that the effective energy per surfactant molecule is initially a decreasing function of aggregation number but stabilizes at about 60 molecules. The van der Waals term and the desolvation of nonpolar groups contribute to micellization, whereas the desolvation of polar groups opposes it. From the difference between the effective energy and the free energy (calculated from the CMC), the translational and rotational entropy contributions to the free energy are estimated at about 7 kcal/mol per monomer. The micelles obtained here are more irregular than those obtained in explicit water simulations. This modeling approach allows the study of larger surfactant aggregates for longer times and the extraction of thermodynamic in addition to structural information. PMID:16852911

  5. Chain exchange in triblock copolymer micelles

    Science.gov (United States)

    Lu, Jie; Lodge, Timothy; Bates, Frank

    2015-03-01

    Block polymer micelles offer a host of technological applications including drug delivery, viscosity modification, toughening of plastics, and colloidal stabilization. Molecular exchange between micelles directly influences the stability, structure and access to an equilibrium state in such systems and this property recently has been shown to be extraordinarily sensitive to the core block molecular weight in diblock copolymers. The dependence of micelle chain exchange dynamics on molecular architecture has not been reported. The present work conclusively addresses this issue using time-resolved small-angle neutron scattering (TR-SANS) applied to complimentary S-EP-S and EP-S-EP triblock copolymers dissolved in squalane, a selective solvent for the EP blocks, where S and EP refer to poly(styrene) and poly(ethylenepropylene), respectively. Following the overall SANS intensity as a function of time from judiciously deuterium labelled polymer and solvent mixtures directly probes the rate of molecular exchange. Remarkably, the two triblocks display exchange rates that differ by approximately ten orders of magnitude, even though the solvophobic S blocks are of comparable size. This discovery is considered in the context of a model that successfully explains S-EP diblock exchange dynamics.

  6. Toward a Standard Protocol for Micelle Simulation.

    Science.gov (United States)

    Johnston, Michael A; Swope, William C; Jordan, Kirk E; Warren, Patrick B; Noro, Massimo G; Bray, David J; Anderson, Richard L

    2016-07-01

    In this paper, we present protocols for simulating micelles using dissipative particle dynamics (and in principle molecular dynamics) that we expect to be appropriate for computing micelle properties for a wide range of surfactant molecules. The protocols address challenges in equilibrating and sampling, specifically when kinetics can be very different with changes in surfactant concentration, and with minor changes in molecular size and structure, even using the same force field parameters. We demonstrate that detection of equilibrium can be automated and is robust, for the molecules in this study and others we have considered. In order to quantify the degree of sampling obtained during simulations, metrics to assess the degree of molecular exchange among micellar material are presented, and the use of correlation times are prescribed to assess sampling and for statistical uncertainty estimates on the relevant simulation observables. We show that the computational challenges facing the measurement of the critical micelle concentration (CMC) are somewhat different for high and low CMC materials. While a specific choice is not recommended here, we demonstrate that various methods give values that are consistent in terms of trends, even if not numerically equivalent. PMID:27096611

  7. Modulating alignment of membrane proteins in liquid-crystalline and oriented gel media by changing the size and charge of phospholipid bicelles

    Energy Technology Data Exchange (ETDEWEB)

    Lorieau, Justin L.; Maltsev, Alexander S.; Louis, John M.; Bax, Ad, E-mail: bax@nih.gov [National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health, Laboratory of Chemical Physics (United States)

    2013-04-15

    We demonstrate that alignment of a structured peptide or small protein solubilized in mixed phospholipid:detergent micelles or bicelles, when embedded in a compressed gel or liquid crystalline medium, can be altered by either changing the phospholipid aggregate shape, charge, or both together. For the hemagglutinin fusion peptide solubilized in bicelles, we show that bicelle shape and charge do not change its helical hairpin structure but impact its alignment relative to the alignment medium, both in charged compressed acrylamide gel and in liquid crystalline d(GpG). The method can be used to generate sets of residual dipolar couplings that correspond to orthogonal alignment tensors, and holds promise for high-resolution structural refinement and dynamic mapping of membrane proteins.

  8. Diclofenac/biodegradable polymer micelles for ocular applications

    Science.gov (United States)

    Li, Xingyi; Zhang, Zhaoliang; Li, Jie; Sun, Shumao; Weng, Yuhua; Chen, Hao

    2012-07-01

    In this paper, methoxypoly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) micelle formulations as promising nano-carriers for poorly water soluble drugs were investigated for the delivery of diclofenac to the eye. Diclofenac loaded MPEG-PCL micelles were prepared by a simple solvent-diffusion method and characterized by dynamic light scattering (DLS), atomic force microscopy (AFM), Fourier transform infra-red (FTIR), X-ray diffraction (XRD), differential scanning calorimetery (DSC), etc. With the analysis of XRD and DSC, the diclofenac was present as an amorphous state in the formulation. The in vitro release profile indicated a sustained release manner of diclofenac from the micelles. Meanwhile, in vivo studies on eye irritation were performed with blank MPEG-PCL micelles (200 mg ml-1). The results showed that the developed MPEG-PCL micelles were non-irritants to the eyes of rabbits. In vitro penetration studies across the rabbit cornea demonstrated that the micelle formulations exhibited a 17-fold increase in penetration compared with that of diclofenac phosphate buffered saline (PBS) solution. The in vivo pharmacokinetics profile of the micelle parent drug in the aqueous humor of the rabbit was evaluated and the data showed that the diclofenac loaded MPEG-PCL micelles exhibited a 2-fold increase in AUC0-24 h than that of the diclofenac PBS solution eye drops. These results suggest a great potential of our micelle formulations as a novel ocular drug delivery system to improve the bioavailability of the drugs.

  9. The critical micelle concentration of tetraethylammonium perfluorooctylsulfonate in water.

    Science.gov (United States)

    López-Fontán, José L; González-Pérez, Alfredo; Costa, Julian; Ruso, Juan M; Prieto, Gerardo; Schulz, Pablo C; Sarmiento, Félix

    2006-02-15

    The aggregation characteristics of tetraethylammonium perfluorooctylsulfonate in water were studied by several techniques: conductivity, pH, ion-selective electrodes, and surface tension. It was concluded that the aggregation process is gradual and starts with the formation of oligomers such as ion pairs that grow to give spherical micelles, which become wormlike with increasing concentration. Because of the size and hydrophobicity of the counterion, micelles quickly increase in ionization degree up to about 0.5. Differences among different critical micelle concentration values in the literature are explained on the basis of the gradual formation of micelles.

  10. Photophysical properties of pyronin dyes in reverse micelles of AOT

    Energy Technology Data Exchange (ETDEWEB)

    Bayraktutan, Tuğba; Meral, Kadem; Onganer, Yavuz, E-mail: yonganer@atauni.edu.tr

    2014-01-15

    The photophysical properties of pyronin B (PyB) and pyronin Y (PyY) in reverse micelles formed with water/sodium bis (2-ethyl-1-hexyl) sulfosuccinate (AOT)/n-heptane were investigated by UV–vis absorption, steady-state and time-resolved fluorescence spectroscopy techniques. This study was carried out a wide range of reverse micelle sizes, with hydrodynamic radii ranging from 1.85 to 9.38 nm. Significant photophysical parameters as band shifts, fluorescence quantum yields and fluorescence lifetimes were determined to understand how photophysical and spectroscopic features of the dye compounds were affected by the variation of reverse micelle sizes. In this regard, control of reverse micelle size by changing W{sub 0}, the molar ratio of water to surfactant, allowed tuning the photophysical properties of the dyes in organic solvent via reverse micelle. Non-fluorescent H-aggregates of pyronin dyes were observed for the smaller reverse micelles whereas an increase in the reverse micelle size induced an increment in the amount of dye monomers instead of dye aggregates. Thus, the fluorescence intensities of the dyes were improved by increasing W{sub 0} due to the predomination of the fluorescent dye monomers. As a result, the fluorescence quantum yields also increased. The fluorescence lifetimes of the dyes in the reverse micelles were determined by the time-resolved fluorescence decay studies. Evaluation of the fluorescence lifetimes calculated for pyronin dyes in the reverse micelles showed that the size of reverse micelle affected the fluorescence lifetimes of pyronin dyes. -- Highlights: • The photophysical properties of pyronin dyes were examined by spectroscopic techniques. • Optical properties of the dyes were tuned by changing of W{sub 0} values. • The fluorescence lifetime and quantum yield values of the dyes in reverse micelles were discussed.

  11. Interaction of isopropylthioxanthone with phospholipid liposomes.

    Science.gov (United States)

    Momo, Federico; Fabris, Sabrina; Stevanato, Roberto

    2007-04-01

    Isopropylthioxanthone (ITX) is a highly lipophilic molecule which can be released in foods and beverages from the packages, where it is present as photoinitiator of inks in printing processes. Recently it was found in babies milk, and its toxicity cannot be excluded. The structure of the molecule suggests a possible strong interaction with the lipid moiety of biological membranes, and this is the first study of its effects on phospholipid organization, using differential scanning calorimetry (DSC) and spin labelling techniques. The data obtained with multilamellar liposomes of saturated phospholipids of different length, with and without cholesterol, point out that the molecule changes the lipid structure; in particular, in the gel state, behaving like a disordering agent it increases the mobility of the bilayer, while, in the fluid state, tends to rigidify the membrane, in a cholesterol like way. This behavior supports the hypothesis that ITX experiences a relocation process when the lipid matrix passes from the gel to the fluid state.

  12. Dietary Phospholipids and Intestinal Cholesterol Absorption

    OpenAIRE

    Sally Tandy; Chung, Rosanna W. S.; Elaine Wat; Alvin Kamili; Cohn, Jeffrey S.

    2010-01-01

    Experiments carried out with cultured cells and in experimental animals have consistently shown that phospholipids (PLs) can inhibit intestinal cholesterol absorption. Limited evidence from clinical studies suggests that dietary PL supplementation has a similar effect in man. A number of biological mechanisms have been proposed in order to explain how PL in the gut lumen is able to affect cholesterol uptake by the gut mucosa. Further research is however required to establish whether the abili...

  13. Conducting gramicidin channel activity in phospholipid monolayers.

    OpenAIRE

    A. Nelson

    2001-01-01

    Potential step amperometry (chronoamperometry) of the Tl(I)/Tl(Hg) electrochemical reduction process has been used to investigate the underlying mechanisms of gramicidin activity in phospholipid monolayers. The experiments were carried out at gramicidin-modified dioleoyl phosphatidylcholine (DOPC)-coated electrodes. Application of a potential step to the coated electrode system results in a current transient that can be divided into two regions. An initial exponential decay of current corresp...

  14. Annexin-Phospholipid Interactions. Functional Implications

    Directory of Open Access Journals (Sweden)

    Javier Turnay

    2013-01-01

    Full Text Available Annexins constitute an evolutionary conserved multigene protein superfamily characterized by their ability to interact with biological membranes in a calcium dependent manner. They are expressed by all living organisms with the exception of certain unicellular organisms. The vertebrate annexin core is composed of four (eight in annexin A6 homologous domains of around 70 amino acids, with the overall shape of a slightly bent ring surrounding a central hydrophilic pore. Calcium- and phospholipid-binding sites are located on the convex side while the N-terminus links domains I and IV on the concave side. The N-terminus region shows great variability in length and amino acid sequence and it greatly influences protein stability and specific functions of annexins. These proteins interact mainly with acidic phospholipids, such as phosphatidylserine, but differences are found regarding their affinity for lipids and calcium requirements for the interaction. Annexins are involved in a wide range of intra- and extracellular biological processes in vitro, most of them directly related with the conserved ability to bind to phospholipid bilayers: membrane trafficking, membrane-cytoskeleton anchorage, ion channel activity and regulation, as well as antiinflammatory and anticoagulant activities. However, the in vivo physiological functions of annexins are just beginning to be established.

  15. Separation of amino acid enantiomers by micelle-enhanced ultrafiltration

    NARCIS (Netherlands)

    Bruin, de T.J.M.; Marcelis, A.T.M.; Zuilhof, H.; Rodenburg, L.M.; Overdevest, P.E.M.; Padt, van der A.; Sudhölter, E.J.R.

    2000-01-01

    A Micelle-enhanced ultrafiltration (MEUF) separation process was investigated that can potentially be used for large-scale enantioseparations. Copper(II)-amino acid derivatives dissolved in nonionic surfactant micelles were used as chiral selectors for the separation of dilute racemic amino acids so

  16. Structure and stability of complex coacervate core micelles with lysozyme

    NARCIS (Netherlands)

    Lindhoud, Saskia; de Vries, Renko; Norde, Willem; Cohen Stuart, Martien A.

    2007-01-01

    Encapsulation of enzymes by polymers is a promising method to influence their activity and stability. Here, we explore the use of complex coacervate core micelles for encapsulation of enzymes. The core of the micelles consists of negatively charged blocks of the diblock copolymer PAA(42)PAAm(417) an

  17. Structure and Stability of Complex Coacervate Core Micelles with Lysozyme

    NARCIS (Netherlands)

    Lindhoud, Saskia; Vries, de Renko; Norde, Willem; Cohen Stuart, Martien A.

    2007-01-01

    Encapsulation of enzymes by polymers is a promising method to influence their activity and stability. Here, we explore the use of complex coacervate core micelles for encapsulation of enzymes. The core of the micelles consists of negatively charged blocks of the diblock copolymer PAA42PAAm417 and th

  18. Structure and stability of complex coacervate core micelles with lysozyme

    NARCIS (Netherlands)

    Lindhoud, S.; Vries, de R.J.; Norde, W.; Cohen Stuart, M.A.

    2007-01-01

    Encapsulation of enzymes by polymers is a promising method to influence their activity and stability. Here, we explore the use of complex coacervate core micelles for encapsulation of enzymes. The core of the micelles consists of negatively charged blocks of the diblock copolymer PAA42PAAm417 and th

  19. Stimuli-responsive biodegradable polymeric micelles for targeted cancer therapy

    NARCIS (Netherlands)

    Talelli, M.A.

    2011-01-01

    Thermosensitive and biodegradable polymeric micelles based on mPEG-b-pHPMAmLacn have shown very promising results during the past years. The results presented in this thesis illustrate the high potential of these micelles for anticancer therapy and imaging and fully justify further pharmaceutical de

  20. Absorption Complex between Porphyrin and Phenothiazine in Reverse Micelles

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The interaction between amphiphilic porphyrin and phenothiazine in AOT/isooctane/ water reverse micelle was investigated by UV-Vis spectra. A new absorption complex between the two species is formed in such circumstances, which is ascribed to the enrichment of the components by the reverse micelle. The fluorescence quenching of CHTTP by PTH becomes more efficient after the formation of the absorption complex.

  1. DEFORMATION OF COPOLYMER MICELLES INDUCED BY AMPHIPHILIC DIMER PARTICLES

    Institute of Scientific and Technical Information of China (English)

    Xiao-chun Qin; Chun-lai Ren

    2012-01-01

    Combining self-consistent-field theory and density-functional theory,we systematically study the deformation of copolymer micelles induced by the presence of amphiphilic dimer particles.Due to the amphiphilic nature,dimer particles tend to accumulate onto the interface of the copolymer micelle.With increasing concentration of the symmetric dimer particles,which are made of two identical spherical particles,the micelle deforms from the initial sphere to ellipse,dumbbell,and finally separates into two micelles.Furthermore,asymmetric dimer particles,composed by two particles with different sizes,are considered to investigate the influence of geometry of dimer particles on the deformation of the micelle.It is found that the micelle inclines to deform into dumbbell due to the additional curvature originating in the gathering of asymmetric dimer particles onto the interface of the micelle.The present study on the deformation of micelles is useful to understand the possible shape variation in the course of cell division/fusion.

  2. Use of reverse micelles in membrane protein structural biology

    Energy Technology Data Exchange (ETDEWEB)

    Van Horn, Wade D. [Vanderbilt University School of Medicine, Department of Biochemistry and Center for Structural Biology (United States); Ogilvie, Mark E.; Flynn, Peter F. [University of Utah, Department of Chemistry (United States)], E-mail: peter.flynn@utah.edu

    2008-03-15

    Membrane protein structural biology is a rapidly developing field with fundamental importance for elucidating key biological and biophysical processes including signal transduction, intercellular communication, and cellular transport. In addition to the intrinsic interest in this area of research, structural studies of membrane proteins have direct significance on the development of therapeutics that impact human health in diverse and important ways. In this article we demonstrate the potential of investigating the structure of membrane proteins using the reverse micelle forming surfactant dioctyl sulfosuccinate (AOT) in application to the prototypical model ion channel gramicidin A. Reverse micelles are surfactant based nanoparticles which have been employed to investigate fundamental physical properties of biomolecules. The results of this solution NMR based study indicate that the AOT reverse micelle system is capable of refolding and stabilizing relatively high concentrations of the native conformation of gramicidin A. Importantly, pulsed-field-gradient NMR diffusion and NOESY experiments reveal stable gramicidin A homodimer interactions that bridge reverse micelle particles. The spectroscopic benefit of reverse micelle-membrane protein solubilization is also explored, and significant enhancement over commonly used micelle based mimetic systems is demonstrated. These results establish the effectiveness of reverse micelle based studies of membrane proteins, and illustrate that membrane proteins solubilized by reverse micelles are compatible with high resolution solution NMR techniques.

  3. Magainin II modified polydiacetylene micelles for cancer therapy

    Science.gov (United States)

    Yang, Danling; Zou, Rongfeng; Zhu, Yu; Liu, Ben; Yao, Defan; Jiang, Juanjuan; Wu, Junchen; Tian, He

    2014-11-01

    Polydiacetylene (PDA) micelles have been widely used to deliver anticancer drugs in the treatment of a variety of tumours and for imaging living cells. In this study, we developed an effective strategy to directly conjugate magainin II (MGN-II) to the surface of PDA micelles using a fluorescent dye. These stable and well-defined PDA micelles had high cytotoxicity in cancer cell lines, and were able to reduce the tumour size in mice. The modified PDA micelles improved the anticancer effects of MGN-II in the A549 cell line only at a concentration of 16.0 μg mL-1 (IC50). In addition, following irradiation with UV light at 254 nm, the PDA micelles gave rise to an energy transfer from the fluorescent dye to the backbone of PDA micelles to enhance the imaging of living cells. Our results demonstrate that modified PDA micelles can not only be used in the treatment of tumors in vitro and in vivo in a simple and directed way, but also offer a new platform for designing functional liposomes to act as anticancer agents.Polydiacetylene (PDA) micelles have been widely used to deliver anticancer drugs in the treatment of a variety of tumours and for imaging living cells. In this study, we developed an effective strategy to directly conjugate magainin II (MGN-II) to the surface of PDA micelles using a fluorescent dye. These stable and well-defined PDA micelles had high cytotoxicity in cancer cell lines, and were able to reduce the tumour size in mice. The modified PDA micelles improved the anticancer effects of MGN-II in the A549 cell line only at a concentration of 16.0 μg mL-1 (IC50). In addition, following irradiation with UV light at 254 nm, the PDA micelles gave rise to an energy transfer from the fluorescent dye to the backbone of PDA micelles to enhance the imaging of living cells. Our results demonstrate that modified PDA micelles can not only be used in the treatment of tumors in vitro and in vivo in a simple and directed way, but also offer a new platform for

  4. Hepatic Bel-7402 Cell Proliferation on Different Phospholipid Surfaces

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    Phospholipids are believed to be important biomaterials.However, limited information is available on their cytocompatibilities.The objective of this study is to evaluate the effects of different phospholipids on the proliferation of hepatic Bel-7402 cells by comparing the adhesion, viability and proliferation of Bel-7402 cells cultured on different phospholipid surfaces.The cell adhesion, determined by counting the number of adhered cells to the surface, indicated that the cell adhesion was enhanced on charged phospolipid membranes.The cell viability evaluated by MTT[3 (4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium-bromide] showed that cells cultured on charged phospholipids have greater viability than those cultured on the control, while cells cultured on neutral phospholipids showed lower viability.The cell cycle analysis using flow cytometry demonstrated that S phase entry increased on charged phospholipids, while S phase entry decreased on neutral phospholipids.The results suggested that charged phospholipids, especially positively charged phospholipids, show better cytocompatibilities than neutral phospholipids to hepatic Bel-7402 cell.

  5. Polymer Micelles Laden Hydrogel Contact Lenses for Ophthalmic Drug Delivery.

    Science.gov (United States)

    Hu, Xiaohong; Tan, Huaping; Chen, Pin; Wang, Xin; Pang, Juan

    2016-06-01

    Hydrogel contact lens is an attractive drug carrier for the delivery of ophthalmic drugs. But limited drug loading capacity and burst release restricted its application in this field. Polymer micelle laden hydrogel contact lenses were designed for ophthalmic drug delivery in the work. β-CD/PAA/PEG ternary system was chosen to form polymer micelle. The micelle size could be adjusted by β-CD content and PAA/PEG concentration. The zeta potential of micelle was irrelevant to β-CD content, but influenced by PAA/PEG concentration. The absorbed drug concentration in micelle solution depended on both β-CD content and PAA/PEG concentration. Polymer micelle laden hydrogels were obtained by radical polymerization in situ. The transparency of polymer micelle laden hydrogel declined with PAA/PEG concentration increasing. The equilibrium water content and water loss showed that polymer micelle laden hydrogel with higher PAA/PEG concentration was in a higher swollen state. The dynamic viscoelastic properties howed that all polymer micelle laden hydrogels had some characteristics of crosslinked elastomers. The surface structure of freeze dried composite hydrogels was different from freeze dried pure hydrogel. The drug loading and releasing behaviors were detected to evaluate the drug loading and releasing capacity of hydrogels using orfloxacin and puerarin as model drugs. The results indicated the polymer micelle in hydrogel could hold or help to hold some ophthalmic drugs, and slow down orfloxacin release speed or keep puerarin stably stay for a time in hydrogels. In the end, it was found that the transparency of composite hydrogel became better after the hydrogel had been immersed in PBS for several weeks.

  6. Therapeutic surfactant-stripped frozen micelles

    Science.gov (United States)

    Zhang, Yumiao; Song, Wentao; Geng, Jumin; Chitgupi, Upendra; Unsal, Hande; Federizon, Jasmin; Rzayev, Javid; Sukumaran, Dinesh K.; Alexandridis, Paschalis; Lovell, Jonathan F.

    2016-05-01

    Injectable hydrophobic drugs are typically dissolved in surfactants and non-aqueous solvents which can induce negative side-effects. Alternatives like `top-down' fine milling of excipient-free injectable drug suspensions are not yet clinically viable and `bottom-up' self-assembled delivery systems usually substitute one solubilizing excipient for another, bringing new issues to consider. Here, we show that Pluronic (Poloxamer) block copolymers are amenable to low-temperature processing to strip away all free and loosely bound surfactant, leaving behind concentrated, kinetically frozen drug micelles containing minimal solubilizing excipient. This approach was validated for phylloquinone, cyclosporine, testosterone undecanoate, cabazitaxel and seven other bioactive molecules, achieving sizes between 45 and 160 nm and drug to solubilizer molar ratios 2-3 orders of magnitude higher than current formulations. Hypertonic saline or co-loaded cargo was found to prevent aggregation in some cases. Use of surfactant-stripped micelles avoided potential risks associated with other injectable formulations. Mechanistic insights are elucidated and therapeutic dose responses are demonstrated.

  7. Critical assessment of phospholipid measurement in amniotic fluid.

    Science.gov (United States)

    Badham, L P; Worth, H G

    1975-09-01

    We assessed several methods of inorganic phosphate assay for their suitability in estimating phospholipids in digested extracts of amniotic fluids. The extraction and digestion procedures used for phospholipids from amniotic fluid were also examined critically. The effect of contamination by blood or obstetric cream has been examined. Accordingly, we suggest a method for measuring total phospholipids in amniotic fluids, and results of it are compared with the lecithin/sphingomyelin ratio measurement in some clinical situations. PMID:1157310

  8. Motional Coherence in Fluid Phospholipid Membranes

    CERN Document Server

    Rheinstadter, Maikel C; Flenner, Elijah J; Bruening, Beate; Seydel, Tilo; Kosztin, Ioan

    2008-01-01

    We report a high energy-resolution neutron backscattering study, combined with in-situ diffraction, to investigate slow molecular motions on nanosecond time scales in the fluid phase of phospholipid bilayers of 1,2-dimyristoyl-sn-glycero-3-phoshatidylcholine (DMPC) and DMPC/40% cholesterol (wt/wt). A cooperative structural relaxation process was observed. From the in-plane scattering vector dependence of the relaxation rates in hydrogenated and deuterated samples, combined with results from a 0.1 microsecond long all atom molecular dynamics simulation, it is concluded that correlated dynamics in lipid membranes occurs over several lipid distances, spanning a time interval from pico- to nanoseconds.

  9. 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.

  10. Pressure-induced structural transition of nonionic micelles

    Indian Academy of Sciences (India)

    V K Aswal; R Vavrin; J Kohlbrecher; A G Wagh

    2008-11-01

    We report dynamic light scattering and small angle neutron scattering studies of the pressure-induced structural transition of nonionic micelles of surfactant polyoxyethylene 10 lauryl ether (C12E10) in the pressure range 0 to 2000 bar. Measurements have been performed on 1 wt% C12E10 in aqueous solution with and without the addition of KF. Micelles undergo sphere to lamellar structural transitions as the pressure is increased. On addition of KF, rod-like micelles exist at ambient pressure, which results in rod-like to lamellar structural transition at a much lower pressure in the presence of KF. Micellar structural transitions have been observed to be reversible.

  11. Self-assembly of micelles into designed networks

    Directory of Open Access Journals (Sweden)

    Pyatenko Alexander

    2007-01-01

    Full Text Available AbstractThe EO20PO70EO20(molecular weight 5800 amphiphile as a template is to form dispersed micelle structures. Silver nanoparticles, as inorganic precursors synthesized by a laser ablation method in pure water, are able to produce the highly ordered vesicles detected by TEM micrography. The thickness of the outer layer of a micelle, formed by the silver nanoparticles interacting preferentially with the more hydrophilic EO20block, was around 3.5 nm. The vesicular structure ensembled from micelles is due to proceeding to the mixture of cubic and hexagonal phases.

  12. Iron oxide nanoparticle-micelles (ION-micelles for sensitive (molecular magnetic particle imaging and magnetic resonance imaging.

    Directory of Open Access Journals (Sweden)

    Lucas W E Starmans

    Full Text Available BACKGROUND: Iron oxide nanoparticles (IONs are a promising nanoplatform for contrast-enhanced MRI. Recently, magnetic particle imaging (MPI was introduced as a new imaging modality, which is able to directly visualize magnetic particles and could serve as a more sensitive and quantitative alternative to MRI. However, MPI requires magnetic particles with specific magnetic properties for optimal use. Current commercially available iron oxide formulations perform suboptimal in MPI, which is triggering research into optimized synthesis strategies. Most synthesis procedures aim at size control of iron oxide nanoparticles rather than control over the magnetic properties. In this study, we report on the synthesis, characterization and application of a novel ION platform for sensitive MPI and MRI. METHODS AND RESULTS: IONs were synthesized using a thermal-decomposition method and subsequently phase-transferred by encapsulation into lipidic micelles (ION-Micelles. Next, the material and magnetic properties of the ION-Micelles were analyzed. Most notably, vibrating sample magnetometry measurements showed that the effective magnetic core size of the IONs is 16 nm. In addition, magnetic particle spectrometry (MPS measurements were performed. MPS is essentially zero-dimensional MPI and therefore allows to probe the potential of iron oxide formulations for MPI. ION-Micelles induced up to 200 times higher signal in MPS measurements than commercially available iron oxide formulations (Endorem, Resovist and Sinerem and thus likely allow for significantly more sensitive MPI. In addition, the potential of the ION-Micelle platform for molecular MPI and MRI was showcased by MPS and MRI measurements of fibrin-binding peptide functionalized ION-Micelles (FibPep-ION-Micelles bound to blood clots. CONCLUSIONS: The presented data underlines the potential of the ION-Micelle nanoplatform for sensitive (molecular MPI and warrants further investigation of the FibPep-ION-Micelle

  13. Photophysical study of a charge transfer oxazole dye in micelles: Role of surfactant headgroups

    Energy Technology Data Exchange (ETDEWEB)

    Maiti, Jyotirmay [Department of Chemistry, West Bengal State University, Barasat, Kolkata 700126 (India); Sarkar, Yeasmin; Parui, Partha Pratim [Department of Chemistry, Jadavpur University, Kolkata 700032 (India); Chakraborty, Sandipan [Department of Microbiology, University of Calcutta, Kolkata 700019 (India); Biswas, Suman [Department of Chemistry, West Bengal State University, Barasat, Kolkata 700126 (India); Das, Ranjan, E-mail: ranjan.das68@gmail.com [Department of Chemistry, West Bengal State University, Barasat, Kolkata 700126 (India)

    2015-07-15

    Photophysics of 5-(4′′-dimethylaminophenyl)-2-(4′-sulfophenyl)oxazole, sodium salt (DMO) which undergoes intramolecular charge transfer in the excited state was studied in micelles. In the cationic and the nonionic micelles, significantly higher fluorescence quantum yield is observed in comparison to the anionic micelles, due to much lower accessibility of DMO to the water molecules in the former micelles than the latter. Time-resolved fluorescence decays were characterized by a fast (τ{sub 1}) and a slow (τ{sub 2}) component of decay in all the micelles. The fast decay component (τ{sub 1}) increases significantly in going from the anionic micelles to the cationic micelles, because of the poorly hydrated headgroup region of the latter micelles compared to the former. Furthermore, much higher value of the slow component of decay (τ{sub 2}) is observed for the cationic and the neutral micelles than the anionic micelles. This is attributed to the increased penetration of water molecules into the micellar core of the anionic micelles compared to the cationic and the neutral micelles. - Highlights: • Photophysics of the fluorophore are remarkably different in the cationic and the anionic micelles. • Differential hydration of the surfactant headgroups gives rise to significantly different fluorescence quantum yield and lifetime in oppositely charged micelles. • Electrostatic interactions fine tune location of the fluorophore in the micelle–water interface of ionic micelles.

  14. Screening for the drug-phospholipid interaction: correlation to phospholipidosis

    DEFF Research Database (Denmark)

    Alakoskela, Juha-Matti; Vitovic, Pavol; Kinnunen, Paavo K J

    2009-01-01

    Phospholipid bilayers represent a complex, anisotropic environment fundamentally different from bulk oil or octanol, for instance. Even "simple" drug association to phospholipid bilayers can only be fully understood if the slab-of-hydrocarbon approach is abandoned and the complex, anisotropic pro...

  15. Structure and reactivity in amphiphile-water micelles

    International Nuclear Information System (INIS)

    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)

  16. Radiolabeling of liposomes and polymeric micelles with PET-isotopes

    DEFF Research Database (Denmark)

    Jensen, Andreas Tue Ingemann

    , that self‐assemble in water. Therapy with nanoparticles is hampered by often poor tumor accumulation, combined with massive uptake by macrophages in the liver and spleen. For this reason, visualizing nanoparticle pharmacokinetics in‐vivo is a valuable tool in the on‐going research. Such visualization can......), which mirrors the duration of nanoparticle pharmacokinetics. It is a metal and must be attached to polymeric micelles by covalently conjugated chelators. DOTA and CB‐TE2A are two such chelators, but DOTA is widely believed to be unstable in‐vivo. DOTA and CB‐TE2A were conjugated to triblock polymeric...... efficiency was achieved with both chelators (40‐70%). Some of the prepared micelles were found to exhibit gross instabilities, especially with raised temperature, which prevented their in-vivo use. Other micelles were stable and were investigated in xenographted mice. These micelles were 20‐45 nm...

  17. Sulfometuron incorporation in cationic micelles adsorbed on montmorillonite

    OpenAIRE

    Mishael, Y. G.; Undabeytia López, Tomás; Rytwo, Giora; Papahadjopoulos Sternberg, B.; Rubin, Baruch; Nir, Shlomo

    2002-01-01

    The aim of this study was to understand the interactions between alkylammonium cations present as monomers and micelles and a clay mineral, montmorillonite, to develop slow release formulations of anionic herbicides, such as sulfometuron (SFM) whose leaching in soils is an environmental and economic problem. In the proposed formulation the herbicide is incorporated in positively charged micelles of quaternary amine cations, which in turn adsorb on the negatively charged clay. The adsorption o...

  18. The Size Distribution of Casein Micelles in Camel Milk

    OpenAIRE

    Farah, Z.; Ruegg, M. W.

    1989-01-01

    The size distribution of casein micelles in camel milk has been determined by electron microscopy. Individual and pooled samples were cryo-fixed by rapid freezing and freeze-fractured. Electron micrographs of the freeze-fracture replica revealed a relatively broad size distribution, with an average micelle dimeter around 280 nm in the volume distribution curve. The distribution was significantly broader than that of the particles of cow's or human milk and showed a greater number of large ...

  19. Structure of strongly interacting polyelectrolyte diblock copolymer micelles

    OpenAIRE

    Korobko, A.V.; Jesse, W.; Lapp, A.; Egelhaaf, S. U.; van der Maarel, J. R. C.

    2004-01-01

    The structure of spherical micelles of the diblock poly(styrene-block-acrylic acid) [PS-b-PA] copolymer in water was investigated up to concentrations where the polyelectrolyte coronal layers have to shrink and/or interpenetrate in order to accommodate the micelles in the increasingly crowded volume. We obtained the partial structure factors pertaining to the core and corona density correlations with small angle neutron scattering (SANS) and contrast matching in the water. The counterion stru...

  20. A neutron scattering study of triblock copolymer micelles

    International Nuclear Information System (INIS)

    The thesis describes the neutron scattering experiments performed on poly(ethylene oxide)/poly(propylene oxide)/poly(ethylene oxide) triblock copolymer micelles in aqueous solution. The studies concern the non-ionic triblock copolymer P85 which consists of two outer segments of 25 monomers of ethylene oxide attached to a central part of 40 monomers of propylene oxide. The amphiphilic character of P85 leads to formation of various structures in aqueous solution such as spherical micelles, rod-like structures, and a BCC liquid-crystal mesophase of spherical micelles. The present investigations are centered around the micellar structures. In the first part of this thesis a model for the micelle is developed for which an analytical scattering form factor can be calculated. The micelle is modeled as a solid sphere with tethered Gaussian chains. Good agreement was found between small-angle neutron scattering experiments and the form factor of the spherical P85 micelles. Above 60 deg. C some discrepancies were found between the model and the data which is possibly due to an elongation of the micelles. The second part focuses on the surface-induced ordering of the various micellar aggregates in the P85 concentration-temperature phase diagram. In the spherical micellar phase, neutron reflection measurements indicated a micellar ordering at the hydrophilic surface of quartz. Extensive modeling was performed based on a hard sphere description of the micellar interaction. By convolution of the distribution of hard spheres at a hard wall, obtained from Monte Carlo simulations, and the projected scattering length density of the micelle, a numerical expression was obtained which made it possible to fit the data. The hard-sphere-hard-wall model gave an excellent agreement in the bulk micellar phase. However, for higher concentrations (25 wt % P85) close to the transition from the micellar liquid into a micellar cubic phase, a discrepancy was found between the model and the

  1. Preparation and characterization of magnetic thermosensitive fluorouracil micelles.

    Science.gov (United States)

    Zhang, Min; Jin, Xueqin; Gou, Guojing

    2016-01-01

    In this study, we synthesized P(NIPAM-co-DMAM)-b-PLA polymers with free radical polymerization and ring-opening addition polymerization, and immediately assembled 'dextran magnetic layered double hydroxide fluorouracil' (DMF) magnetic particles into the core of the amphiphilic polymer micelles with synchronous hydration and dialysis, to generate a magnetic thermosensitive fluorouracil drug delivery system. The basic properties of the micelle particles, such as the core-shell-type structure, size, and zeta potential, were studied with (1)H-NMR, FTIR, TEM, TGA, laser nanoparticle size analysis, and other characterization techniques. The thermosensitivity of the micelles was investigated by measuring parameters such as the lower critical solution temperature (LCST) and the relationship between the particle size variation and temperature. The drug release curves for the micelles at different temperatures were constructed with a dialysis method. The LCST of the triblock polymers was 42 °C. The particle sizes of the blank micelles and DMF-loaded micelles were 493.6 ± 1.8 nm and 464.9 ± 4.1 nm, respectively, at 25 °C. When the temperature was higher than LSCT, a contraction phase change in the micelle structure occurred, a significant characteristic of the core-shell-type structure, and reversible phase transition phenomena. The release behavior of the drug-loaded micelles showed obvious variations with temperature. Therefore, the magnetic thermosensitive fluorouracil drug delivery system has a good magnetic response and excellent temperature controlled release characteristics, so it can be used as a drug delivery system in magnetically and thermally targeted chemotherapy for tumors. PMID:26948946

  2. Predicting proton titration in cationic micelle and bilayer environments

    OpenAIRE

    Brian H. Morrow; Eike, David M.; Murch, Bruce P.; Koenig, Peter H.; Shen, Jana K.

    2014-01-01

    Knowledge of the protonation behavior of pH-sensitive molecules in micelles and bilayers has significant implications in consumer product development and biomedical applications. However, the calculation of pKa’s in such environments proves challenging using traditional structure-based calculations. Here we apply all-atom constant pH molecular dynamics with explicit ions and titratable water to calculate the pKa of a fatty acid molecule in a micelle of dodecyl trimethylammonium chloride and l...

  3. Regulation of lung surfactant phospholipid synthesis and metabolism.

    Science.gov (United States)

    Goss, Victoria; Hunt, Alan N; Postle, Anthony D

    2013-02-01

    The alveolar type II epithelial (ATII) cell is highly specialised for the synthesis and storage, in intracellular lamellar bodies, of phospholipid destined for secretion as pulmonary surfactant into the alveolus. Regulation of the enzymology of surfactant phospholipid synthesis and metabolism has been extensively characterised at both molecular and functional levels, but understanding of surfactant phospholipid metabolism in vivo in either healthy or, especially, diseased lungs is still relatively poorly understood. This review will integrate recent advances in the enzymology of surfactant phospholipid metabolism with metabolic studies in vivo in both experimental animals and human subjects. It will highlight developments in the application of stable isotope-labelled precursor substrates and mass spectrometry to probe lung phospholipid metabolism in terms of individual molecular lipid species and identify areas where a more comprehensive metabolic model would have considerable potential for direct application to disease states. PMID:23200861

  4. Applications of polymer micelles for imaging and drug delivery.

    Science.gov (United States)

    Movassaghian, Sara; Merkel, Olivia M; Torchilin, Vladimir P

    2015-01-01

    Polymeric micelles, self-assembling nano-constructs of amphiphilic copolymers, are widely considered as convenient nano-carriers for a variety of applications, such as diagnostic imaging, and drug and gene delivery. They have demonstrated a variety of favorable properties including biocompatibility, longevity, high stability in vitro and in vivo, capacity to effectively solubilize a variety of poorly soluble drugs, changing the release profile of the incorporated pharmaceutical agents, and the ability to accumulate in the target zone based on the enhanced permeability and retention effect. Moreover, additional functions can be imparted to the micelle-based delivery systems by engineering their surface for specific applications. Various targeting ligands can be attached for cell or intracellular accumulation at a site of interest. Also, the chelation or incorporation of imaging moieties into the micelle structure enables in vivo biodistribution studies. Moreover, pH-, thermo-, ultrasound-, enzyme- and light-sensitive block-copolymers allow for controlled micelle dissociation and triggered drug release in response to the pathological environment-specific stimuli and/or externally applied signals. The combination of these approaches can further improve specificity and efficacy of micelle-based drug delivery to promote the development of smart multifunctional micelles. PMID:25683687

  5. Structure and stability of complex coacervate core micelles with lysozyme.

    Science.gov (United States)

    Lindhoud, Saskia; Vries, Renko de; Norde, Willem; Stuart, Martien A Cohen

    2007-07-01

    Encapsulation of enzymes by polymers is a promising method to influence their activity and stability. Here, we explore the use of complex coacervate core micelles for encapsulation of enzymes. The core of the micelles consists of negatively charged blocks of the diblock copolymer PAA42PAAm417 and the positively charged homopolymer PDMAEMA150. For encapsulation, part of the positively charged homopolymer was replaced by the positively charged globular protein lysozyme. We have studied the formation, structure, and stability of the resulting micelles for three different mixing ratios of homopolymer and lysozyme: a system predominantly consisting of homopolymer, a system predominantly consisting of lysozyme, and a system where the molar ratio between the two positively charged molecules was almost one. We also studied complexes made of only lysozyme and PAA42PAAm417. Complex formation and the salt-induced disintegration of the complexes were studied using dynamic light-scattering titrations. Small-angle neutron scattering was used to investigate the structures of the cores. We found that micelles predominantly consisting of homopolymer are spherical but that complex coacervate core micelles predominantly consisting of lysozyme are nonspherical. The stability of the micelles containing a larger fraction of lysozyme is lower.

  6. Atomic Model and Micelle Dynamics of QS-21 Saponin

    Directory of Open Access Journals (Sweden)

    Conrado Pedebos

    2014-03-01

    Full Text Available QS-21 is a saponin extracted from Quillaja saponaria, widely investigated as a vaccine immunoadjuvant. However, QS-21 use is mainly limited by its chemical instability, significant variety in molecular composition and low tolerance dose in mammals. Also, this compound tends to form micelles in a concentration-dependent manner. Here, we aimed to characterize its conformation and the process of micelle formation, both experimentally and computationally. Therefore, molecular dynamics (MD simulations were performed in systems containing different numbers of QS-21 molecules in aqueous solution, in order to evaluate the spontaneous micelle formation. The applied methodology allowed the generation of micelles whose sizes were shown to be in high agreement with small-angle X-ray scattering (SAXS. Furthermore, the ester linkage between fucose and acyl chain was less solvated in the micellar form, suggesting a reduction in hydrolysis. This is the first atomistic interpretation of previous experimental data, the first micellar characterization of saponin micelles by SAXS and first tridimensional model of a micelle constituted of saponins, contributing to the understanding of the molecular basis of these compounds.

  7. The impact of phospholipids and phospholipid removal on bioanalytical method performance.

    Science.gov (United States)

    Carmical, Jennifer; Brown, Stacy

    2016-05-01

    Phospholipids (PLs) are a component of cellmembranes, biological fluids and tissues. These compounds are problematic for the bioanalytical chemist, especially when PLs are not the analytes of interest. PL interference with bioanalysis highly impacts reverse-phase chromatographic methods coupled with mass spectrometric detection. Phospholipids are strongly retained on hydrophobic columns, and can cause significant ionization suppression in the mass spectrometer, as they outcompete analyte molecules for ionization. Strategies for improving analyte detection in the presence of PLs are reviewed, including in-analysis modifications and sample preparation strategies. Removal of interfering PLs prior to analysis seems to be most effective atmoderating thematrix effects fromthese endogenous cellular components, and has the potential to simplify chromatography and improve column lifetime. Products targeted at PL removal for sample pre-treatment, as well as products that combine multiplemodes of sample preparation (i.e. Hybrid SPE), show significant promise inmediating the effect on PL interference in bioanalysis. PMID:26773720

  8. Computer simulations of phospholipid - membrane thermodynamic fluctuations

    DEFF Research Database (Denmark)

    Pedersen, U.R.; Peters, Günther H.j.; Schröder, T.B.;

    2008-01-01

    This paper reports all-atom computer simulations of five phospholipid membranes, DMPC, DPPC, DMPG, DMPS, and DMPSH, with a focus on the thermal equilibrium fluctuations of volume, energy, area, thickness, and order parameter. For the slow fluctuations at constant temperature and pressure (defined...... by averaging over 0.5 nanosecond) volume and energy exhibit strong correlation. These quantities on the other hand do not correlate significantly with area, thickness, or order parameter. The correlations are mainly reported for the fluid phase, but we also give results for the ordered (gel) phase of two...... membranes, showing a similar picture. The cause of the observed strong correlations is identified by splitting volume and energy into contributions from tails, heads, and water, showing that the slow volume-energy fluctuations derive from the tail region’s van der Waals interactions and are thus analogous...

  9. Molecular phospholipid films on solid supports

    DEFF Research Database (Denmark)

    Czolkos, Ilja; Jesorka, Aldo; Orwar, Owe

    2011-01-01

    Phospholipid membranes are versatile structures for mimicking biological surfaces. Bilayer and monolayer membranes can be formed on solid supports, leading to enhanced stability and accessibility of the biomimetic molecular film. This has facilitated functional studies of membrane proteins...... and aided the development of membrane-based applications in, for example, biosensing, self-assembled reaction kinetics and catalysis. Assembly and preparation of lipid films on supporting surfaces is a challenging engineering task with the goal of fabricating mechanically, chemically and thermodynamically...... stable lipid membranes. In this review, the current state of the art of molecularly thin lipid layer fabrication is presented with an emphasis on support materials, film formation mechanisms, characterisation methods, and applications....

  10. Langmuir films containing ibuprofen and phospholipids

    Science.gov (United States)

    Geraldo, Vananélia P. N.; Pavinatto, Felippe J.; Nobre, Thatyane M.; Caseli, Luciano; Oliveira, Osvaldo N.

    2013-02-01

    This study shows the incorporation of ibuprofen, an anti-inflammatory drug, in Langmuir monolayers as cell membrane models. Significant effects were observed for dipalmitoyl phosphatidyl choline (DPPC) monolayers with relevant changes in the elasticity of the monolayer. Dipalmitoyl phosphatidyl glycerol (DPPG) monolayers were affected by small concentrations of ibuprofen, from 1 to 5 mol%. For both types of monolayer, ibuprofen could penetrate into the hydrophobic part of the monolayer, which was confirmed with polarization-modulated infrared reflection-absorption spectroscopy (PM-IRRAS). Brewster angle microscopy (BAM) images showed that ibuprofen prevents the formation of large domains of DPPC. The pharmacological action should occur primarily with penetration of ibuprofen via electrically neutral phospholipid headgroups of the membrane.

  11. Conformation and Orientation of Phospholipid Molecule in Pure Phospholipid Monolayer During Compressing

    Institute of Scientific and Technical Information of China (English)

    XUE Weilan; WANG Dan; ZENG Zuoxiang; GAO Xuechao

    2013-01-01

    On the basis of energy conservation law and surface pressure isotherm,the conformation energy changes of dipalmitoylphosphatidylcholine(DPPC)and dipalmitoylphosphatidylglycerol(DPPG)in pure phospholipid monolayer at the air/water interface during compression are derived.The optimized conformations of phospholipids at absolute freedom state are simulated by Gaussian 98 software.Based on following assumptions:(1)the conformation energy change is mainly caused by the rotation of one special bond;(2)the atoms of glycerol near the water surface are active;(3)the rotation is motivated by hydrogen-bond action;(4)the rotation of bond is inertial,one simplified track of conformational change is suggested and the conformations of DPPC and DPPG at different states are determined by the plots of conformation energy change vs.dihedral angle.The thickness of the simulated phospholipid monolayer is consistent with published experimental result.According to molecular areas at different states,the molecular orientations in the compressing process are also developed.

  12. Morphology of polysorbate 80 (Tween 80) micelles in aqueous dimethyl sulfoxide solutions

    OpenAIRE

    Aizawa, Hideki

    2010-01-01

    The structures of micelles of the surfactant polysorbate 80 (Tween 80) in 0–50% aqueous dimethyl sulfoxide (DMSO) solutions (pH 7.2, ionic strength 2.44 mM) were investigated by means of small-angle X-ray scattering. At DMSO concentrations of 0–20%, core–shell cylinder micelles formed, and at 30–50% DMSO, core–shell discus micelles formed, that is, changing the hydrophobicity of the DMSO solvent mixture changed the micelles from core–shell cylinder micelles to core–shell discus micelles....

  13. Dielectric Analysis for the Spherical and Rodlike Micelle Aggregates Formed from a Gemini Surfactant: Driving Forces of Micellization and Stability of Micelles.

    Science.gov (United States)

    Wang, Shanshan; Zhao, Kongshuang

    2016-08-01

    The self-aggregation behavior of Gemini surfactant 12-2-12 (ethanediyl-1,2-bis(dimethyldodecylammonium bromide)) in water was investigated by dielectric relaxation spectroscopy (DRS) over a frequency range from 40 Hz to 110 MHz. Dielectric determination shows that well-defined spherical micelles formed when the concentration of the surfactant was above a critical micelle concentration CMC1 of 3 mM and rodlike micelles formed above CMC2, 16 mM. The formation mechanism of the spherical micelles and their transition mechanism to clubbed micelles were proposed by calculating the degree of counterion binding of the micelles. The interactions between the head groups and the hydrophobic chains of the surfactant led to the formation of the micelles, whereas the transition is mainly attributed to the interaction among the hydrophobic chains. By analyzing the dielectric relaxation observed at about 10(7) Hz based on the interface polarization theory, the permittivity and conductivity of micelle aggregates (spherical and clubbed) and volume fraction of micelles were calculated theoretically as well as the electrical properties of the solution medium. Furthermore, we also calculated the electrokinetic parameters of the micelle particle surface, surface conductivity, surface charge density, and zeta potential, using the relaxation parameters and phase parameters. On the basis of these results, the balance of forces controlling morphological transitions, interfacial electrokinetic properties, and the stability of the micelle aggregates was discussed. PMID:27396495

  14. Micelles as Soil and Water Decontamination Agents.

    Science.gov (United States)

    Shah, Afzal; Shahzad, Suniya; Munir, Azeema; Nadagouda, Mallikarjuna N; Khan, Gul Shahzada; Shams, Dilawar Farhan; Dionysiou, Dionysios D; Rana, Usman Ali

    2016-05-25

    Contaminated soil and water pose a serious threat to human health and ecosystem. For the treatment of industrial effluents or minimizing their detrimental effects, preventive and remedial approaches must be adopted prior to the occurrence of any severe environmental, health, or safety hazard. Conventional treatment methods of wastewater are insufficient, complicated, and expensive. Therefore, a method that could use environmentally friendly surfactants for the simultaneous removal of both organic and inorganic contaminants from wastewater is deemed a smart approach. Surfactants containing potential donor ligands can coordinate with metal ions, and thus such compounds can be used for the removal of toxic metals and organometallic compounds from aqueous systems. Surfactants form host-guest complexes with the hydrophobic contaminants of water and soil by a mechanism involving the encapsulation of hydrophobes into the self-assembled aggregates (micelles) of surfactants. However, because undefined amounts of surfactants may be released into the aqueous systems, attention must be paid to their own environmental risks as well. Moreover, surfactant remediation methods must be carefully analyzed in the laboratory before field implementation. The use of biosurfactants is the best choice for the removal of water toxins as such surfactants are associated with the characteristics of biodegradability, versatility, recovery, and reuse. This Review is focused on the currently employed surfactant-based soil and wastewater treatment technologies owing to their critical role in the implementation of certain solutions for controlling pollution level, which is necessary to protect human health and ensure the quality standard of the aquatic environment. PMID:27136750

  15. Nanoporous Silicified Phospholipids and Application to Controlled Glycolic Acid Release

    Directory of Open Access Journals (Sweden)

    Kang SangHwa

    2008-01-01

    Full Text Available Abstract This work demonstrates the synthesis and characterization of novel nanoporous silicified phospholipid bilayers assembled inorganic powders. The materials are obtained by silicification process with silica precursor at the hydrophilic region of phospholipid bilayers. This process involves the co-assembly of a chemically active phospholipids bilayer within the ordered porosity of a silica matrix and holds promise as a novel application for controlled drug release or drug containers with a high level of specificity and throughput. The controlled release application of the synthesized materials was achieved to glycolic acid, and obtained a zero-order release pattern due to the nanoporosity.

  16. TRANSDERMAL DELIVERY OF CYCLOSPORIN A SOLUBILIZED IN MIXED MICELLES THROUGH MICE SKIN%混合胶团增溶的环孢素A经小鼠皮肤的渗透作用

    Institute of Scientific and Technical Information of China (English)

    吴涛; 郭健新; 平其能; 金飞燕; 孙喜文

    2001-01-01

    AIM To investigate the transdermal delivery effects of cyclosporine A solubilized in mixed micelles composed of phospholipid and different surfactants. METHODS When applied onto the excised abdominal skin of the mice occlusively, the enhancing effects of various mixed micelles on the penetration of cyclosporin A were assessed by an in vitro permeation technique. In vivo study was carried out by topical application of sodium cholate-phospholipid mixed micelles onto the mice skin and drug blood concentration was detected. RESULTS In vitro, mixed micelles containing different surfactants displayed distinct permeability and corresponded to the following order: sodium cholate > sodium deoxycholate > Trition X-100 > Tween-20. In vivo, peak drug concentration was detected at 5 h and after that the concentration fell down slowly. CONCLUSION Mixed micelles were shown to be efficient carrier for the transdermal delivery of the lipophilic polypeptide when kept in solution during the application process.%目的研究由不同表面活性剂和磷脂所组成的混合胶团(mixed micelles)对环孢素A经小鼠皮肤给药的渗透促进作用。方法将含药混合胶团溶液封闭性应用于离体或在体小鼠皮肤,测定接收介质和血液中环孢素A含量。结果离体条件下,不同表面活性剂和磷脂所形成的混合胶团的皮肤渗透作用强度为:胆酸钠-磷脂混合胶团>脱氧胆酸钠-磷脂混合胶团>Triton X-100-磷脂混合胶团>Tween-20-磷脂混合胶团。在体条件下,用胆酸钠-磷脂混合胶团后,5 h血药浓度达峰值,随后血药浓度缓慢下降。结论混合胶团在水溶液状态下对大分子难溶药物环孢素A具有一定的皮肤促渗效果。

  17. Stability of complex coacervate core micelles containing metal coordination polymer.

    Science.gov (United States)

    Yan, Yun; de Keizer, Arie; Cohen Stuart, Martien A; Drechsler, Markus; Besseling, Nicolaas A M

    2008-09-01

    We report on the stability of complex coacervate core micelles, i.e., C3Ms (or PIC, BIC micelles), containing metal coordination polymers. In aqueous solutions these micelles are formed between charged-neutral diblock copolymers and oppositely charged coordination polymers formed from metal ions and bisligand molecules. The influence of added salt, polymer concentration, and charge composition was investigated by using light scattering and cryo-TEM techniques. The scattering intensity decreases strongly with increasing salt concentration until a critical salt concentration beyond which no micelles exist. The critical micelle concentration increases almost exponentially with the salt concentration. From the scattering results it follows that the aggregation number decreases with the square root of the salt concentration, but the hydrodynamic radius remains constant or increases slightly. It was concluded that the density of the core decreases with increasing ionic strength. This is in agreement with theoretical predictions and is also confirmed by cryo-TEM measurements. A complete composition diagram was constructed based on the composition boundaries obtained from light scattering titrations.

  18. Isolation of Phospholipid from Egg Yolk with Ultrasonic Separation Technology

    Directory of Open Access Journals (Sweden)

    Yu-mei Jia

    2014-03-01

    Full Text Available This study presented a new solution of isolation for phospholipid from egg yolks by ultrasonic wave. Degradation of phospholipid was discussed with the aggregation of micro-particles. The frequency of ultrasonic wave was 20 kHz. Lubricant was treated for 9 min under 0, 200, 400, 600W, respectively. It was showed that concentration of phospholipid reduced as ultrasonic power and time increased. Ultrasonic wave was useful for degradation of high molecular protein. Phospholipid secondary structure transforming was also observed, which was affected by ultrasonic wave. Suspension particles aggregated under the different ultrasonic wave condition. Content of the aggregation increased and volume of the aggregate reduced as ultrasonic treatment time increased.

  19. Herpes simplex virus 1 induces de novo phospholipid synthesis

    Energy Technology Data Exchange (ETDEWEB)

    Sutter, Esther [Electron Microscopy, Institute of Veterinary Anatomy, University of Zuerich (Switzerland); Oliveira, Anna Paula de; Tobler, Kurt [Electron microscopy, Institute of Virology, University of Zuerich (Switzerland); Schraner, Elisabeth M. [Electron Microscopy, Institute of Veterinary Anatomy, University of Zuerich (Switzerland); Sonda, Sabrina [Institute of Parasitology, University of Zuerich (Switzerland); Kaech, Andres [Center for Microscopy and Image Analysis, University of Zuerich (Switzerland); Lucas, Miriam S. [Electron Microscopy ETH Zuerich (EMEZ), Swiss Federal Institute of Technology, Zuerich (Switzerland); Ackermann, Mathias [Electron microscopy, Institute of Virology, University of Zuerich (Switzerland); Wild, Peter, E-mail: pewild@access.uzh.ch [Electron Microscopy, Institute of Veterinary Anatomy, University of Zuerich (Switzerland)

    2012-08-01

    Herpes simplex virus type 1 capsids bud at nuclear membranes and Golgi membranes acquiring an envelope composed of phospholipids. Hence, we measured incorporation of phospholipid precursors into these membranes, and quantified changes in size of cellular compartments by morphometric analysis. Incorporation of [{sup 3}H]-choline into both nuclear and cytoplasmic membranes was significantly enhanced upon infection. [{sup 3}H]-choline was also part of isolated virions even grown in the presence of brefeldin A. Nuclei expanded early in infection. The Golgi complex and vacuoles increased substantially whereas the endoplasmic reticulum enlarged only temporarily. The data suggest that HSV-1 stimulates phospholipid synthesis, and that de novo synthesized phospholipids are inserted into nuclear and cytoplasmic membranes to i) maintain membrane integrity in the course of nuclear and cellular expansion, ii) to supply membrane constituents for envelopment of capsids by budding at nuclear membranes and Golgi membranes, and iii) to provide membranes for formation of transport vacuoles.

  20. Phospholipids of the lung in normal, toxic, and diseased states

    Energy Technology Data Exchange (ETDEWEB)

    Akino, T.; Ohno, K.

    1981-01-01

    The highly pulmonary concentration of 1,2-dipalmitoyl-sn-glycerol-3-phosphorylcholine (dipalmitoyllecithin) and its implication as an important component of lung surfactant have promoted investigation of phospholipid metabolism in the lung. This review will set the contents including recent informations for better understanding of phospholipid metabolism of the lung in normal state (physiological significances of lung phospholipids, characteristics of phospholipids in lung tissue and alveolar washing, biosynthetic pathways of dipalmitoyllecithin, etc.) as well as in toxic states (pulmonary oxygen toxicity, etc.) and in diseased states (idiopathic respiratory distress syndrome, pulmonary alveolar proteinosis, etc.) Since our main concern has been to clarify the most important route for supplying dipalmitoyllecithin, this review will be focused upon the various biosynthetic pathways leading to the formation of different molecular species of lecithin and their potential significance in the normal, toxic, and diseased lungs.

  1. Biomimetic oral mucin from polymer micelle networks

    Science.gov (United States)

    Authimoolam, Sundar Prasanth

    Mucin networks are formed by the complexation of bottlebrush-like mucin glycoprotein with other small molecule glycoproteins. These glycoproteins create nanoscale strands that then arrange into a nanoporous mesh. These networks play an important role in ensuring surface hydration, lubricity and barrier protection. In order to understand the functional behavior in mucin networks, it is important to decouple their chemical and physical effects responsible for generating the fundamental property-function relationship. To achieve this goal, we propose to develop a synthetic biomimetic mucin using a layer-by-layer (LBL) deposition approach. In this work, a hierarchical 3-dimensional structures resembling natural mucin networks was generated using affinity-based interactions on synthetic and biological surfaces. Unlike conventional polyelectrolyte-based LBL methods, pre-assembled biotin-functionalized filamentous (worm-like) micelles was utilized as the network building block, which from complementary additions of streptavidin generated synthetic networks of desired thickness. The biomimetic nature in those synthetic networks are studied by evaluating its structural and bio-functional properties. Structurally, synthetic networks formed a nanoporous mesh. The networks demonstrated excellent surface hydration property and were able capable of microbial capture. Those functional properties are akin to that of natural mucin networks. Further, the role of synthetic mucin as a drug delivery vehicle, capable of providing localized and tunable release was demonstrated. By incorporating antibacterial curcumin drug loading within synthetic networks, bacterial growth inhibition was also demonstrated. Thus, such bioactive interfaces can serve as a model for independently characterizing mucin network properties and through its role as a drug carrier vehicle it presents exciting future opportunities for localized drug delivery, in regenerative applications and as bio

  2. Molecular Insights into Phospholipid -- NSAID Interactions

    Science.gov (United States)

    Babu Boggara, Mohan; Krishnamoorti, Ramanan

    2007-03-01

    Non steroidal anti inflammatory drugs (NSAIDs) e.g. Aspirin and Ibuprofen, with chronic usage cause gastro intestinal (GI) toxicity. It has been shown experimentally that NSAIDs pre-associated with phospholipids reduce the GI toxicity and also increase the therapeutic activity of these drugs compared to the unmodified ones. Using all atomistic simulations and two different methodologies, we studied the partitioning behavior of two model NSAIDs (Aspirin and Ibuprofen) as a function of pH and drug loading. The results from two methodologies are consistent in describing the equilibrium drug distribution in the bilayers. Additionally, the heterogeneity in density and polarity of the bilayer in the normal direction along with the fact that NSAIDs are amphiphilic (all of them have a carboxylic acid group and a non-polar part consisting of aromatic moieties), indicate that the diffusion mechanism in the bilayer is far different compared to the same in a bulk medium. This study summarizes the various effects of NSAIDs and their behavior inside the lipid bilayer both as a function of pH and drug concentration.

  3. Thermosensitive hydrogel containing dexamethasone micelles for preventing postsurgical adhesion in a repeated-injury model

    OpenAIRE

    Qinjie Wu; Ning Wang; Tao He; Jinfeng Shang; Ling Li; Linjiang Song; Xi Yang; Xia Li; Na Luo; Wenli Zhang; Changyang Gong

    2015-01-01

    Tissue adhesion is a common complication after surgery. In this work, a dexamethasone loaded polymeric micelles in thermosensitive hydrogel composite (Dex hydrogel) was prepared, which combined the anti-adhesion barrier with controlled release of anti-adhesion drug. Dexamethasone (Dex) was encapsulated in polymeric micelles (Dex micelles), and then the Dex micelles were loaded into biodegradable and thermosensitive hydrogel. The obtained Dex hydrogel showed a temperature-dependent sol-gel-sol...

  4. Role of Synthetic and Dimensional Synthetic Organic Chemistry in Block Copolymer Micelle Nanosensor Engineering

    OpenAIRE

    Ek, Pramod Kumar; Andresen, Thomas Lars; Almdal, Kristoffer

    2012-01-01

    This thesis investigated the role of amphiphilic triblock copolymer micelle nanomaterials in nanosensors, with emphasis on the synthesis of micelle particle sensors. The thesis is focused on the role of synthetic and dimensional synthetic organic chemistry in amphiphilic triblock core-shellcorona micelle based ratiometric fluorescence pH nanosensor fabrications. Two synthetic strategies such as post micelle modification and mixed micellisation (co-micellisation) were employed for pH nanosenso...

  5. Hydrolytic Degradation of Poly (ethylene oxide)-block-Polycaprolactone Worm Micelles

    OpenAIRE

    Geng, Yan; Discher, Dennis E.

    2005-01-01

    Spherical micelles and nanoparticles made with degradable polymers have been of great interest for therapeutic application, but degradation induced changes in a spherical morphology can be subtle and mechanism/kinetics appears poorly understood. Here, we report the first preparation of giant and flexible worm micelles self-assembled from degradable copolymer poly (ethylene oxide)-block-polycaprolactone. Such worm micelles spontaneously shorten to generate spherical micelles, triggered by poly...

  6. Liquid-liquid extraction by reversed micelles in biotechnological processes

    Directory of Open Access Journals (Sweden)

    Kilikian B. V.

    2000-01-01

    Full Text Available In biotechnology there is a need for new purification and concentration processes for biologically active compounds such as proteins, enzymes, nucleic acids, or cells that combine a high selectivity and biocompatibility with an easy scale-up. A liquid-liquid extraction with a reversed micellar phase might serve these purposes owing to its capacity to solubilize specific biomolecules from dilute aqueous solutions such as fermentation and cell culture media. Reversed micelles are aggregates of surfactant molecules containing an inner core of water molecules, dispersed in a continuous organic solvent medium. These reversed micelles are capable of selectively solubilizing polar compounds in an apolar solvent. This review gives an overview of liquid-liquid extraction by reversed micelles for a better understanding of this process.

  7. Artificial Self-Sufficient P450 in Reversed Micelles

    Directory of Open Access Journals (Sweden)

    Teruyuki Nagamune

    2010-04-01

    Full Text Available Cytochrome P450s are heme-containing monooxygenases that require electron transfer proteins for their catalytic activities. They prefer hydrophobic compounds as substrates and it is, therefore, desirable to perform their reactions in non-aqueous media. Reversed micelles can stably encapsulate proteins in nano-scaled water pools in organic solvents. However, in the reversed micellar system, when multiple proteins are involved in a reaction they can be separated into different micelles and it is then difficult to transfer electrons between proteins. We show here that an artificial self-sufficient cytochrome P450, which is an enzymatically crosslinked fusion protein composed of P450 and electron transfer proteins, showed micelle-size dependent catalytic activity in a reversed micellar system. Furthermore, the presence of thermostable alcohol dehydrogenase promoted the P450-catalyzed reaction due to cofactor regeneration.

  8. Enzymatically triggered multifunctional delivery system based on hyaluronic acid micelles

    KAUST Repository

    Deng, Lin

    2012-01-01

    Tumor targetability and stimuli responsivity of drug delivery systems (DDS) are key factors in cancer therapy. Implementation of multifunctional DDS can afford targetability and responsivity at the same time. Herein, cholesterol molecules (Ch) were coupled to hyaluronic acid (HA) backbones to afford amphiphilic conjugates that can self-assemble into stable micelles. Doxorubicin (DOX), an anticancer drug, and superparamagnetic iron oxide (SPIO) nanoparticles (NPs), magnetic resonance imaging (MRI) contrast agents, were encapsulated by Ch-HA micelles and were selectively released in the presence of hyaluronidase (Hyals) enzyme. Cytotoxicity and cell uptake studies were done using three cancer cell lines (HeLa, HepG2 and MCF7) and one normal cell line (WI38). Higher Ch-HA micelles uptake was seen in cancer cells versus normal cells. Consequently, DOX release was elevated in cancer cells causing higher cytotoxicity and enhanced cell death. © 2012 The Royal Society of Chemistry.

  9. From micelle supramolecular assemblies in selective solvents to isoporous membranes

    KAUST Repository

    Nunes, Suzana Pereira

    2011-08-16

    The supramolecular assembly of PS-b-P4VP copolymer micelles induced by selective solvent mixtures was used to manufacture isoporous membranes. Micelle order in solution was confirmed by cryo-scanning electron microscopy in casting solutions, leading to ordered pore morphology. When dioxane, a solvent that interacts poorly with the micelle corona, was added to the solution, polymer-polymer segment contact was preferential, increasing the intermicelle contact. Immersion in water gave rise to asymmetric porous membranes with exceptional pore uniformity and high porosity. The introduction of a small number of carbon nanotubes to the casting solution improved the membrane stability and the reversibility of the gate response in the presence of different pH values. © 2011 American Chemical Society.

  10. Multicompartment Micelles From π-Shaped ABC Block Copolymers

    Institute of Scientific and Technical Information of China (English)

    XIA Jun; ZHONG Chong-Li

    2007-01-01

    Dissipative particle dynamics simulations were performed on the morphology and structure of multicompartment micelles formed from n-shaped ABC block copolymers in water. The influences of chain architectures were studied in a systematic way, and a rich variety of morphologies were observed, such as spherical, wormlike,X-shaped, Y-shaped, ribbon-like, layered rod-like, layered disk-like, as well as network morphologies. The simulations show that the distance between the two grafts plays an important role in control of the morphology. Since π-shaped ABC block copolymers can be reduced to linear ABC and star ABC block copolymers, they are good model copolymers for studying the self-assembly of complex block copolymers into micelles. The knowledge obtained in this work as well as the new morphologies identified provide useful information for future rational design and synthesis of novel multicompartment micelles.

  11. Phospholipid Synthesis in Sindbis Virus-Infected Cells

    Science.gov (United States)

    Waite, Marilynn R. F.; Pfefferkorn, E. R.

    1970-01-01

    We investigated the metabolic requirements for the decrease in phospholipid synthesis previously observed by Pfefferkorn and Hunter in primary cultures of chick embryo fibroblasts infected with Sindbis virus. The incorporation of 32PO4 into all classes of phospholipids was found to decline at the same rate and to the same extent; thus, incorporation of 14C-choline into acid-precipitable form provided a convenient measure of phospholipid synthesis that was used in subsequent experiments. Experiments with temperature-sensitive mutants suggested that some viral ribonucleic acid (RNA) synthesis was essential for the inhibition of choline incorporation, but that functional viral structural proteins were not required. The reduction in phospholipid synthesis was probably a secondary effect of infection resulting from viral inhibition of the cellular RNA and protein synthesis. All three inhibitory effects required about the same amount of viral RNA synthesis; the inhibition of host RNA and protein synthesis began sooner than the decline in phospholipid synthesis; and both actinomycin D and cycloheximide inhibited 14C-choline incorporation in uninfected cells. In contrast, incorporation of 14C-choline into BHK-21 cells was not decreased by 10 hr of exposure to actinomycin D and declined only slowly after cycloheximide treatment. Growth of Sindbis virus in BHK cells did not cause the marked stimulation of phospholipid synthesis seen in picornavirus infections of other mammalian cells; however, inhibition was seen only late in infection. PMID:5530011

  12. Biomimetic surface modification of polyurethane with phospholipids grafted carbon nanotubes.

    Science.gov (United States)

    Tan, Dongsheng; Liu, Liuxu; Li, Zhen; Fu, Qiang

    2015-08-01

    To improve blood compatibility of polyurethane (PU), phospholipids grafted carbon nanotubes (CNTs) were prepared through zwitterion-mediated cycloaddition reaction and amide condensation, and then were added to the PU as fillers via solution mixing to form biomimetic surface. The properties of phospholipids grafted CNTs (CNT-PC) were investigated by thermal gravimetric analysis (TGA), X-ray photoelectron spectroscopy (XPS) and proton nuclear magnetic resonance ((1) H NMR). The results indicated that the phospholipids were grafted onto CNTs in high efficiency, and the hydrophilicity and dispersibility of the modified CNTs were improved effectively. The structures and properties of composites containing CNT-PC were investigated by optical microscope, XPS, and water contact angles. The results indicated that phospholipids were enriched on the surface with addition of 0.1 wt % of CNT-PC, which significantly reduced protein adsorption and platelet adhesion. The method of carrying phospholipids on the nanofiller to modify polymers has provided a promising way of constructing biomimetic phospholipid membrane on the surface to improve blood compatibility. PMID:25630300

  13. Controlled mixing of lanthanide(III) ions in coacervate core micelles.

    Science.gov (United States)

    Wang, Junyou; Velders, Aldrik H; Gianolio, Eliana; Aime, Silvio; Vergeldt, Frank J; Van As, Henk; Yan, Yun; Drechsler, Markus; de Keizer, Arie; Cohen Stuart, Martien A; van der Gucht, Jasper

    2013-05-01

    This article presents a facile strategy to combine Eu(3+) and Gd(3+) ions into coacervate core micelles in a controlled way with a statistical distribution of the ions. Consequently, the formed micelles show a high tunability between luminescence and relaxivity. These highly stable micelles present great potential for new materials, e.g. as bimodal imaging probes.

  14. Surface induced ordering of micelles at the solid-liquid interface

    DEFF Research Database (Denmark)

    Gerstenberg, M.C.; Pedersen, J.S.; Smith, G.S.

    1998-01-01

    The surface induced ordering of triblock copolymer micelles in aqueous solution was measured with neutron reflectivity far above the critical micelle concentration. The scattering length density profiles showed a clear indication of ordered layers of micelles perpendicular to a quartz surface. Th...

  15. COMPARISON OF DRUG DELIVERY PROPERTIES OF PEG-b-PDHPC MICELLES WITH DIFFERENT COMPOSITIONS

    Institute of Scientific and Technical Information of China (English)

    Chun-yan Long; Ming-ming Sheng; Bin He; Yao Wu; Gang Wang; Zhong-wei Gu

    2012-01-01

    An anti-tumor drug doxombicin was encapsulated in micelles of poly(ethylene glycol)-b-poly(2,2-dihydroxyl-methyl propylene carbonate) (PEG-b-PDHPC) diblock copolymers.The morphology of both blank micelles and drug loaded micelles was characterized by TEM.The in vitro drug release profiles of micelles were investigated.The cytotoxicity of the micelles was evaluated by incubating with Hela tumor cells and 3T3 fibroblasts.The drug loaded micelles were co-cultured with HepG2 cells to evaluate the in vitro anti-tumor efficacies.The results showed that the mean sizes of both micelles with different copolymer compositions increased after being loaded with drugs.The drug release rate of PEG45-b-PDHPC34 micelles was faster than that of rnPEG114-b-PDHPC26 micelles.Both of the two block copolymers were non-toxic.The confocal laser scanning microscopy and flow cytometry results showed that both the drug loaded micelles could be internalized efficiently in HepG2 cells.The PEG45-b-PDHPC34 micelles exhibited higher anti-tumor activity comparing to mPEG114-b-PDHPC26 micelles.

  16. Novel micelle formulations to increase cutaneous bioavailability of azole antifungals.

    Science.gov (United States)

    Bachhav, Y G; Mondon, K; Kalia, Y N; Gurny, R; Möller, M

    2011-07-30

    Efficient topical drug administration for the treatment of superficial fungal infections would deliver the therapeutic agent to the target compartment and reduce the risk of systemic side effects. However, the physicochemical properties of the commonly used azole antifungals make their formulation a considerable challenge. The objective of the present investigation was to develop aqueous micelle solutions of clotrimazole (CLZ), econazole nitrate (ECZ) and fluconazole (FLZ) using novel amphiphilic methoxy-poly(ethylene glycol)-hexyl substituted polylactide (MPEG-hexPLA) block copolymers. The CLZ, ECZ and FLZ formulations were characterized with respect to drug loading and micelle size. The optimal drug formulation was selected for skin transport studies that were performed using full thickness porcine and human skin. Penetration pathways and micellar distribution in the skin were visualized using fluorescein loaded micelles and confocal laser scanning microscopy. The hydrodynamic diameters of the azole loaded micelles were between 70 and 165nm and the corresponding number weighted diameters (d(n)) were 30 to 40nm. Somewhat surprisingly, the lowest loading efficiency (13-fold higher than that from Pevaryl® cream (22.8±3.8 and 1.7±0.6μg/cm(2), respectively). A significant enhancement was also observed with human skin; the amounts of ECZ deposited were 11.3±1.6 and 1.5±0.4μg/cm(2), respectively (i.e., a 7.5-fold improvement in delivery). Confocal laser scanning microscopy images supported the hypothesis that the higher delivery observed in porcine skin was due to a larger contribution of the follicular penetration pathway. In conclusion, the significant increase in ECZ skin deposition achieved using the MPEG-dihexPLA micelles demonstrates their ability to improve cutaneous drug bioavailability; this may translate into improved clinical efficacy in vivo. Moreover, these micelle systems may also enable targeting of the hair follicle and this will be investigated

  17. Fluorescent supramolecular micelles for imaging-guided cancer therapy

    Science.gov (United States)

    Sun, Mengmeng; Yin, Wenyan; Dong, Xinghua; Yang, Wantai; Zhao, Yuliang; Yin, Meizhen

    2016-02-01

    A novel smart fluorescent drug delivery system composed of a perylene diimide (PDI) core and block copolymer poly(d,l-lactide)-b-poly(ethyl ethylene phosphate) is developed and named as PDI-star-(PLA-b-PEEP)8. The biodegradable PDI-star-(PLA-b-PEEP)8 is a unimolecular micelle and can self-assemble into supramolecular micelles, called as fluorescent supramolecular micelles (FSMs), in aqueous media. An insoluble drug camptothecin (CPT) can be effectively loaded into the FSMs and exhibits pH-responsive release. Moreover, the FSMs with good biocompatibility can also be employed as a remarkable fluorescent probe for cell labelling because the maximum emission of PDI is beneficial for bio-imaging. The flow cytometry and confocal laser scanning microscopy analysis demonstrate that the micelles are easily endocytosed by cancer cells. In vitro and in vivo tumor growth-inhibitory studies reveal a better therapeutic effect of FSMs after CPT encapsulation when compared with the free CPT drug. The multifunctional FSM nanomedicine platform as a nanovehicle has great potential for fluorescence imaging-guided cancer therapy.A novel smart fluorescent drug delivery system composed of a perylene diimide (PDI) core and block copolymer poly(d,l-lactide)-b-poly(ethyl ethylene phosphate) is developed and named as PDI-star-(PLA-b-PEEP)8. The biodegradable PDI-star-(PLA-b-PEEP)8 is a unimolecular micelle and can self-assemble into supramolecular micelles, called as fluorescent supramolecular micelles (FSMs), in aqueous media. An insoluble drug camptothecin (CPT) can be effectively loaded into the FSMs and exhibits pH-responsive release. Moreover, the FSMs with good biocompatibility can also be employed as a remarkable fluorescent probe for cell labelling because the maximum emission of PDI is beneficial for bio-imaging. The flow cytometry and confocal laser scanning microscopy analysis demonstrate that the micelles are easily endocytosed by cancer cells. In vitro and in vivo tumor growth

  18. Nanoparticle self-assembly in mixtures of phospholipids with styrene/maleic acid copolymers or fluorinated surfactants

    Science.gov (United States)

    Vargas, Carolyn; Arenas, Rodrigo Cuevas; Frotscher, Erik; Keller, Sandro

    2015-12-01

    Self-assembling nanostructures in aqueous mixtures of bilayer-forming lipids and micelle-forming surfactants are relevant to in vitro studies on biological and synthetic membranes and membrane proteins. Considerable efforts are currently underway to replace conventional detergents by milder alternatives such as styrene/maleic acid (SMA) copolymers and fluorinated surfactants. However, these compounds and their nanosized assemblies remain poorly understood as regards their interactions with lipid membranes, particularly, the thermodynamics of membrane partitioning and solubilisation. Using 19F and 31P nuclear magnetic resonance spectroscopy, static and dynamic light scattering, and isothermal titration calorimetry, we have systematically investigated the aggregational state of a zwitterionic bilayer-forming phospholipid upon exposure to an SMA polymer with a styrene/maleic acid ratio of 3 : 1 or to a fluorinated octyl phosphocholine derivative called F6OPC. The lipid interactions of SMA(3 : 1) and F6OPC can be thermodynamically conceptualised within the framework of a three-stage model that treats bilayer vesicles, discoidal or micellar nanostructures, and the aqueous solution as distinct pseudophases. The exceptional solubilising power of SMA(3 : 1) is reflected in very low membrane-saturating and solubilising polymer/lipid molar ratios of 0.10 and 0.15, respectively. Although F6OPC saturates bilayers at an even lower molar ratio of 0.031, this nondetergent does not solubilise lipids even at >1000-fold molar excess, thus highlighting fundamental differences between these two types of mild membrane-mimetic systems. We rationalise these findings in terms of a new classification of surfactants based on bilayer-to-micelle transfer free energies and discuss practical implications for membrane-protein research.Self-assembling nanostructures in aqueous mixtures of bilayer-forming lipids and micelle-forming surfactants are relevant to in vitro studies on biological and

  19. Binding of chloroquine to ionic micelles: Effect of pH and micellar surface charge

    Energy Technology Data Exchange (ETDEWEB)

    Souza Santos, Marcela de, E-mail: marcelafarmausp77@gmail.com [Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Avenida do Café, s/n, Ribeirão Preto, São Paulo 14040-903 (Brazil); Perpétua Freire de Morais Del Lama, Maria, E-mail: mpemdel@fcfrp.usp.br [Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Avenida do Café, s/n, Ribeirão Preto, São Paulo 14040-903 (Brazil); Instituto Nacional de Ciência e Tecnologia de Bioanalítica, Departamento de Química Analítica, Universidade Estadual de Campinas, Cidade Universitária Zeferino Vaz, s/n, Campinas, São Paulo 13083-970 (Brazil); Siuiti Ito, Amando, E-mail: amandosi@ffclrp.usp.br [Departamento de Física, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Avenida Bandeirantes, 3900, Ribeirão Preto, São Paulo 14040-901 (Brazil); and others

    2014-03-15

    The pharmacological action of chloroquine relies on its ability to cross biological membranes in order to accumulate inside lysosomes. The present work aimed at understanding the basis for the interaction between different chloroquine species and ionic micelles of opposite charges, the latter used as a simple membrane model. The sensitivity of absorbance and fluorescence of chloroquine to changes in its local environment was used to probe its interaction with cetyltrimethylammonium micelles presenting bromide (CTAB) and sulfate (CTAS) as counterions, in addition to dodecyl sulfate micelles bearing sodium (SDS) and tetramethylammonium (TMADS) counterions. Counterion exchange was shown to have little effect on drug–micelle interaction. Chloroquine first dissociation constant (pKa{sub 1}) shifted to opposite directions when anionic and cationic micelles were compared. Chloroquine binding constants (K{sub b}) revealed that electrostatic forces mediate charged drug–micelle association, whereas hydrophobic interactions allowed neutral chloroquine to associate with anionic and cationic micelles. Fluorescence quenching studies indicated that monoprotonated chloroquine is inserted deeper into the micelle surface of anionic micelles than its neutral form, the latter being less exposed to the aqueous phase when associated with cationic over anionic assemblies. The findings provide further evidence that chloroquine–micelle interaction is driven by a tight interplay between the drug form and the micellar surface charge, which can have a major effect on the drug biological activity. -- Highlights: • Chloroquine (CQ) pKa{sub 1} increased for SDS micelles and decreased for CTAB micelles. • CQ is solubilized to the surface of both CTAB and SDS micelles. • Monoprotonated CQ is buried deeper into SDS micelles than neutral CQ. • Neutral CQ is less exposed to aqueous phase in CTAB over SDS micelles. • Local pH and micellar surface charge mediate interaction of CQ with

  20. Digestion of phospholipids after secretion of bile into the duodenum changes the phase behavior of bile components.

    Science.gov (United States)

    Birru, Woldeamanuel A; Warren, Dallas B; Ibrahim, Ahmed; Williams, Hywel D; Benameur, Hassan; Porter, Christopher J H; Chalmers, David K; Pouton, Colin W

    2014-08-01

    Bile components play a significant role in the absorption of dietary fat, by solubilizing the products of fat digestion. The absorption of poorly water-soluble drugs from the gastrointestinal tract is often enhanced by interaction with the pathways of fat digestion and absorption. These processes can enhance drug absorption. Thus, the phase behavior of bile components and digested lipids is of great interest to pharmaceutical scientists who seek to optimize drug solubilization in the gut lumen. This can be achieved by dosing drugs after food or preferably by formulating the drug in a lipid-based delivery system. Phase diagrams of bile salts, lecithin, and water have been available for many years, but here we investigate the association structures that occur in dilute aqueous solution, in concentrations that are present in the gut lumen. More importantly, we have compared these structures with those that would be expected to be present in the intestine soon after secretion of bile. Phosphatidylcholines are rapidly hydrolyzed by pancreatic enzymes to yield equimolar mixtures of their monoacyl equivalents and fatty acids. We constructed phase diagrams that model the association structures formed by the products of digestion of biliary phospholipids. The micelle-vesicle phase boundary was clearly identifiable by dynamic light scattering and nephelometry. These data indicate that a significantly higher molar ratio of lipid to bile salt is required to cause a transition to lamellar phase (i.e., liposomes in dilute solution). Mixed micelles of digested bile have a higher capacity for solubilization of lipids and fat digestion products and can be expected to have a different capacity to solubilize lipophilic drugs. We suggest that mixtures of lysolecithin, fatty acid, and bile salts are a better model of molecular associations in the gut lumen, and such mixtures could be used to better understand the interaction of drugs with the fat digestion and absorption pathway.

  1. Role of Synthetic and Dimensional Synthetic Organic Chemistry in Block Copolymer Micelle Nanosensor Engineering

    DEFF Research Database (Denmark)

    Ek, Pramod Kumar

    This thesis investigated the role of amphiphilic triblock copolymer micelle nanomaterials in nanosensors, with emphasis on the synthesis of micelle particle sensors. The thesis is focused on the role of synthetic and dimensional synthetic organic chemistry in amphiphilic triblock core...... micelles. Shell cross-linking on PEG-b-PAEMA-b-PS micelles was performed by amidation reactions between the amino groups of PAEMA blocks using a di-carboxylic acid cross-linker. Also a dendritic cross-linker based click chemistry was used to stabilize the PEG-b-PAEMA-b-PES micelle having click readied PES...

  2. Biodegradable polymeric micelle-encapsulated doxorubicin suppresses tumor metastasis by killing circulating tumor cells

    Science.gov (United States)

    Deng, Senyi; Wu, Qinjie; Zhao, Yuwei; Zheng, Xin; Wu, Ni; Pang, Jing; Li, Xuejing; Bi, Cheng; Liu, Xinyu; Yang, Li; Liu, Lei; Su, Weijun; Wei, Yuquan; Gong, Changyang

    2015-03-01

    Circulating tumor cells (CTCs) play a crucial role in tumor metastasis, but it is rare for any chemotherapy regimen to focus on killing CTCs. Herein, we describe doxorubicin (Dox) micelles that showed anti-metastatic activity by killing CTCs. Dox micelles with a small particle size and high encapsulation efficiency were obtained using a pH-induced self-assembly method. Compared with free Dox, Dox micelles exhibited improved cytotoxicity, apoptosis induction, and cellular uptake. In addition, Dox micelles showed a sustained release behavior in vitro, and in a transgenic zebrafish model, Dox micelles exhibited a longer circulation time and lower extravasation from blood vessels into surrounding tissues. Anti-tumor and anti-metastatic activities of Dox micelles were investigated in transgenic zebrafish and mouse models. In transgenic zebrafish, Dox micelles inhibited tumor growth and prolonged the survival of tumor-bearing zebrafish. Furthermore, Dox micelles suppressed tumor metastasis by killing CTCs. In addition, improved anti-tumor and anti-metastatic activities were also confirmed in mouse tumor models, where immunofluorescent staining of tumors indicated that Dox micelles induced more apoptosis and showed fewer proliferation-positive cells. There were decreased side effects in transgenic zebrafish and mice after administration of Dox micelles. In conclusion, Dox micelles showed stronger anti-tumor and anti-metastatic activities and decreased side effects both in vitro and in vivo, which may have potential applications in cancer therapy.

  3. Polymeric micelles in anticancer therapy : targeting, imaging and triggered release

    NARCIS (Netherlands)

    Oerlemans, Chris; Bult, Wouter; Bos, Mariska; Storm, Gert; Nijsen, J Frank W; Hennink, Wim E

    2010-01-01

    Micelles are colloidal particles with a size around 5-100 nm which are currently under investigation as carriers for hydrophobic drugs in anticancer therapy. Currently, five micellar formulations for anticancer therapy are under clinical evaluation, of which Genexol-PM has been FDA approved for use

  4. Complex coacervate core micelles from iron-based coordination polymers.

    Science.gov (United States)

    Wang, Junyou; de Keizer, Arie; Fokkink, Remco; Yan, Yun; Cohen Stuart, Martien A; van der Gucht, Jasper

    2010-07-01

    Complex coacervate core micelles (C3Ms) from cationic poly(N-methyl-2-vinyl-pyridinium iodide)-b-poly(ethylene oxide) (P2MVP(41)-b-PEO(205)) and anionic iron coordination polymers are investigated in the present work. Micelle formation is studied by light scattering for both Fe(II)- and Fe(III)-containing C3Ms. At the stoichiometric charge ratio, both Fe(II)-C3Ms and Fe(III)-C3Ms are stable for at least 1 week at room temperature. Excess of iron coordination polymers has almost no effect on the formed Fe(II)-C3Ms and Fe(III)-C3Ms, whereas excess of P2MVP(41)-b-PEO(205) copolymers in the solution can dissociate the formed micelles. Upon increasing salt concentration, the scattering intensity decreases. This decrease is due to both a decrease in the number of micelles (or an increase in CMC) and a decrease in aggregation number. The salt dependence of the CMC and the aggregation number is explained using a scaling argument for C3M formation. Compared with Fe(II)-C3Ms, Fe(III)-C3Ms have a lower CMC and a higher stability against dissociation by added salt.

  5. Dynamics of Chain Exchange in Block Copolymer Micelles

    Science.gov (United States)

    Lodge, Timothy

    Block copolymer micelles are rarely at equilibrium. The primary reason is the large number of repeat units in the insoluble block, Ncore, which makes the thermodynamic penalty for extracting a single chain (``unimer exchange'') substantial. As a consequence, the critical micelle concentration (CMC) is rarely accessed experimentally; however, in the proximity of a critical micelle temperature (CMT), equilibration is possible. We have been using time-resolved small angle neutron scattering (TR-SANS) to obtain a detailed picture of the mechanisms and time scales for chain exchange, at or near equilibrium. Our model system is poly(styrene)-block-poly(ethylene-alt-propylene)) (PS-PEP), in the PEP-selective solvent squalane (C30H62) . Equivalent micelles with either normal (hPS) or perdeuterated (dPS) cores are initially mixed in a blend of isotopically substituted squalane, designed to contrast-match a 50:50 hPS:dPS core. Samples are then annealed at a target temperature, and chain exchange is revealed quantitatively by the temporal decay in scattered intensity. The rate of exchange as function of concentration, temperature, Ncore, Ncorona, and chain architecture (diblock versus triblock) will be discussed.

  6. In vivo toxicity of cationic micelles and liposomes

    DEFF Research Database (Denmark)

    Knudsen, Kristina Bram; Northeved, Helle; Ek, Pramod Kumar;

    2015-01-01

    This study investigated toxicity of nanocarriers comprised of cationic polymer and lipid components often used in gene and drug delivery, formulated as cationic micelles and liposomes. Rats were injected intravenously with 10, 25 or 100 mg/kg and sacrificed after 24 or 48 h, or 24 h after the las...

  7. Ultrafast energy transfer in water-AOT reverse micelles

    NARCIS (Netherlands)

    Cringus, Dan; Bakulin, Artem; Lindner, Joerg; Voehringer, Peter; Pshenichnikov, Maxim S.; Wiersma, Douwe A.

    2007-01-01

    A spectroscopic investigation of the vibrational dynamics of water in a geometrically confined environment is presented. Reverse micelles of the ternary microemulsion H2O/AOT/n-octane (AOT = bis-2-ethylhexyl sulfosuccinate or aerosol-OT) with diameters ranging from 1 to 10 nm are used as a model sys

  8. The Critical Micelle Concentration of Asphaltenes as Measured by Calorimetry

    DEFF Research Database (Denmark)

    Andersen, Simon Ivar; Christensen, S. D.

    2000-01-01

    Micellization of asphaltenes in solution has been investigated using a micro calorimetric titration procedure (Andersen, S. I.; Birdi, K. S. J Colloid Interface Sci. 1991, 142, 497). The method uses the analysis of heat of dissociation and dilution of asphaltene micelles when a pure solvent (or s...

  9. Transport of charged Aerosol OT inverse micelles in nonpolar liquids.

    Science.gov (United States)

    Karvar, Masoumeh; Strubbe, Filip; Beunis, Filip; Kemp, Roger; Smith, Ashley; Goulding, Mark; Neyts, Kristiaan

    2011-09-01

    Surfactants such as Aerosol OT (AOT) are commonly used to stabilize and electrically charge nonpolar colloids in devices such as electronic ink displays. The electrical behavior of such devices is strongly influenced by the presence of charged inverse micelles, formed by excess surfactant that does not cover the particles. The presence of charged inverse micelles results in increased conductivity of the solution, affecting both the energy consumption of the device and its switching characteristics. In this work, we use transient current measurements to investigate the electrical properties of suspensions of the surfactant Aerosol OT in dodecane. No particles are added, to isolate the effect of excess surfactant. The measured currents upon application of a voltage step are found to be exponentially decaying, and can be described by an analytical model based on an equivalent electric circuit. This behavior is physically interpreted, first by the high generation rate of charged inverse micelles giving the suspension resistor like properties, and second by the buildup of layers of charged inverse micelles at both electrodes, acting as capacitors. The model explains the measurements over a large range of surfactant concentrations, applied voltages, and device thicknesses. PMID:21728309

  10. Monitoring the aggregation of single casein micelles using fluorescence microscopy

    DEFF Research Database (Denmark)

    Bomholt, Julie; Moth-Poulsen, Kasper; Harboe, Marianne;

    2011-01-01

    The aggregation of casein micelles (CMs) induced by milk-clotting enzymes is a process of fundamental importance in the dairy industry for cheese production; however, it is not well characterized on the nanoscale. Here we enabled the monitoring of the kinetics of aggregation between single CMs (3...

  11. Enhanced cytotoxicity of TATp-bearing paclitaxel-loaded micelles in vitro and in vivo

    Science.gov (United States)

    Sawant, Rupa R.; Torchilin, Vladimir P.

    2009-01-01

    Cell-penetrating peptide (TATp) was attached to the distal tips of polyethylene glycol (PEG) moieties of polyethyleneglycol-phosphatidylethanolamine (PEG-PE) micelles loaded with paclitaxel (PCT). The TATp-modified micelles demonstrated an increased interaction with cancer cells compared to non-modified micelles resulting in a significant increase of the in vitro cytotoxicity to different cancer cells. TATp-modified PCT-loaded micelles were administered intratumorally in mice and the induction of apoptosis in tumor cells was studied after 48h with the Terminal Deoxynucleotidyl Transferase Biotin-dUTP Nick End Labeling (TUNEL) assay using free PCT and TATp-free PCT-loaded PEG-PE micelles as controls. A significant apoptotic cell death was observed in tumors treated with PCT-loaded micelles modified with TATp, while the treatment with free PCT or with non-modified PCT-loaded micelles resulted in much smaller number of TUNEL-positive cells within tumors. PMID:19446767

  12. Reverse micelles as suitable microreactor for increased biohydrogen production

    Energy Technology Data Exchange (ETDEWEB)

    Pandey, Anjana [Nanotechnology and Molecular Biology Laboratory, Centre of Biotechnology, University of Allahabad, Allahabad 211002 (India); Pandey, Ashutosh [Centre of Energy Studies, MNNIT, Allahabad 211004 (India)

    2008-01-15

    Reverse micelles have been shown to act as efficient microreactors for enzymic reactions and whole cell entrapment in organic (non-aqueous) media wherein the reactants are protected from denaturation by the surrounding organic solvent. These micelles are thermodynamically stable, micrometer sized water droplets dispersed in an organic phase by a surfactant. It has been observed that when whole cells of photosynthetic bacteria (Rhodopseudomonas sphaeroides or Rhodobacter sphaeroides 2.4.1) are entrapped inside these reverse micelles, the H{sub 2} production enhanced from 25 to 35 folds. That is, 1.71mmol(mgprotein){sup -1}h{sup -1} in case of R. sphaeroides which is 25 fold higher in benzene-sodium lauryl sulfate reverse micelles. Whereas, in case of R. sphaeroides 2.4.1 the H{sub 2} production was increased by 35 fold within AOT-isooctane reverse micelles i.e. 11.5mmol(mgprotein){sup -1}h{sup -1}. The observations indicate that the entrapment of whole cells of microbes within reverse micelles provides a novel and efficient technique to produce hydrogen by the inexhaustible biological route. The two microorganisms R. sphaeroides 2.4.1 (a photosynthetic bacteria) and Citrobacter Y19 (a facultative anaerobic bacteria) together are also entrapped within AOT-isooctane and H{sub 2} production was measured i.e. 69mmol(mgprotein){sup -1}h{sup -1}. The nitrogenase enzyme responsible for hydrogen production by R. sphaeroides/R. sphaeroides 2.4.1 cells is oxygen sensitive, and very well protected within reverse micelles by the use of combined approach of two cells (R. sphaeroides 2.4.1 and Citrobacter Y19). In this case glucose present in the medium of Citrobacter Y19 serves double roles in enhancing the sustained production rate of hydrogen. Firstly, it quenches the free O{sub 2}liberated as a side product of reaction catalyzed by nitrogenase, which is O{sub 2} labile. Secondly, organic acid produced by this reaction is utilized by the Citrobacter Y19 as organic substrate in

  13. Solubilization of beclomethasone dipropionate in sterically stabilized phospholipid nanomicelles (SSMs: physicochemical and in vitro evaluations

    Directory of Open Access Journals (Sweden)

    Peh KK

    2012-02-01

    Full Text Available Mohanad Naji Sahib, Shaymaa Abdalwahed Abdulameer, Yusrida Darwis, Kok Khiang Peh, Yvonne Tze Fung TanSchool of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, MalaysiaBackground: The local treatment of lung disorders such as asthma and chronic obstructive pulmonary disease via pulmonary drug delivery offers many advantages over oral or intravenous routes of administration. This is because direct deposition of a drug at the diseased site increases local drug concentrations, which improves the pulmonary receptor occupancy and reduces the overall dose required, therefore reducing the side effects that result from high drug doses. From a clinical point of view, although jet nebulizers have been used for aerosol delivery of water-soluble compounds and micronized suspensions, their use with hydrophobic drugs has been inadequate.Aim: To evaluate the feasibility of sterically stabilized phospholipid nanomicelles (SSMs loaded with beclomethasone dipropionate (BDP as a carrier for pulmonary delivery.Methods: 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 5000 polymeric micelles containing BDP (BDP-SSMs were prepared by the coprecipitation and reconstitution method, and the physicochemical and in vitro characteristics of BDP-SSMs were investigated.Results: BDP-SSMs were successfully prepared with a content uniformity and reproducibility suitable for pulmonary administration. The maximum solubility of BDP in SSMs was approximately 1300 times its actual solubility. The particle size and zeta potential of BDP-SSMs were 19.89 ± 0.67 nm and -28.03 ± 2.05 mV, respectively. The SSMs system slowed down the release of BDP and all of the aerodynamic values of the aerosolized rehydrated BDP-SSMs were not only acceptable but indicated a significant level of deposition in the lungs.Conclusion: The SSM system might be an effective way of improving the therapeutic index of nebulized, poorly soluble corticosteroids

  14. Effect of cellular phospholipid modification on phorbol diester binding

    International Nuclear Information System (INIS)

    The influence of cellular lipid composition on the specific binding of [20-3H]phorbol-12,13-dibutyrate to intact human promyelocytic leukemia cells was investigated. Cellular phospholipid composition could be manipulated by culturing cells in serum-free, chemically defined media containing base analogues of phospholipid polar head groups. Human promyelocytic leukemia cells grown in the presence of dimethylethanolamine, monomethylethanolamine, 3-aminopropanol, or isopropylethanolamine assimilated these natural and unnatural base moieties into endogenous phospholipids to the extent that 22 to 52% of the cell glycerophospholipids contained the base analogue. The formation of the phospholipid analogues was accompanied by a pronounced reduction in the levels of intracellular choline and ethanolamine glycerophospholipids. Analogue-supplemented cultures exhibited a reduced growth rate compared to control cells maintained in choline-containing medium. Specific [20-3H ]phorbol-12,13-dibutyrate binding was examined in lipid-altered cells and shown to be markedly higher (approximately 200% of control) in cells grown with dimethyl- or monomethylethanolamine. In contrast, exposure of cells to 3-aminopropanol or isopropylethanolamine resulted in a major reduction in [20-3H]phorbol-12,13-dibutyrate binding. Only minimal changes in nonspecific binding occurred between control and experimental cells. Because phorbol esters are highly membrane targeted, it is possible that phospholipid modification or the resulting changes in membrane organization influence receptor dynamics

  15. Control of phospholipid flip-flop by transmembrane peptides

    Energy Technology Data Exchange (ETDEWEB)

    Kaihara, Masanori; Nakao, Hiroyuki; Yokoyama, Hirokazu [Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501 (Japan); Endo, Hitoshi [Quantum Beam Science Directorate, Japan Atomic Energy Agency, Tokai, Ibaraki 319-1195 (Japan); Ishihama, Yasushi [Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501 (Japan); Handa, Tetsurou [Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, 3500-3 Minami-Tamagaki-cho, Suzuka, Mie 513-8670 (Japan); Nakano, Minoru, E-mail: mnakano@pha.u-toyama.ac.jp [Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194 (Japan)

    2013-06-20

    Highlights: ► Phospholipid flip-flop in transmembrane peptide-containing vesicles was investigated. ► Peptides that contained polar residues in the center of the transmembrane region promoted phospholipid flip-flop. ► A bioinformatics approach revealed the presence of polar residues in the transmembrane region of ER membrane proteins. ► Polar residues in ER membrane proteins possibly provide flippase-like activity. - Abstract: We designed three types of transmembrane model peptides whose sequence originates from a frequently used model peptide KALP23, and we investigated their effects on phospholipid flip-flop. Time-resolved small-angle neutron scattering and a dithionite fluorescent quenching assay demonstrated that TMP-L, which has a fully hydrophobic transmembrane region, did not enhance phospholipid flip-flop, whereas TMP-K and TMP-E, which have Lys and Glu, respectively, in the center of their transmembrane regions, enhanced phospholipid flip-flop. Introduction of polar residues in the membrane-spanning helices is considered to produce a locally polar region and enable the lipid head group to interact with the polar side-chain inside the bilayers, thereby reducing the activation energy for the flip-flop. A bioinformatics approach revealed that acidic and basic residues account for 4.5% of the central region of the transmembrane domain in human ER membrane proteins. Therefore, polar residues in ER membrane proteins are considered to provide flippase-like activity.

  16. Decrease in membrane phospholipid unsaturation induces unfolded protein response.

    Science.gov (United States)

    Ariyama, Hiroyuki; Kono, Nozomu; Matsuda, Shinji; Inoue, Takao; Arai, Hiroyuki

    2010-07-16

    Various kinds of fatty acids are distributed in membrane phospholipids in mammalian cells and tissues. The degree of fatty acid unsaturation in membrane phospholipids affects many membrane-associated functions and can be influenced by diet and by altered activities of lipid-metabolizing enzymes such as fatty acid desaturases. However, little is known about how mammalian cells respond to changes in phospholipid fatty acid composition. In this study we showed that stearoyl-CoA desaturase 1 (SCD1) knockdown increased the amount of saturated fatty acids and decreased that of monounsaturated fatty acids in phospholipids without affecting the amount or the composition of free fatty acid and induced unfolded protein response (UPR), evidenced by increased expression of C/EBP homologous protein (CHOP) and glucose-regulated protein 78 (GRP78) mRNAs and splicing of Xbox-binding protein 1 (XBP1) mRNA. SCD1 knockdown-induced UPR was rescued by various unsaturated fatty acids and was enhanced by saturated fatty acid. Lysophosphatidylcholine acyltransferase 3 (LPCAT3), which incorporates preferentially polyunsaturated fatty acids into phosphatidylcholine, was up-regulated in SCD1 knockdown cells. Knockdown of LPCAT3 synergistically enhanced UPR with SCD1 knockdown. Finally we showed that palmitic acid-induced UPR was significantly enhanced by LPCAT3 knockdown as well as SCD1 knockdown. These results suggest that a decrease in membrane phospholipid unsaturation induces UPR.

  17. Control of phospholipid flip-flop by transmembrane peptides

    International Nuclear Information System (INIS)

    Highlights: ► Phospholipid flip-flop in transmembrane peptide-containing vesicles was investigated. ► Peptides that contained polar residues in the center of the transmembrane region promoted phospholipid flip-flop. ► A bioinformatics approach revealed the presence of polar residues in the transmembrane region of ER membrane proteins. ► Polar residues in ER membrane proteins possibly provide flippase-like activity. - Abstract: We designed three types of transmembrane model peptides whose sequence originates from a frequently used model peptide KALP23, and we investigated their effects on phospholipid flip-flop. Time-resolved small-angle neutron scattering and a dithionite fluorescent quenching assay demonstrated that TMP-L, which has a fully hydrophobic transmembrane region, did not enhance phospholipid flip-flop, whereas TMP-K and TMP-E, which have Lys and Glu, respectively, in the center of their transmembrane regions, enhanced phospholipid flip-flop. Introduction of polar residues in the membrane-spanning helices is considered to produce a locally polar region and enable the lipid head group to interact with the polar side-chain inside the bilayers, thereby reducing the activation energy for the flip-flop. A bioinformatics approach revealed that acidic and basic residues account for 4.5% of the central region of the transmembrane domain in human ER membrane proteins. Therefore, polar residues in ER membrane proteins are considered to provide flippase-like activity

  18. Characterization of a soluble, catalytically active form of Escherichia coli leader peptidase: requirement of detergent or phospholipid for optimal activity.

    Science.gov (United States)

    Tschantz, W R; Paetzel, M; Cao, G; Suciu, D; Inouye, M; Dalbey, R E

    1995-03-28

    Leader peptidase is a novel serine protease in Escherichia coli, which functions to cleave leader sequences from exported proteins. Its catalytic domain extends into the periplasmic space and is anchored to the membrane by two transmembrane segments located at the N-terminal end of the protein. At present, there is no information on the structure of the catalytic domain. Here, we report on the properties of a soluble form of leader peptidase (delta 2-75), and we compare its properties to those of the wild-type enzyme. We find that the truncated leader peptidase has a kcat of 3.0 S-1 and a Km of 32 microM with a pro-OmpA nuclease A substrate. In contrast to the wild-type enzyme (pI of 6.8), delta 2-75 is water-soluble and has an acidic isoelectric point of 5.6. We also show with delta 2-75 that the replacement of serine 90 and lysine 145 with alanine residues results in a 500-fold reduction in activity, providing further evidence that leader peptidase employs a catalytic serine/lysine dyad. Finally, we find that the catalysis of delta 2-75 is accelerated by the presence of the detergent Triton X-100, regardless if the substrate is pro-OmpA nuclease A or a peptide substrate. Triton X-100 is required for optimal activity of delta 2-75 at a level far below the critical micelle concentration. Moreover, we find that E. coli phospholipids stimulate the activity of delta 2-75, suggesting that phospholipids may play an important physiological role in the catalytic mechanism of leader peptidase. PMID:7696258

  19. Casein polymorphism heterogeneity influences casein micelle size in milk of individual cows.

    Science.gov (United States)

    Day, L; Williams, R P W; Otter, D; Augustin, M A

    2015-06-01

    Milk samples from individual cows producing small (148-155 nm) or large (177-222 nm) casein micelles were selected to investigate the relationship between the individual casein proteins, specifically κ- and β-casein phenotypes, and casein micelle size. Only κ-casein AA and β-casein A1A1, A1A2 and A2A2 phenotypes were found in the large casein micelle group. Among the small micelle group, both κ-casein and β-casein phenotypes were more diverse. κ-Casein AB was the dominant phenotype, and 3 combinations (AA, AB, and BB) were present in the small casein micelle group. A considerable mix of β-casein phenotypes was found, including B and I variants, which were only found in the small casein micelle group. The relative amount of κ-casein to total casein was significantly higher in the small micelle group, and the nonglycosylated and glycosylated κ-casein contents were higher in the milks with small casein micelles (primarily with κ-casein AB and BB variants) compared with the large micelle group. The ratio of glycosylated to nonglycosylated κ-casein was higher in the milks with small casein micelles compared with the milks with large casein micelles. This suggests that although the amount of κ-casein (both glycosylated and nonglycosylated) is associated with micelle size, an increased proportion of glycosylated κ-casein could be a more important and favorable factor for small micelle size. This suggests that the increased spatial requirement due to addition of the glycosyl group with increasing extent of glycosylation of κ-casein is one mechanism that controls casein micelle assembly and growth. In addition, increased electrostatic repulsion due to the sialyl residues on the glycosyl group could be a contributory factor. PMID:25828659

  20. Products and mechanism of the reaction of ozone with phospholipids in unilamellar phospholipid vesicles

    Energy Technology Data Exchange (ETDEWEB)

    Santrock, J.; Gorski, R.A.; O' Gara, J.F. (Biomedical Science Department, General Motors Research Laboratories, Warren, MI (United States))

    1992-01-01

    While considerable effort has been expended on determining the health effects of exposure to typical urban concentrations of O3, little is known about the chemical events responsible for toxicity. Phospholipids containing unsaturated fatty acids in the cell membranes of lung cells are likely reaction sites for inhaled ozone (O3). In this study, we examined the reaction of O3 with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) in unilamellar phospholipid vesicles. Reaction of ozone with the carbon-carbon double bond of POPC yielded an aldehyde and a hydroxy hydroperoxide. The hydroxy hydroperoxide eliminated H2O2 to yield a second aldehyde. Upon further ozonolysis, the aldehydes were oxidized to the corresponding carboxylic acids. A material balance showed that no other reaction consumed POPC and O3 or produced these products. As a mechanistic probe, we measured incorporation of oxygen-18 from 18O3 into aldehyde, carboxylic acid, and H2O2. Approximately 50% of the aldehyde oxygen atoms were derived from O3. Oxygen in H2O2 was derived solely from O3, where both oxygen atoms in a molecule of H2O2 were from the same molecule of O3. One of the carboxylic acid oxygen atoms was derived from the precursor aldehyde, while the other was derived from O3. These results support the following mechanism. Cleavage of the carbon-carbon double bond of POPC by O3 yields a carbonyl oxide and an aldehyde. Reaction of H2O with the carbonyl oxide yields a hydroxy hydroperoxide, preventing formation ozonide by reaction of the carbonyl oxide and aldehyde. Elimination of H2O2 from the hydroxy hydroperoxide yields a second aldehyde. Oxidation of the aldehydes by O3 yields carboxylic acids.

  1. [Tracheal phospholipid composition and respiratory distress syndrome of the newborn].

    Science.gov (United States)

    Obladen, M

    1979-03-01

    Tracheal or pharyngeal aspirates were collected in 50 newborn infants with and without respiratory distress syndrome (RDS). After lipid extraction the phospholipids were analyzed with 2-dimensional thin layer chromatography. Surface-active are lecithin (PC), phosphatidylglycerol (PG), and phosphatidylinositol (PI). Newborn infants with RDS always have a complete lack of PG, which makes up to 11% of phospholipid-phosphors in mature newborns. In all infants with and without RDS, a sharp increase of PC occurs in the lung effluent after birth. The recovery from RDS is characterized by marked changes of PI: this phospholipid rises up to twice its initial value if the infants survive. The PI-increase parallels the clinical improvement and reaches its maximum usually on the 5th day of life. At the time of the PI-peak, the infants' surfactant function is sufficient to maintain alveolar stability with spontaneous breathing. In infants dying from RDS the PI-increase was not observed.

  2. Neutron diffraction studies of amphipathic helices in phospholipid bilayers

    International Nuclear Information System (INIS)

    The structural feature which is thought to facilitate the interaction of many peptides with phospholipid bilayers is the ability to fold into an amphipathic helix. In most cases the exact location and orientation of this helix with respect to the membrane is not known, and may vary with factors such as pH and phospholipid content of the bilayer. The growing interest in this area is stimulated by indications that similar interactions can contribute to the binding of certain hormones to their cell-surface receptors. We have been using the techniques of neutron diffraction from stacked phospholipid bilayers in an attempt to investigate this phenomenon with a number of membrane-active peptides. Here we report some of our findings with three of these: the bee venom melittin; the hormone calcitonin; and a synthetic peptide representing the ion channel fragment of influenza A M2 protein

  3. Shear-induced morphology in mixed phospholipid films

    Science.gov (United States)

    Hirsa, Amir; Young, James; Posada, David; Lopez, Juan

    2014-11-01

    Flow of mixed phospholipid films on liquid surfaces plays a significant role in biological processes ranging from lipid bilayer fluidity and the associated behavior of cellular membranes, to flow on the liquid lining in the lungs. Phospholipid films are also central to the process of two-dimensional protein crystallization below a ligand-bearing film. Here, we study a binary mixture of phospholipids that form an insoluble monolayer on the air-water interface. Brewster angle microscopy reveals that a shearing flow induces a phase separation in the binary film, resulting in the appearance of 10 micron-scale dark domains. Hydrodynamic response of the binary film is quantified at the macro-scale by measurements of the surface shear viscosity, via a deep-channel surface viscometer. Reynolds number was shown to be a state variable, along with surface pressure, controlling the surface shear viscosity of a biotinylated lipid film.

  4. Neutron diffraction studies of amphipathic helices in phospholipid bilayers

    Energy Technology Data Exchange (ETDEWEB)

    Bradshaw, J.P.; Gilchrist, P.J. [Univ. of Edinburgh (United Kingdom); Duff, K.C. [Univ. of Edinburgh Medical School (United Kingdom); Saxena, A.M. [Brookhaven National Laboratory, Upton, NY (United States)

    1994-12-31

    The structural feature which is thought to facilitate the interaction of many peptides with phospholipid bilayers is the ability to fold into an amphipathic helix. In most cases the exact location and orientation of this helix with respect to the membrane is not known, and may vary with factors such as pH and phospholipid content of the bilayer. The growing interest in this area is stimulated by indications that similar interactions can contribute to the binding of certain hormones to their cell-surface receptors. We have been using the techniques of neutron diffraction from stacked phospholipid bilayers in an attempt to investigate this phenomenon with a number of membrane-active peptides. Here we report some of our findings with three of these: the bee venom melittin; the hormone calcitonin; and a synthetic peptide representing the ion channel fragment of influenza A M2 protein.

  5. Role of inositol phospholipid signaling in natural killer cell biology

    Directory of Open Access Journals (Sweden)

    Matthew eGumbleton

    2013-03-01

    Full Text Available Natural Killer (NK cells are important in the host defense against malignancy and infection. At a cellular level NK cells are activated when signals from activating receptors exceed signaling from inhibitory receptors. At a molecular level NK cells undergo an education process to prevent autoimmunity. Mouse models have shown important roles for inositol phospholipid signaling in lymphocytes. NK cells from mice with deletion in different members of the PI3K signaling pathway have defective development, natural killer cell repertoire expression (NKRR and effector function. Here we review the role of inositol phospholipid signaling in NK cell biology.

  6. Structure and mechanism of ATP-dependent phospholipid transporters

    DEFF Research Database (Denmark)

    Lopez Marques, Rosa Laura; Poulsen, Lisbeth Rosager; Bailly, Aurélien;

    2015-01-01

    Background ATP-binding cassette (ABC) transporters and P4-ATPases are two large and seemingly unrelated families of primary active pumps involved in moving phospholipids from one leaflet of a biological membrane to the other. Scope of review This review aims to identify common mechanistic features...... in the way phospholipid flipping is carried out by two evolutionarily unrelated families of transporters. Major conclusions Both protein families hydrolyze ATP, although they employ different mechanisms to use it, and have a comparable size with twelve transmembrane segments in the functional unit...

  7. Genetic Analysis of Digestive Physiology Using Fluorescent Phospholipid Reporters

    Science.gov (United States)

    Farber, Steven A.; Pack, Michael; Ho, Shiu-Ying; Johnson, Iain D.; Wagner, Daniel S.; Dosch, Roland; Mullins, Mary C.; Hendrickson, H. Stewart; Hendrickson, Elizabeth K.; Halpern, Marnie E.

    2001-05-01

    Zebrafish are a valuable model for mammalian lipid metabolism; larvae process lipids similarly through the intestine and hepatobiliary system and respond to drugs that block cholesterol synthesis in humans. After ingestion of fluorescently quenched phospholipids, endogenous lipase activity and rapid transport of cleavage products results in intense gall bladder fluorescence. Genetic screening identifies zebrafish mutants, such as fat free, that show normal digestive organ morphology but severely reduced phospholipid and cholesterol processing. Thus, fluorescent lipids provide a sensitive readout of lipid metabolism and are a powerful tool for identifying genes that mediate vertebrate digestive physiology.

  8. Targeted transferrin-modified polymeric micelles: enhanced efficacy in vitro and in vivo in ovarian carcinoma.

    Science.gov (United States)

    Sawant, Rupa R; Jhaveri, Aditi M; Koshkaryev, Alexander; Zhu, Lin; Qureshi, Farooq; Torchilin, Vladimir P

    2014-02-01

    In this study, transferrin (Tf)-modified poly(ethylene glycol)-phosphatidylethanolamine (mPEG-PE) micelles loaded with the poorly water-soluble drug, R547 (a potent and selective ATP-competitive cyclin-dependent kinase (CDK) inhibitor), were prepared and evaluated for their targeting efficiency and cytotoxicity in vitro and in vivo to A2780 ovarian carcinoma cells, which overexpress transferrin receptors (TfR). At 10 mM lipid concentration, both Tf-modified and plain micelles solubilized 800 μg of R547. Tf-modified micelles showed enhanced interaction with A2780 ovarian carcinoma cells in vitro. The involvement of TfR in endocytosis of Tf-modified micelles was confirmed by colocalization studies of micelle-treated cells with the endosomal marker Tf-Alexa488. We confirmed endocytosis of micelles in an intact form with micelles loaded with a fluorescent dye and additionally labeled with fluorescent lipid. The in vitro cytotoxicity and in vivo tumor growth inhibition studies in A2780-tumor bearing mice confirmed the enhanced efficacy of Tf-modified R547-loaded micelles compared to free drug solution and to nonmodified micelles. The results of this study demonstrate the potential application of Tf-conjugated polymeric micelles in the treatment of tumors overexpressing TfR. PMID:24325630

  9. Mesoscale Simulations and Experimental Studies of pH-Sensitive Micelles for Controlled Drug Delivery.

    Science.gov (United States)

    Wang, Yan; Li, Qiu Yu; Liu, Xu Bo; Zhang, Can Yang; Wu, Zhi Min; Guo, Xin Dong

    2015-11-25

    The microstructures of doxorubicin-loaded micelles prepared from block polymers His(x)Lys10 (x = 0, 5, 10) conjugated with docosahexaenoic acid (DHA) are investigated under different pH conditions, using dissipative particle dynamics (DPD) simulations. The conformation of micelles and the DOX distributions in micelles were obviously influenced by pH values and the length of the histidine segment. At pH >6.0, the micelles self-assembled from the polymers were dense and compact. The drugs were entrapped well within the micellar core. The particle size increases as the histidine length increases. With the decrease of pH value to be lower than 6.0, there was no distinct difference for the micelles self-assembled from the polymer without histidine residues. However, the micelles prepared from the polymers with histidine residues shows a structural transformation from dense to swollen conformation, leading to an increased particle size from 10.3 to 14.5 DPD units for DHD-His10Lys10 micelles. This structural transformation of micelles can accelerate the DOX release from micelles under lower pH conditions. The in vitro drug release from micelles is accelerated by the decrease of pH value from 7.4 (physiological environment) to 5.0 (lysosomal environment). The integration of simulation and experiments might be a valuable method for the optimization and design of biomaterials for drug delivery with desired properties. PMID:26539742

  10. Lowering of plasma phospholipid transfer protein activity by acute hyperglycaemia-induced hyperinsulinaemia in healthy men

    NARCIS (Netherlands)

    vanTol, A; Ligtenberg, JJM; Riemens, SC; vanHaeften, TW; Dullaart, RPF

    1997-01-01

    Human plasma contains two lipid transfer proteins involved in the remodelling of plasma lipoproteins: cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP). CETP mediates the transfer/exchange of cholesterylesters, triglycerides and phospholipids between high-density lip

  11. Phosphatidate Kinase, A Novel Enzyme in Phospholipid Metabolism (Characterization of the Enzyme from Suspension-Cultured Catharanthus roseus Cells).

    Science.gov (United States)

    Wissing, J. B.; Kornak, B.; Funke, A.; Riedel, B.

    1994-01-01

    Phosphatidate kinase (adenosine 5[prime]-triphosphate:phosphatidic acid phosphotransferase), a novel enzyme of phospholipid metabolism, was detected recently in the plasma membranes of suspension-cultured Catharanthus roseus cells and purified (J.B. Wissing, H. Behrbohm [1993] Plant Physiol 102: 1243-1249). In the present work the properties of phosphatidate kinase are described. The enzyme showed a pH optimum of 6.1 and an isoelectric point of 4.8, and was rather stable in the presence of its substrates. Although the kinase accepted both ATP and GTP, with Km values of about 12 and 18 [mu]M, respectively, the only lipid substrate was phosphatidic acid; neither lysophosphatidic acid nor any other lipid tested was phosphorylated. With 32P- and 14C-labeled diacylglycerol pyrophosphate, the product of the enzyme, it was shown that the kinase catalyzes a reversible reaction. The activity of the extracted enzyme depended on the presence of surfactants such as Triton X-100 or [beta]-octylglucoside, whereas deoxycholate was strongly inhibitory. Kinetic analysis with Triton X-100/phosphatidate mixed micelles performed according to the "surface dilution" kinetic model showed saturation kinetics with respect to both bulk and surface concentration of phosphatidate. The interfacial Michaelis constant for phosphatidate was determined as 0.6 mol %. PMID:12232252

  12. Effects of cholesterol or gramicidin on slow and fast motions of phospholipids in oriented bilayers.

    OpenAIRE

    Peng, Z. Y.; Simplaceanu, V; Dowd, S R; Ho, C.

    1989-01-01

    Nuclear spin-lattice relaxation both in the rotating frame and in the laboratory frame is used to investigate the slow and fast molecular motions of phospholipids in oriented bilayers in the liquid crystalline phase. The bilayers are prepared from a perdeuterated phospholipid labeled with a pair of 19F atoms at the 7 position of the 2-sn acyl chain. Phospholipid-cholesterol or phospholipid-gramicidin interactions are characterized by measuring the relaxation rates as a function of the bilayer...

  13. Estimation of interfacial acidity of sodium dodecyl sulfate micelles

    Indian Academy of Sciences (India)

    Arghya Dey; G Naresh Patwari

    2011-11-01

    An enhancement in the excited state proton transfer (ESPT) processes of coumarin-102 (C-102) dye was observed upon addition of salicylic acid and hydrochloric acid in sodium dodecyl sulfate (SDS) micellar solution. The phenomenon was observed only in the micellar medium of anionic surfactant SDS and not in case of cationic (CTAB) or neutral (Trition X -100) surfactants. ESPT of C-102 was also observed in aqueous solutions but on addition of very high concentrations of hydrochloric acid. However, on comparing the ratio of the protonated species from the emission spectra in the presence and absence of SDS micelle, a conclusive estimation of the local proton concentration at the Stern layer of SDS micelles could be evaluated.

  14. Silver chloride micelle-induced tuning of pseudocapacitive manganese dioxide

    International Nuclear Information System (INIS)

    Ag-doped pseudocapacitive MnO2 materials are synthesized by reacting MnO4− with Mn2+ solution intentionally tuned with AgCl micelles. AgCl micelles serve as inducing template and play dual role for MnO2 growth: porosity generator and Ag-doping agent. The AgCl micelle–induced MnO2 has higher porosity, higher specific surface area, higher electrical conductivity and better ion diffusion, thus exhibiting dramatically improved pseduocapacitance and charge-discharge performance. Compared with pure MnO2, the prepared MnO2 containing 5 atomic percent of Ag exhibits almost doubled specific capacitance (488F g−1) and the existence of Ag dopant in MnO2 enhances the charge-discharge efficiency

  15. Coverage and disruption of phospholipid membranes by oxide nanoparticles

    NARCIS (Netherlands)

    Pera, H.; Nolte, T.M.; Leermakers, F.A.M.; Kleijn, J.M.

    2014-01-01

    We studied the interactions of silica and titanium dioxide nanoparticles with phospholipid membranes and show how electrostatics plays an important role. For this, we systematically varied the charge density of both the membranes by changing their lipid composition and the oxide particles by changin

  16. Dynamic phospholipid signaling by G protein-coupled receptors

    NARCIS (Netherlands)

    Weernink, Paschal A. Oude; Han, Li; Jakobs, Karl H.; Schmidt, Martina

    2007-01-01

    G protein-coupled receptors (GPCRs) control a variety of fundamental cellular processes by regulating phospholipid signaling pathways. Essential for signaling by a large number of receptors is the hydrolysis of the membrane phosphoinositide PIP2 by phospholipase C (PLC) into the second messengers IP

  17. Prostaglandin phospholipid conjugates with unusual biophysical and cytotoxic properties

    DEFF Research Database (Denmark)

    Pedersen, Palle Jacob; Adolph, Sidsel K.; Andresen, Thomas Lars;

    2010-01-01

    in an aqueous buffer and both phospholipids are hydrolyzed by phospholipase A(2), but with different conversion rates and extent of hydrolysis. The cytotoxicity was evaluated in HT-29 and Colo205 cells and the conjugates induced cell death in the presence of phospholipase A(2) and surprisingly also...

  18. Membrane Phospholipid Redistribution in Cytokinesis: A Theoretical Model

    Institute of Scientific and Technical Information of China (English)

    Mei-Wen AN; Wen-Zhou WU; Wei-Yi CHEN

    2005-01-01

    In cell mitosis, cytokinesis is a major deformation process, during which the site of the contractile ring is determined by the biochemical stimulus from asters of the mitotic apparatus, actin and myosin assembly is related to the motion of membrane phospholipids, and local distribution and arrangement of the microfilament cytoskeleton are different at different cytokinesis stages. Based on the Zinemanas-Nir model, a new model is proposed in this study to simulate the entire process by coupling the biochemical stimulus with the mechanical actions. There were three assumptions in this model: the movements of phospholipid proteins are driven by gradients of biochemical stimulus on the membrane surface; the local assembly of actin and myosin filament depends on the amount of phospholipid proteins at the same location;and the surface tension includes membrane tensions due to both the passive deformation of the membrane and the active contraction of actin filament, which is determined by microfilament redistribution and rearrangement. This model could explain the dynamic movement of microfilaments during cytokinesis and predict cell deformation. The calculated results from this model demonstrated that the reorientation of phospholipid proteins and the redistribution and reorientation of microfilaments may play a crucial role in cell division. This model may better represent the cytokinesis process by the introduction of biochemical stimulus.

  19. PHOSPHOLIPIDS OF FIVE PSEUDOMONAD ARCHETYPES FOR DIFFERENT TOLUENE DEGRADATION PATHWAYS

    Science.gov (United States)

    Liquid chromatography/electrospray ionization/mass spectrometry (LC/ESI/MS) was used to determine phospholipid profiles for five reference pseudomonad strains harboring distinct toluene catabolic pathways: Pseudomonas putida mt-2, Pseudomonas putida F1, Burkholderia cepacia G4, B...

  20. Pairing of cholesterol with oxidized phospholipid species in lipid bilayers

    DEFF Research Database (Denmark)

    Khandelia, Himanshu; Loubet, Bastien; Olzynska, Agnieszka;

    2014-01-01

    . The additivity of the packing parameters of cholesterol and PZPC explains their cohabitation in a planar bilayer. Oxidized lipids are ubiquitously present in significant amounts in high- and low-density lipoprotein (HDL and LDL) particles, diseased tissues, and in model phospholipid mixtures containing...

  1. Biomembrane modeling: molecular dynamics simulation of phospholipid monolayers

    Energy Technology Data Exchange (ETDEWEB)

    Thompson, T.R.

    1979-01-01

    As a first step toward a computer model of a biomembrane-like bilayer, a dynamic, deterministric model of a phospholipid monolayer has been constructed. The model moves phospholipid-like centers of force according to an integrated law of motion in finite difference form. Forces on each phospholipid analogue are derived from the gradient of the local potential, itself the sum of Coulombic and short-range terms. The Coulombic term is approximated by use of a finite-difference form of Poisson's equation, while the short-range term results from finite-radius, pairwise summation of a Lennard-Jones potential. Boundary potentials are treated in such a way that the model is effectively infinite in extent in the plane of the monolayer. The two-dimensional virial theorem is used to find the surface pressure of the monolayer as a function of molecular area. Pressure-versus-area curves for simulated monolayers are compared to those of real monolayers. Dependence of the simulator's behavior on Lennard-Jones parameters and the specific geometry of the molecular analogue is discussed. Implications for the physical theory of phospholipid monolayers and bilayers are developed.

  2. Phospholipid signaling responses in salt-stressed rice leaves

    NARCIS (Netherlands)

    E. Darwish; C. Testerink; M. Khalil; O. El-Shihy; T. Munnik

    2009-01-01

    Salinity is one of the major environmental factors limiting growth and productivity of rice plants. In this study, the effect of salt stress on phospholipid signaling responses in rice leaves was investigated. Leaf cuts were radiolabeled with 32 P-orthophosphate and the lipids extracted and analyzed

  3. Advances in studies of phospholipids as carriers in skin topical application

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective:This article provides an overview of characteristics of phospholipids,the characteristics and influential factors of liposome and microemulsion as carriers for skin delivery of drugs,and the latest advances of the phospholipids carriers in transdermal delivery systems.The perspective is that phospholipids carriers may be capable of a wide range of applications in the transdermal defivery system.

  4. Stability of Self-Assembled Polymeric Micelles in Serum

    OpenAIRE

    Lu, Jiao; Owen, Shawn C.; Shoichet, Molly S.

    2011-01-01

    The stability of polymeric nanoparticles in serum is critical to their use in drug delivery where dilution after intravenous injection often results in nanoparticle disassembly and drug unloading; however, few investigate this in biologically relevant media. To gain greater insight into nanoparticle stability in blood, the stability of self-assembled polymeric micelles of poly(d,l-lactide-co-2-methyl-2-carboxytrimethylene carbonate)-g-poly(ethylene glycol), P(LA-co-TMCC)-g-PEG, were tested in...

  5. Neural modeling of bromelain extraction by reversed micelles

    OpenAIRE

    Ana Maria Frattini Fileti; Gilvan Anderson Fischer; Elias Basile Tambourgi

    2010-01-01

    A pulsed-cap microcolumn was used for bromelain extraction from pineapple juice by reversed micelles. The cationic micellar solution used BDBAC as the surfactant, isooctane as the solvent and hexanol as the co-solvent. In order to capture the dynamic behavior and the nonlinearities of the column, the operating conditions were modified in accordance with the central composite design for the experiment, using the ratio between the light phase flow rate and the total flow rate, and the time inte...

  6. Design and characterization of multicompartment micelles in aqueous solution

    OpenAIRE

    Kubowicz, Stephan

    2005-01-01

    Self-assembly of polymeric building blocks is a powerful tool for the design of novel materials and structures that combine different properties and may respond to external stimuli. In the past decades, most studies were focused on the self-assembly of amphiphilic diblock copolymers in solution. The dissolution of these block copolymers in a solvent selective for one block results mostly in the formation of micelles. The micellar structure of diblock copolymers is inherently limited to a homo...

  7. Polymer Micelles with Crystalline Cores for Thermally Triggered Release

    OpenAIRE

    Glover, Amanda L.; Nikles, Sarah M.; Nikles, Jacqueline A.; Brazel, Christopher S.; David E. Nikles

    2012-01-01

    Interest in the use of poly(ethylene glycol)-b-polycaprolactone diblock copolymers in a targeted, magnetically triggered drug delivery system has led to this study of the phase behavior of the polycaprolactone core. Four different diblock copolymers were prepared by the ring opening polymerization of caprolactone from the alcohol terminus of poly(ethylene glycol) monomethylether, Mn ~ 2,000. The critical micelle concentration depended on the degree of polymerization for the polycaprolactone b...

  8. Polymeric micelles for solubilization and targeting of hydrophobic drugs

    OpenAIRE

    Miller, Tobias

    2013-01-01

    This thesis focussed on the encapsulation of hydrophobic drugs into polymeric micelles and was intended to show the strengths and limitations of these self-assembling systems in terms of solubilization and drug targeting. Characterization of hydrophobic drug solubilization prior to intravenous injection was one of the key goals of this thesis. For this purpose a novel drug loading procedure was developed based on mechanistic considerations during the loading processes (Chapter 2). The cosolve...

  9. Biosensors with reversed micelle-enzyme sensitive membrane

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The effect of reversed micelle on the conformation of enzyme was studied by sensor techniques. By means of measurement of the response current of GOD enzyme membrane electrode, the effects of enzyme embedded in AOT reversed micellar on GOD conformation and catalytic activity are discussed. The results show that the response current increased greatly with decreasing ratio of GOD/AOT, meaning that the catalytic activity and the conformation stability of enzyme were enhanced.

  10. Construction of the Active Site of Metalloenzyme on Au NC Micelles

    Institute of Scientific and Technical Information of China (English)

    ZHANG, Zhiming; FU, Qiuan; HUANG, Xin; XU, Jiayun; LIU, Junqiu; SHEN, Jiacong

    2009-01-01

    For developing an efficient nanoenzyme system with self-assembly strategy, gold nanocrystal micelles (Au NC micelles) with inserted catalytic Zn(Ⅱ) centers were constructed by self-assembly of a catalytic ligand [N,N-bis(2-aminoethyl)-N'dodecylethylenediamine] Zn(Ⅱ) complexes (Zn(Ⅱ)L) on the surface of Au NC via hy- drophobic interaction. The functionalized Au NC micelles acted as an excellent nanoenzyme model for imitating ribonuclease. The catalytic capability of the Au NC micelles was evaluated by accelerating the cleavage of 2-hydroxypropyl p-nitrophenyl phosphate (HPNP). These functionalized Au NC micelles exhibited considerable ri- bonuclease-like activities by a factor of 4.9×104 (kcat/kuncat) for the cleavage of HPNP in comparison to the sponta- neous cleavage of HPNP at 37℃. The catalytic capability of the functionalized Au NC micelles can be considera- bly compared to other models reported previously as nanoenzymes under the comparable conditions.

  11. Permeability of phospholipid membrane for small polar molecules determined from osmotic swelling of giant phospholipid vesicles

    CERN Document Server

    Peterlin, Primoz; Diamant, Haim; Haleva, Emir

    2012-01-01

    A method for determining permeability of phospholipid bilayer based on the osmotic swelling of micrometer-sized giant unilamellar vesicles (GUVs) is presented as an alternative to the two established techniques, dynamic light scattering on liposome suspension, and electrical measurements on planar lipid bilayers. In the described technique, an individual GUV is transferred using a micropipette from a sucrose/glucose solution into an isomolar solution containing the solute under investigation. Throughout the experiment, vesicle cross-section is monitored and recorded using a digital camera mounted on a phase-contrast microscope. Using a least-squares procedure for circle fitting, vesicle radius R is computed from the recorded images of vesicle cross-section. Two methods for determining membrane permeability from the obtained R(t) dependence are described: the first one uses the slope of R(t) for a spherical GUV, and the second one the R(t) dependence around the transition point at which a flaccid vesicle trans...

  12. Light-responsive viscoelastic fluids based on anionic wormlike micelles.

    Science.gov (United States)

    Lu, Yechang; Zhou, Tengfei; Fan, Qing; Dong, Jinfeng; Li, Xuefeng

    2013-12-15

    A new class of light-responsive viscoelastic fluids based on anionic wormlike micelles is reported. The key components are sodium oleate (NaOA) and a cationic azobenzene dye, 1-[2-(4-phenylazo-phenoxy)-ethyl]-3-methylimidazolium bromide (C0AZOC2IMB). These binary systems are gel-like fluids at certain concentration ratios of [C0AZOC2IMB]/[NaOA], e.g. 35/100, owing to the formation of long, entangled wormlike micelles. The viscosity of these fluids can be controlled reversibly by light due to photo isomerization between trans-C0AZOC2IMB and cis-C0AZOC2IMB. For example, the zero-shear viscosity (η0) of an originally gel-like sample is high up to ~1300 Pa s when C0AZOC2IMB is in its trans from, whereas the mixture becomes a Newtonian fluid with η0 about 0.01 Pa s after UV light irradiation. For the post-irradiated cis-C0AZOC2IMB, short cylindrical micelles form, hence accounting for the lower viscosity. Evidence for the structural transition is provided by UV-vis spectra, rheology, (1)H NMR and cryo-transmission electronic microscopy measurements. PMID:24144381

  13. Hydrotropy: monomer-micelle equilibrium and minimum hydrotrope concentration.

    Science.gov (United States)

    Shimizu, Seishi; Matubayasi, Nobuyuki

    2014-09-01

    Drug molecules with low aqueous solubility can be solubilized by a class of cosolvents, known as hydrotropes. Their action has often been explained by an analogy with micelle formation, which exhibits critical micelle concentration (CMC). Indeed, hydrotropes also exhibit "minimum hydrotrope concentration" (MHC), a threshold concentration for solubilization. However, MHC is observed even for nonaggregating monomeric hydrotropes (such as urea); this raises questions over the validity of this analogy. Here we clarify the effect of micellization on hydrotropy, as well as the origin of MHC when micellization is not accompanied. On the basis of the rigorous Kirkwood-Buff (KB) theory of solutions, we show that (i) micellar hydrotropy is explained also from preferential drug-hydrotrope interaction; (ii) yet micelle formation reduces solubilization effeciency per hydrotrope molecule; (iii) MHC is caused by hydrotrope-hydrotrope self-association induced by the solute (drug) molecule; and (iv) MHC is prevented by hydrotrope self-aggregation in the bulk solution. We thus need a departure from the traditional view; the structure of hydrotrope-water mixture around the drug molecule, not the structure of the aqueous hydrotrope solutions in the bulk phase, is the true key toward understanding the origin of MHC.

  14. Predicting proton titration in cationic micelle and bilayer environments

    Energy Technology Data Exchange (ETDEWEB)

    Morrow, Brian H.; Shen, Jana K. [Department of Pharmaceutical Sciences, University of Maryland, Baltimore, Maryland 21201 (United States); Eike, David M.; Murch, Bruce P.; Koenig, Peter H. [Computational Chemistry, Modeling and Simulation GCO, Procter and Gamble, Cincinnati, Ohio 45201 (United States)

    2014-08-28

    Knowledge of the protonation behavior of pH-sensitive molecules in micelles and bilayers has significant implications in consumer product development and biomedical applications. However, the calculation of pK{sub a}’s in such environments proves challenging using traditional structure-based calculations. Here we apply all-atom constant pH molecular dynamics with explicit ions and titratable water to calculate the pK{sub a} of a fatty acid molecule in a micelle of dodecyl trimethylammonium chloride and liquid as well as gel-phase bilayers of diethyl ester dimethylammonium chloride. Interestingly, the pK{sub a} of the fatty acid in the gel bilayer is 5.4, 0.4 units lower than that in the analogous liquid bilayer or micelle, despite the fact that the protonated carboxylic group is significantly more desolvated in the gel bilayer. This work illustrates the capability of all-atom constant pH molecular dynamics in capturing the delicate balance in the free energies of desolvation and Coulombic interactions. It also shows the importance of the explicit treatment of ions in sampling the protonation states. The ability to model dynamics of pH-responsive substrates in a bilayer environment is useful for improving fabric care products as well as our understanding of the side effects of anti-inflammatory drugs.

  15. Predicting proton titration in cationic micelle and bilayer environments

    International Nuclear Information System (INIS)

    Knowledge of the protonation behavior of pH-sensitive molecules in micelles and bilayers has significant implications in consumer product development and biomedical applications. However, the calculation of pKa’s in such environments proves challenging using traditional structure-based calculations. Here we apply all-atom constant pH molecular dynamics with explicit ions and titratable water to calculate the pKa of a fatty acid molecule in a micelle of dodecyl trimethylammonium chloride and liquid as well as gel-phase bilayers of diethyl ester dimethylammonium chloride. Interestingly, the pKa of the fatty acid in the gel bilayer is 5.4, 0.4 units lower than that in the analogous liquid bilayer or micelle, despite the fact that the protonated carboxylic group is significantly more desolvated in the gel bilayer. This work illustrates the capability of all-atom constant pH molecular dynamics in capturing the delicate balance in the free energies of desolvation and Coulombic interactions. It also shows the importance of the explicit treatment of ions in sampling the protonation states. The ability to model dynamics of pH-responsive substrates in a bilayer environment is useful for improving fabric care products as well as our understanding of the side effects of anti-inflammatory drugs

  16. Binding of Diphtheria Toxin to Phospholipids in Liposomes

    Science.gov (United States)

    Alving, Carl R.; Iglewski, Barbara H.; Urban, Katharine A.; Moss, Joel; Richards, Roberta L.; Sadoff, Jerald C.

    1980-04-01

    Diphtheria toxin bound to the phosphate portion of some, but not all, phospholipids in liposomes. Liposomes consisting of dimyristoyl phosphatidylcholine and cholesterol did not bind toxin. Addition of 20 mol% (compared to dimyristoyl phosphatidylcholine) of dipalmitoyl phosphatidic acid, dicetyl phosphate, phosphatidylinositol phosphate, cardiolipin, or phosphatidylserine in the liposomes resulted in substantial binding of toxin. Inclusion of phosphatidylinositol in dimyristol phosphatidylcholine / cholesterol liposomes did not result in toxin binding. The calcium salt of dipalmitoyl phosphatidic acid was more effective than the sodium salt, and the highest level of binding occurred with liposomes consisting only of dipalmitoyl phosphatidic acid (calcium salt) and cholesterol. Binding of toxin to liposomes was dependent on pH, and the pattern of pH dependence varied with liposomes having different compositions. Incubation of diphtheria toxin with liposomes containing dicetyl phosphate resulted in maximal binding at pH 3.6, whereas binding to liposomes containing phosphatidylinositol phosphate was maximal above pH 7. Toxin did not bind to liposomes containing 20 mol% of a free fatty acid (palmitic acid) or a sulfated lipid (3-sulfogalactosylceramide). Toxin binding to dicetyl phosphate or phosphatidylinositol phosphate was inhibited by UTP, ATP, phosphocholine, or p-nitrophenyl phosphate, but not by uracil. We conclude that (a) diphtheria toxin binds specifically to the phosphate portion of certain phospholipids, (b) binding to phospholipids in liposomes is dependent on pH, but is not due only to electrostatic interaction, and (c) binding may be strongly influenced by the composition of adjacent phospholipids that do not bind toxin. We propose that a minor membrane phospholipid (such as phosphatidylinositol phosphate or phosphatidic acid), or that some other phosphorylated membrane molecule (such as a phosphoprotein) may be important in the initial binding of

  17. Surface tension model for surfactant solutions at the critical micelle concentration

    OpenAIRE

    Burlatsky, S. F.; Atrazhev, V. V.; Dmitriev, D. V.; Sultanov, V. I.; Timokhina, E. N.; Ugolkova, E. A.; Tulyani, S.; Vincitore, A.

    2013-01-01

    A model for the limiting surface tension of surfactant solutions (surface tension at and above the critical micelle concentration, cmc) was developed. This model takes advantage of the equilibrium between the surfactant molecules on the liquid/vacuum surface and in micelles in the bulk at the cmc. An approximate analytical equation for the surface tension at the cmc was obtained. The derived equation contains two parameters, which characterize the intermolecular interactions in the micelles, ...

  18. Microwave-assisted Palladium-micelle-catalyzed Suzuki Cross-coupling Reaction in Water

    Institute of Scientific and Technical Information of China (English)

    LIN Li; LI Sheng-hai; JIANG Ri-hua

    2011-01-01

    A microwave-accelerated Suzuki coupling procedure was developed via guanidinium ionic liquids(GILs)stabilized Pd-micelle.The Pd micelle/GILs play a key role in enhancing the activity,due to the highly dispersed Pd active sites and the phase transfer function of GILs,which ensures the adsorption of reactants and facilitates the translation of the intermediates to the surface of the micelle.

  19. Micelle swelling agent derived cavities for increasing hydrophobic organic compound removal efficiency by mesoporous micelle@silica hybrid materials

    KAUST Repository

    Shi, Yifeng

    2012-06-01

    Mesoporous micelle@silica hybrid materials with 2D hexagonal mesostructures were synthesized as reusable sorbents for hydrophobic organic compounds (HOCs) removal by a facile one-step aqueous solution synthesis using 3-(trimethoxysily)propyl-octadecyldimethyl-ammonium chloride (TPODAC) as a structure directing agent. The mesopores were generated by adding micelle swelling agent, 1,3,5-trimethyl benzene, during the synthesis and removing it afterward, which was demonstrated to greatly increase the HOC removal efficiency. In this material, TPODAC surfactant is directly anchored on the pore surface of mesoporous silica via SiOSi covalent bond after the synthesis due to its reactive Si(OCH 3) 3 head group, and thus makes the synthesized materials can be easily regenerated for reuse. The obtained materials show great potential in water treatment as pollutants sorbents. © 2011 Elsevier Inc. All rights reserved.

  20. Structure formation in binary mixtures of surfactants: vesicle opening-up to bicelles and octopus-like micelles

    Science.gov (United States)

    Noguchi, Hiroshi

    Micelle formation in binary mixtures of surfactants is studied using a coarse-grained molecular simulation. When a vesicle composed of lipid and detergent types of molecules is ruptured, a disk-shaped micelle, the bicelle, is typically formed. It is found that cup-shaped vesicles and bicelles connected with worm-like micelles are also formed depending on the surfactant ratio and critical micelle concentration. The obtained octopus shape of micelles agree with those observed in the cryo-TEM images reported in [S. Jain and F. S. Bates, Macromol. 37, 1511 (2004).]. Two types of connection structures between the worm-like micelles and the bicelles are revealed.

  1. Solubilization of docetaxel in poly(ethylene oxide)-block-poly(butylene/styrene oxide) micelles.

    Science.gov (United States)

    Elsabahy, Mahmoud; Perron, Marie-Eve; Bertrand, Nicolas; Yu, Ga-Er; Leroux, Jean-Christophe

    2007-07-01

    Poly(ethylene oxide)-block-poly(styrene oxide) (PEO-b-PSO) and PEO-b-poly(butylene oxide) (PEO-b-PBO) of different chain lengths were synthesized and characterized for their self-assembling properties in water by dynamic/static light scattering, spectrofluorimetry, and transmission electron microscopy. The resulting polymeric micelles were evaluated for their ability to solubilize and protect the anticancer drug docetaxel (DCTX) from degradation. The drug release kinetics as well as the cytotoxicity of the loaded micelles were assessed in vitro. All polymers formed micelles with a highly viscous core at low critical association concentrations (<10 mg/L). Micelle morphology depended on the nature of the hydrophobic block, with PBO- and PSO-based micelles yielding monodisperse spherical and cylindrical nanosized aggregates, respectively. The maximum solubilization capacity for DCTX ranged from 0.7 to 4.2% and was the highest for PSO micelles exhibiting the longest hydrophobic segment. Despite their high affinity for DCTX, PEO-b-PSO micelles were not able to efficiently protect DCTX against hydrolysis under accelerated stability testing conditions. Only PEO-b-PBO bearing 24 BO units afforded significant protection against degradation. In vitro, DCTX was released slower from the latter micelles, but all formulations possessed a similar cytotoxic effect against PC-3 prostate cancer cells. These data suggest that PEO-b-P(SO/BO) micelles could be used as alternatives to conventional surfactants for the solubilization of taxanes. PMID:17579476

  2. ADVANCES IN MICROEMULSION PHASE ON SELF-ASSEMBLY AND MICELLE EXTRACTION WITH BLOCK COPOLYMERS

    Institute of Scientific and Technical Information of China (English)

    Chen Guo; Hao Wen; Huizhou Liu

    2005-01-01

    In this paper we review our work on self-assembly of the system, poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) block copolymers, which is a kind of macromolecular complex fluids. The control of self-assembly could be obtained by adding inorganic salts or aliphatic alcohols. By self-assembly of amphiphilic block copolymers, a microemulsion phase is formed, which could be applied in micelle extraction, such as hollow-fiber membrane micelle extraction, magnetic micelle extraction and immobilized micelle extraction.

  3. Solution structure of detergent micelles at conditions relevant to membrane protein crystallization.

    Energy Technology Data Exchange (ETDEWEB)

    Littrell, K.; Thiyagarajan, P.; Tiede, D.; Urban, V.

    1999-07-02

    In this study small angle neutron scattering was used to characterize the formation of micelles in aqueous solutions of the detergents DMG and SPC as a function of detergent concentration and ionic strength of the solvent. The effects on the micelle structure of the additives glycerol and PEG, alone as well as in combination typical for actual membrane protein crystallization, were also explored. This research suggests that the micelles are cigar-like in form at the concentrations studied. The size of the micelles was observed to increase with increasing ionic strength but decrease with the addition of glycerol or PEG.

  4. Cholesterol-Enhanced Polylactide-Based Stereocomplex Micelle for Effective Delivery of Doxorubicin

    OpenAIRE

    Jixue Wang; Weiguo Xu; Jianxun Ding; Shengfan Lu; Xiaoqing Wang; Chunxi Wang; Xuesi Chen

    2015-01-01

    Nanoscale micelles as an effective drug delivery system have attracted increasing interest in malignancy therapy. The present study reported the construction of the cholesterol-enhanced doxorubicin (DOX)-loaded poly(D-lactide)-based micelle (CDM/DOX), poly(L-lactide)-based micelle (CLM/DOX), and stereocomplex micelle (CSCM/DOX) from the equimolar enantiomeric 4-armed poly(ethylene glycol)–polylactide copolymers in aqueous condition. Compared with CDM/DOX and CLM/DOX, CSCM/DOX showed the small...

  5. Atomistic Simulation of Solubilization of Polycyclic Aromatic Hydrocarbons in a Sodium Dodecyl Sulfate Micelle.

    Science.gov (United States)

    Liang, Xujun; Marchi, Massimo; Guo, Chuling; Dang, Zhi; Abel, Stéphane

    2016-04-19

    Solubilization of two polycyclic aromatic hydrocarbons (PAHs), naphthalene (NAP, 2-benzene-ring PAH) and pyrene (PYR, 4-benzene-ring PAH), into a sodium dodecyl sulfate (SDS) micelle was studied through all-atom molecular dynamics (MD) simulations. We find that NAP as well as PYR could move between the micelle shell and core regions, contributing to their distribution in both regions of the micelle at any PAH concentration. Moreover, both NAP and PYR prefer to stay in the micelle shell region, which may arise from the greater volume of the micelle shell, the formation of hydrogen bonds between NAP and water, and the larger molecular volume of PYR. The PAHs are able to form occasional clusters (from dimer to octamer) inside the micelle during the simulation time depending on the PAH concentration in the solubilization systems. Furthermore, the micelle properties (i.e., size, shape, micelle internal structure, alkyl chain conformation and orientation, and micelle internal dynamics) are found to be nearly unaffected by the solubilized PAHs, which is irrespective of the properties and concentrations of PAHs.

  6. Kinetic analysis of hydrogen production using anaerobic bacteria in reverse micelles

    Energy Technology Data Exchange (ETDEWEB)

    Zhi, Xiaohua; Yang, Haijun; Yuan, Zhuliang; Shen, Jianquan [Beijing National Laboratory for Molecular Sciences (BNLMS), Laboratory of New Materials, Institute of Chemistry, Chinese Academy of Sciences, Zhongguancun North First Street 2, Beijing 100190 (China)

    2010-04-15

    The micellar formation and entrapment of bacteria cell in reverse micelles were investigated by ultraviolet spectrum (UV), fluorescence spectrum, and scanning electron microscope (SEM). The hydrogen production in reverse micelles was confirmed. The Gompertz equation was employed to evaluate the hydrogen-producing behavior in reverse micellar systems. Different systems including dioctyl sulfosuccinate sodium salt (AOT)-isooctane, sodium dodecyl sulfate (SDS)-benzene and SDS-carbon tetrachloride (CCl{sub 4}) reverse micelles were analysized. The results revealed that the maximum rate of hydrogen production (R{sub m}) was also suitable to formulate the relationship between hydrogen-producing rate and hydrogen productivity in reverse micelles. (author)

  7. Near-Infrared Squaraine Dye Encapsulated Micelles for in Vivo Fluorescence and Photoacoustic Bimodal Imaging.

    Science.gov (United States)

    Sreejith, Sivaramapanicker; Joseph, James; Lin, Manjing; Menon, Nishanth Venugopal; Borah, Parijat; Ng, Hao Jun; Loong, Yun Xian; Kang, Yuejun; Yu, Sidney Wing-Kwong; Zhao, Yanli

    2015-06-23

    Combined near-infrared (NIR) fluorescence and photoacoustic imaging techniques present promising capabilities for noninvasive visualization of biological structures. Development of bimodal noninvasive optical imaging approaches by combining NIR fluorescence and photoacoustic tomography demands suitable NIR-active exogenous contrast agents. If the aggregation and photobleaching are prevented, squaraine dyes are ideal candidates for fluorescence and photoacoustic imaging. Herein, we report rational selection, preparation, and micelle encapsulation of an NIR-absorbing squaraine dye (D1) for in vivo fluorescence and photoacoustic bimodal imaging. D1 was encapsulated inside micelles constructed from a biocompatible nonionic surfactant (Pluoronic F-127) to obtain D1-encapsulated micelles (D1(micelle)) in aqueous conditions. The micelle encapsulation retains both the photophysical features and chemical stability of D1. D1(micelle) exhibits high photostability and low cytotoxicity in biological conditions. Unique properties of D1(micelle) in the NIR window of 800-900 nm enable the development of a squaraine-based exogenous contrast agent for fluorescence and photoacoustic bimodal imaging above 820 nm. In vivo imaging using D1(micelle), as demonstrated by fluorescence and photoacoustic tomography experiments in live mice, shows contrast-enhanced deep tissue imaging capability. The usage of D1(micelle) proven by preclinical experiments in rodents reveals its excellent applicability for NIR fluorescence and photoacoustic bimodal imaging.

  8. Rheological properties of novel viscoelastic micelle systems containing anionic-nonionic dimeric surfactant

    Institute of Scientific and Technical Information of China (English)

    方波; 曹丹红; 江体乾

    2008-01-01

    The viscoelastic micelle systems formed by novel anionic-nonionic dimeric surfactant and conventional cationic surfactant cetyltrimethylammonium(1631) were studied.The viscoelasticity,thixotropy,flow curves and constitutive equation for the novel viscoelastic micelle systems were investigated.The results show that the micelle systems possess viscoelasticity,thixotropy,and shear thinning property.Some micelle systems possess hysteresis loops showing both viscoelasticity and thixotropy.It is proved that the flow curves are characterized by the co-rotational Jeffreys constitutive equation correctly.

  9. Polyelectrolyte complex micelles by self-assembly of polypeptide-based triblock copolymer for doxorubicin delivery

    Directory of Open Access Journals (Sweden)

    Jeong Hwan Kim

    2014-08-01

    Full Text Available Polyelectrolyte complex micelles were prepared by self-assembly of polypeptide-based triblock copolymer as a new drug carrier for cancer chemotherapy. The triblock copolymer, poly(l-aspartic acid-b-poly(ethylene glycol-b-poly(l-aspartic acid (PLD-b-PEG-b-PLD, spontaneously self-assembled with doxorubicin (DOX via electrostatic interactions to form spherical micelles with a particle size of 60–80 nm (triblock ionomer complexes micelles, TBIC micelles. These micelles exhibited a high loading capacity of 70% (w/w at a drug/polymer ratio of 0.5 at pH 7.0. They showed pH-responsive release patterns, with higher release at acidic pH than at physiological pH. Furthermore, DOX-loaded TBIC micelles exerted less cytotoxicity than free DOX in the A-549 human lung cancer cell line. Confocal microscopy in A-549 cells indicated that DOX-loaded TBIC micelles were transported into lysosomes via endocytosis. These micelles possessed favorable pharmacokinetic characteristics and showed sustained DOX release in rats. Overall, these findings indicate that PLD-b-PEG-b-PLD polypeptide micelles are a promising approach for anti-cancer drug delivery.

  10. Quantification of fatty acids as methyl esters and phospholipids in cheese samples after separation of triacylglycerides and phospholipids

    Energy Technology Data Exchange (ETDEWEB)

    Hauff, Simone [University of Hohenheim, Institute of Food Chemistry, Garbenstrasse 28, D-70599 Stuttgart (Germany); Vetter, Walter [University of Hohenheim, Institute of Food Chemistry, Garbenstrasse 28, D-70599 Stuttgart (Germany)], E-mail: w-vetter@uni-hohenheim.de

    2009-03-23

    Determination of the individual fatty acid composition of neutral- and phospholipids as well as the phospholipid content of dairy food and other foodstuffs are important tasks in life sciences. For these purposes, a method was developed for the separation of lipids (standards of triolein and diacylphosphatidylcholines as well as three cheese samples) by solid-phase extraction using a self-packed column filled with partly deactivated silica. Non-halogenated solvents were used for the elution of the lipid classes. Cyclohexane/ethyl acetate (1:1, v/v) served for the elution of neutral lipids, while polar lipids were eluted with three solvents (ethyl acetate/methanol, methanol, and methanol/water) into one fraction. The separated lipid fractions were transesterified and the individual fatty acids were quantified by using gas chromatography coupled to electron ionization mass spectrometry (GC/EI-MS) in the selected ion monitoring (SIM) mode. The recovery rate for standard phosphatidylcholines was {approx}90% and cross-contamination from neutral lipids was negligible. The method was applied to cheese samples. Quantitative amounts of individual fatty acids in the phospholipid fraction were <0.002-0.29% of total lipids from camembert, <0.002-0.12% of total lipids from mozzarella, and <0.002-0.18% of total lipids in a goat cream cheese. Differences in the fatty acid pattern of neutral and polar lipids were detected. The quantity of the fatty acids determined in the phospholipid fraction was divided by the factor 0.7 in order to convert the fatty acid content into the phospholipid content of the cheese samples. This factor is based on the contribution of 16:0 to dipalmitoylphosphatidylcholine (DPPC). The resulting DPPC equivalents (DPPC{sub eq}) were found to be representative for the average contribution of fatty acids to all classes of phospholipids in dairy products. Using this approach, the phospholipid content of lipids from mozzarella, camembert, and goat cream cheese

  11. Doxorubicin-Loaded PEG-PCL-PEG Micelle Using Xenograft Model of Nude Mice: Effect of Multiple Administration of Micelle on the Suppression of Human Breast Cancer

    Directory of Open Access Journals (Sweden)

    Ming-Fa Hsieh

    2010-12-01

    Full Text Available The triblock copolymer is composed of two identical hydrophilic segments: Monomethoxy poly(ethylene glycol (mPEG and one hydrophobic segment poly(ε‑caprolactone (PCL; which is synthesized by coupling of mPEG-PCL-OH and mPEG‑COOH in a mild condition using dicyclohexylcarbodiimide and 4-dimethylamino pyridine. The amphiphilic block copolymer can self-assemble into nanoscopic micelles to accommodate doxorubixin (DOX in the hydrophobic core. The physicochemical properties and in vitro tests, including cytotoxicity of the micelles, have been characterized in our previous study. In this study, DOX was encapsulated into micelles with a drug loading content of 8.5%. Confocal microscopy indicated that DOX was internalized into the cytoplasm via endocystosis. A dose-finding scheme of the polymeric micelle (placebo showed a safe dose of PEG-PCL-PEG micelles was 71.4 mg/kg in mice. Importantly, the circulation time of DOX-loaded micelles in the plasma significantly increased compared to that of free DOX in rats. A biodistribution study displayed that plasma extravasation of DOX in liver and spleen occurred in the first four hours. Lastly, the tumor growth of human breast cancer cells in nude mice was suppressed by multiple injections (5 mg/kg, three times daily on day 0, 7 and 14 of DOX-loaded micelles as compared to multiple administrations of free DOX.

  12. Doxorubicin-Loaded PEG-PCL-PEG Micelle Using Xenograft Model of Nude Mice: Effect of Multiple Administration of Micelle on the Suppression of Human Breast Cancer

    International Nuclear Information System (INIS)

    The triblock copolymer is composed of two identical hydrophilic segments Monomethoxy poly(ethylene glycol) (mPEG) and one hydrophobic segment poly(ε-caprolactone) (PCL); which is synthesized by coupling of mPEG-PCL-OH and mPEG-COOH in a mild condition using dicyclohexylcarbodiimide and 4-dimethylamino pyridine. The amphiphilic block copolymer can self-assemble into nanoscopic micelles to accommodate doxorubixin (DOX) in the hydrophobic core. The physicochemical properties and in vitro tests, including cytotoxicity of the micelles, have been characterized in our previous study. In this study, DOX was encapsulated into micelles with a drug loading content of 8.5%. Confocal microscopy indicated that DOX was internalized into the cytoplasm via endocystosis. A dose-finding scheme of the polymeric micelle (placebo) showed a safe dose of PEG-PCL-PEG micelles was 71.4 mg/kg in mice. Importantly, the circulation time of DOX-loaded micelles in the plasma significantly increased compared to that of free DOX in rats. A biodistribution study displayed that plasma extravasation of DOX in liver and spleen occurred in the first four hours. Lastly, the tumor growth of human breast cancer cells in nude mice was suppressed by multiple injections (5 mg/kg, three times daily on day 0, 7 and 14) of DOX-loaded micelles as compared to multiple administrations of free DOX

  13. Doxorubicin-Loaded PEG-PCL-PEG Micelle Using Xenograft Model of Nude Mice: Effect of Multiple Administration of Micelle on the Suppression of Human Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Cuong, Nguyen-Van [Department of Biomedical Engineering, Chung Yuan Christian University, 200, Chung Pei Rd., Chung Li, Taiwan (China); Department of Chemical Engineering, Ho Chi Minh City University of Industry, 12 Nguyen Van Bao St, Ho Chi Minh (Viet Nam); Jiang, Jian-Lin; Li, Yu-Lun [Department of Biomedical Engineering, Chung Yuan Christian University, 200, Chung Pei Rd., Chung Li, Taiwan (China); Chen, Jim-Ray [Department of Pathology, Chang Gung Memorial Hospital at Keelung, Taiwan and Chang Gung University, College of Medicine, Taoyuan, Taiwan (China); Jwo, Shyh-Chuan [Division of General Surgery, Chang Gung Memorial Hospital at Keelung, Taiwan and Chang Gung University, College of Medicine, Taoyuan, Taiwan (China); Hsieh, Ming-Fa, E-mail: mfhsieh@cycu.edu.tw [Department of Biomedical Engineering, Chung Yuan Christian University, 200, Chung Pei Rd., Chung Li, Taiwan (China)

    2010-12-28

    The triblock copolymer is composed of two identical hydrophilic segments Monomethoxy poly(ethylene glycol) (mPEG) and one hydrophobic segment poly(ε-caprolactone) (PCL); which is synthesized by coupling of mPEG-PCL-OH and mPEG-COOH in a mild condition using dicyclohexylcarbodiimide and 4-dimethylamino pyridine. The amphiphilic block copolymer can self-assemble into nanoscopic micelles to accommodate doxorubixin (DOX) in the hydrophobic core. The physicochemical properties and in vitro tests, including cytotoxicity of the micelles, have been characterized in our previous study. In this study, DOX was encapsulated into micelles with a drug loading content of 8.5%. Confocal microscopy indicated that DOX was internalized into the cytoplasm via endocystosis. A dose-finding scheme of the polymeric micelle (placebo) showed a safe dose of PEG-PCL-PEG micelles was 71.4 mg/kg in mice. Importantly, the circulation time of DOX-loaded micelles in the plasma significantly increased compared to that of free DOX in rats. A biodistribution study displayed that plasma extravasation of DOX in liver and spleen occurred in the first four hours. Lastly, the tumor growth of human breast cancer cells in nude mice was suppressed by multiple injections (5 mg/kg, three times daily on day 0, 7 and 14) of DOX-loaded micelles as compared to multiple administrations of free DOX.

  14. Hybrid electrospun chitosan-phospholipids nanofibers for transdermal drug delivery

    DEFF Research Database (Denmark)

    Mendes, Ana Carina Loureiro; Gorzelanny, Christian; Halter, Natalia;

    2016-01-01

    Chitosan (Ch) polysaccharide was mixed with phospholipids (P) to generate electrospun hybrid nanofibers intended to be used as platforms for transdermal drug delivery. Ch/P nanofibers exibithed average diameters ranging from 248 +/- 94 nm to 600 +/- 201 nm, depending on the amount of phospholipids...... Saline (PBS) solution. Cytotoxicity studies (WST-1 and LDH assays) demonstrated that the hybrid nanofibers have suitable biocompatibility. Fluorescence microscopy, also suggested that L929 cells seeded on top of the CH/P hybrid have similar metabolic activity comparatively to the cells seeded on tissue...... culture plate (control). The release of curcumin, diclofenac and vitamin B12, as model drugs, from Ch/P hybrid nanofibers was investigated, demonstrating their potential utilization as a transdermal drug delivery system....

  15. Interactions Mode of Amphoteric Molecules with Ordered Phospholipid Membrane

    Institute of Scientific and Technical Information of China (English)

    SUNJin; CHENGGang; HEZhong-gui; WANGshu-jun; CHENJi-min

    2003-01-01

    Aim:To explore interaction mode between amphoteric molecules with the ordered phospholipid membrane.Methods:Membrane interactions were determined by immobilized artificial membrane(IAM) chromatography and solutes hydroph9obicity was measured by n-octanol/buffer system.Results:The ampholytes,similar to bases,generally exhibited higher membrane affinity than expected from their hydrophobicity,resulting from the attractive polar interaction with phospholipid membrane.Furthermore,the strength of additional polar interaction with membrane(Δlg kLAM) was then calculat ed.The Δlg KIAMvalues were far greater for bases and ampholytes ranging from 0.50-1.39,than those for acids and neutrals with the scope from-0.55-0.44.Conclusion :Considering the microspecies distribution of amphoteric molecules,it was assumed that not only neutral and positive but also zwitterionic microspecies are capable of partitioning into ordered amphoteric lipid membrane with complementarily conformational and energetically favorable interactions.

  16. Study on Phospholipid Composition of Erythrocyte Membrane in Hypophosphatemic Cows

    Institute of Scientific and Technical Information of China (English)

    SHI Fa-qing; XUAN Da-wei; XU Shi-Wen; WANG Zhen-yong

    2002-01-01

    The phospholipid constituents of the erythrocyte membrane of cows in hypophosophorus were detected with the field cases and the group comparison. The cows were divided into three groups: the hemoglobinuria group (HN), the hypophosphatemia group (HP) and the control group (CK). The content of the phospholipid constituent in HN and HP obviously changed: phosphatidylethaanolamine (PE) content in HN was significantly lower than that in HP and CK; but sphingomyline (SM) and phosphatidycholine (PC)+ phosphatidylserine (PS) content in HN were significantly higher than that in the two other groups; in comparison between HP and CK, PC + PS content was lower and SM content was higher in HP; significant positive correlation and negative correlation were observed between serum phosphorus and PE content, serum phosphorus and SM content respectively.

  17. Phospholipid interactions in model membrane systems. I. Experiments on monolayers.

    OpenAIRE

    Mingins, J; Stigter, D; Dill, K A

    1992-01-01

    We study the lateral headgroup interactions among phosphatidylcholine (PC) molecules and among phosphatidylethanolamine (PE) molecules in monolayers and extend our previous models. In this paper, we present an extensive set of pressure-area isotherms and surface potential experiments on monolayers of phospholipids ranging from 14 to 22 carbons in length at the n-heptane/water interface, over a wide range of temperature, salt concentration, and pH on the acid side. The pressure data presented ...

  18. Incorporation of peptides in phospholipid aggregates using ultrasound

    OpenAIRE

    Silva, Raquel; Little, Collin; Ferreira, Helena; Paulo, Artur Cavaco

    2008-01-01

    This study presents the highlights of ultrasonic effects on peptides incorporated on phospholipid aggregates (liposomes). These liposomes or vesicles are known as transport agents in skin drug delivery and for hair treatment. They might be a good model to deliver larger peptides into hair to restore fibre strength after hair coloration, modelling, permanent wave and/or straightening. The preparation of liposomes 1,2-dipalmitoyl-sn-glycerol-3-phosphocholine (DPPC) with peptides (LLLLK LLLLK LL...

  19. Role of inositol phospholipid signaling in natural killer cell biology

    OpenAIRE

    Gumbleton, Matthew; Kerr, William G.

    2013-01-01

    Natural killer (NK) cells are important for host defense against malignancy and infection. At a cellular level NK cells are activated when signals from activating receptors exceed signaling from inhibitory receptors. At a molecular level NK cells undergo an education process to both prevent autoimmunity and acquire lytic capacity. Mouse models have shown important roles for inositol phospholipid signaling in lymphocytes. NK cells from mice with deletion in different members of the inositol ph...

  20. Metformin Decouples Phospholipid Metabolism in Breast Cancer Cells

    OpenAIRE

    Smith, Tim A. D.; Phyu, Su M.

    2016-01-01

    Introduction The antidiabetic drug metformin, currently undergoing trials for cancer treatment, modulates lipid and glucose metabolism both crucial in phospholipid synthesis. Here the effect of treatment of breast tumour cells with metformin on phosphatidylcholine (PtdCho) metabolism which plays a key role in membrane synthesis and intracellular signalling has been examined. Methods MDA-MB-468, BT474 and SKBr3 breast cancer cell lines were treated with metformin and [3H-methyl]choline and [14...

  1. Effect of dipolar-angle on phospholipid assembly

    CERN Document Server

    Paul, Tanay

    2016-01-01

    We report the effect of lipid head-group dipole orientation on phase behaviour of phospholipid assembly. The work explains molecular-scale mechanism of ion-lipid, anesthetic-lipid interactions where reorientation of dipoles play important role in membrane potential modification. Molecular Dynamics simulations are performed to analyse structure-property relationship and dynamical behaviour of lipid biomembranes considering coarse-grained model interactions.

  2. Ultradeformable phospholipid vesicles as a drug delivery system: a review

    OpenAIRE

    Romero, Eder Lilia

    2015-01-01

    Maria Jose Morilla, Eder Lilia RomeroNanomedicine Research Program, Department of Science and Technology, National University of Quilmes, Buenos Aires, Argentina Abstract: Ultradeformable vesicles are highly deformable (elastic/flexible) liposomes made of phospholipids plus highly mobile hydrophilic detergents capable of penetrating the intact skin across the stratum corneum and reaching the viable epidermis. Ultradeformable vesicles are more effective than conventional liposomes in deliveri...

  3. Association of anti-phospholipid antibodies with connective tissue diseases

    OpenAIRE

    Reena Rai; Swetha, T.

    2015-01-01

    Background: The antiphospholipid antibodies (APLA) are directed against phospholipids and their binding proteins and are frequently found in association with connective tissue disorders. Systemic lupus erythematoses (SLE) with APLA may cause a diagnostic dilemma as there are several manifestations like haemolytic anemia, thrombocytopenia, neurologic manifestations, leg ulcerations, serositis proteinuria which overlap in both these conditions. We conducted a study to find out the association o...

  4. Phosphatidylinositol, a phospholipid of ice-nucleating bacteria.

    OpenAIRE

    Kozloff, L. M.; Turner, M.A.; Arellano, F; Lute, M

    1991-01-01

    The nature of the phospholipids of the various bacteria that have ice nucleation activity in supercooled water has been determined. The seven bacteria studied included Pseudomonas syringae, Erwinia herbicola, three Escherichia coli K-12 strains that are phenotypically Ice+ because they contain plasmids with different amounts of either P. syringae or E. herbicola cloned DNA, and two E. coli K-12 strains without cloned ice gene DNA. All five Ice+ bacterial strains contained small amounts (0.1 t...

  5. The Effects of Gramicidin on the Structure of Phospholipid Assemblies

    OpenAIRE

    Szule, J. A.; Rand, R. P.

    2003-01-01

    Gramicidin is an antibiotic peptide that can be incorporated into the monolayers of cell membranes. Dimerization through hydrogen bonding between gramicidin monomers in opposing leaflets of the membrane results in the formation of an iontophoretic channel. Surrounding phospholipids influence the gating properties of this channel. Conversely, gramicidin incorporation has been shown to affect the structure of spontaneously formed lipid assemblies. Using small-angle x-ray diffraction and model s...

  6. Penetration of surfactin into phospholipid monolayers: nanoscale interfacial organization.

    Science.gov (United States)

    Eeman, M; Berquand, A; Dufrêne, Y F; Paquot, M; Dufour, S; Deleu, M

    2006-12-19

    Atomic force microscopy (AFM) combined with surface pressure-area isotherms were used to probe the interfacial behavior of phospholipid monolayers following penetration of surfactin, a cyclic lipopeptide produced by Bacillus subtilis strains. Prior to penetration experiments, interfacial behavior of different surfactin molecules (cyclic surfactins with three different aliphatic chain lengths--S13, S14, and S15--and a linear surfactin obtained by chemical cleavage of the cycle of the surfactin S15) has been investigated. A more hydrophobic aliphatic chain induces greater surface-active properties of the lipopeptide. The opening of the peptide ring reduces the surface activity. The effect of phospholipid acyl chain length (dimyristoylphosphatidylcholine, dipalmitoylphosphatidylcholine- (DPPC), and distearoylphosphatidylcholine) and phospholipid polar head (DPPC, dipalmitoylphosphatidylethanolamine and dipalmitoylphosphatidylserine) on monolayer penetration properties of the surfactin S15 has been explored. Results showed that while the lipid monolayer thickness and the presence of electrostatic repulsions from the interfacial film do not significantly influence surfactin insertion, these parameters strongly modulate the ability of the surfactin to alter the nanoscale organization of the lipid films. We also probed the effect of surfactin structure (influence of the aliphatic chain length and of the cyclic structure of the peptide ring) on the behavior of DPPC monolayers. AFM images and isotherms showed that surfactin penetration is promoted by longer lipopeptide chain length and a cyclic polar head. This indicates that hydrophobic interactions are of main importance for the penetration power of surfactin molecules.

  7. Phospholipid and Respiratory Quinone Analyses From Extreme Environments

    Science.gov (United States)

    Pfiffner, S. M.

    2008-12-01

    Extreme environments on Earth have been chosen as surrogate sites to test methods and strategies for the deployment of space craft in the search for extraterrestrial life. Surrogate sites for many of the NASA astrobiology institutes include the South African gold mines, Canadian subpermafrost, Atacama Desert, and acid rock drainage. Soils, sediments, rock cores, fracture waters, biofilms, and service and drill waters represent the types of samples collected from these sites. These samples were analyzed by gas chromatography mass spectrometry for phospholipid fatty acid methyl esters and by high performance liquid chromatography atmospheric pressure chemical ionization tandem mass spectrometry for respiratory quinones. Phospholipid analyses provided estimates of biomass, community composition, and compositional changes related to nutritional limitations or exposure to toxic conditions. Similar to phospholipid analyses, respiratory quinone analyses afforded identification of certain types of microorganisms in the community based on respiration and offered clues to in situ redox conditions. Depending on the number of samples analyzed, selected multivariate statistical methods were applied to relate membrane lipid results with site biogeochemical parameters. Successful detection of life signatures and refinement of methodologies at surrogate sites on Earth will be critical for the recognition of extraterrestrial life. At this time, membrane lipid analyses provide useful information not easily obtained by other molecular techniques.

  8. Maternal Baicalin Treatment Increases Fetal Lung Surfactant Phospholipids in Rats

    Directory of Open Access Journals (Sweden)

    Chung-Ming Chen

    2011-01-01

    Full Text Available Baicalin is a flavonoid compound purified from the medicinal plant Scutellaria baicalensis Georgi and has been reported to stimulate surfactant protein (SP-A gene expression in human lung epithelial cell lines (H441. The aims of this study were to determine whether maternal baicalin treatment could increase lung surfactant production and induce lung maturation in fetal rats. This study was performed with timed pregnant Sprague-Dawley rats. One-day baicalin group mothers were injected intraperitoneally with baicalin (5 mg/kg/day on Day 18 of gestation. Two-day baicalin group mothers were injected intraperitoneally with baicalin (5 mg/kg/day on Days 17 and 18 of gestation. Control group mothers were injected with vehicle alone on Day 18 of gestation. On Day 19 of gestation, fetuses were delivered by cesarean section. Maternal treatment with 2-day baicalin significantly increased saturated phospholipid when compared with control group and total phospholipid in fetal lung tissue when compared with control and 1-day baicalin groups. Antenatal treatment with 2-day baicalin significantly increased maternal growth hormone when compared with control group. Fetal lung SP-A mRNA expression and maternal serum corticosterone levels were comparable among the three experimental groups. Maternal baicalin treatment increases pulmonary surfactant phospholipids of fetal rat lungs and the improvement was associated with increased maternal serum growth hormone. These results suggest that antenatal baicalin treatment might accelerate fetal rat lung maturation.

  9. The micromethod for determination of cholesterol, cholesteryl esters and phospholipids

    Directory of Open Access Journals (Sweden)

    Okabe,Akinobu

    1974-12-01

    Full Text Available We examined the method for determining microquantities of lipids, including cholesterol, cholesteryl esters and phospholipids. A standard colorimetric procedure of cholesteryl esters was modified to accommodate a quantitative thin-layer chromatography. This method involved the following steps. (1 Separation of lipids by a thin-layer chromatography: Lipids were applied to Silica gel G plates. Plates were developed with petroleum ether-diethyl etheracetic acid (82: 18: 2, vIvIv. (2 Elution of cholesterol and its esters from scraped silica gel: After scraping the silica gel with adhered cholesterol and its esters, they were eluted with chloroform-methanol (4: 1, v,tv. In the case of phspholipids, the silica gel was calcified. (3 Colorimetric determination of the lipids: Cholesterol and its esters eluted from the silica gel were determined by the method of ZAK with ROSENTHAL'S color reagent directly and after saponification, respectively. Phospholipids were calculated from the phosphorous content determined by the method of KATES. On the basis of examination of recovery and analyses of lipids extracted from tissue, it was concluded that this method permitted a reliable estimation of microquantities of cholesterol, its esters and phospholipids from small amounts of biological materials.

  10. Hybrid electrospun chitosan-phospholipids nanofibers for transdermal drug delivery.

    Science.gov (United States)

    Mendes, Ana C; Gorzelanny, Christian; Halter, Natalia; Schneider, Stefan W; Chronakis, Ioannis S

    2016-08-20

    Chitosan (Ch) polysaccharide was mixed with phospholipids (P) to generate electrospun hybrid nanofibers intended to be used as platforms for transdermal drug delivery. Ch/P nanofibers exibithed average diameters ranging from 248±94nm to 600±201nm, depending on the amount of phospholipids used. Fourier Transformed Infra-Red (FTIR) spectroscopy and Dynamic Light Scattering (DLS) data suggested the occurrence of electrostatic interactions between amine groups of chitosan with the phospholipid counterparts. The nanofibers were shown to be stable for at least 7days in Phosphate Buffer Saline (PBS) solution. Cytotoxicity studies (WST-1 and LDH assays) demonstrated that the hybrid nanofibers have suitable biocompatibility. Fluorescence microscopy, also suggested that L929 cells seeded on top of the CH/P hybrid have similar metabolic activity comparatively to the cells seeded on tissue culture plate (control). The release of curcumin, diclofenac and vitamin B12, as model drugs, from Ch/P hybrid nanofibers was investigated, demonstrating their potential utilization as a transdermal drug delivery system. PMID:27286632

  11. Changes in phospholipid metabolism during B lymphocyte activation

    International Nuclear Information System (INIS)

    Phospholipid metabolism in murine B lymphocytes stimulated with anti-Ig bound to Sepharose has been examined. T cell-depleted splenic B lymphocytes cultured with Sepharose-coupled, affinity-purified goat anti-mouse Ig (GAMIg) increased the incorporation of 32PO4 into phosphatidic acid and phosphatidylinositol within 3 hr and increased [3H]-thymidine uptake at 48 hr. No increase in labeling was observed in phosphatidylethanolamine, phosphatidylcholine, or phosphatidylserine. Based on both negative and positive selection procedures, it was demonstrated that these responses occurred in B lymphocytes. In contrast to the thymidine uptake response did not require the presence of accessory cells or exogenous cytokines. The same selective changes in phospholipid metabolism were observed in neoplastic B lymphocytes (BCL1) after treatment with Sepharose anti-μ, but not with Sepharose anti-Ia or Sepharose normal Ig. The dose-response relationships of 32PO4 incorporation into phosphatidic acid and phosphatidylinositol and [3H] thymidine uptake were nearly identical in BCL1 cells. The results of these experiments indicate that interaction B lymphocytes with insolubilized anti-Ig results in prompt and selective changes in phospholipid metabolism that appear to be correlated with B lymphocyte proliferation

  12. Preparation and evaluation of novel mixed micelles as nanocarriers for intravenous delivery of propofol

    Directory of Open Access Journals (Sweden)

    Li Xinru

    2011-01-01

    Full Text Available Abstract Novel mixed polymeric micelles formed from biocompatible polymers, poly(ethylene glycol-poly(lactide (mPEG-PLA and polyoxyethylene-660-12-hydroxy stearate (Solutol HS15, were fabricated and used as a nanocarrier for solubilizing poorly soluble anesthetic drug propofol. The solubilization of propofol by the mixed micelles was more efficient than those made of mPEG-PLA alone. Micelles with the optimized composition of mPEG-PLA/Solutol HS15/propofol = 10/1/5 by weight had particle size of about 101 nm with narrow distribution (polydispersity index of about 0.12. Stability analysis of the mixed micelles in bovine serum albumin (BSA solution indicated that the diblock copolymer mPEG efficiently protected the BSA adsorption on the mixed micelles because the hydrophobic groups of the copolymer were efficiently screened by mPEG, and propofol-loaded mixed micelles were stable upon storage for at least 6 months. The content of free propofol in the aqueous phase for mixed micelles was lower by 74% than that for the commercial lipid emulsion. No significant differences in times to unconsciousness and recovery of righting reflex were observed between mixed micelles and commercial lipid formulation. The pharmacological effect may serve as pharmaceutical nanocarriers with improved solubilization capacity for poorly soluble drugs.

  13. Cross-linked self-assembled micelle based nanosensor for intracellular pH measurements

    DEFF Research Database (Denmark)

    Ek, Pramod Kumar; Søndergaard, Rikke Vicki; Windschiegl, Barbara;

    2014-01-01

    formation. The copolymer, poly(ethylene glycol)-b-poly(2-aminoethyl methacrylate)-b-poly(styrene) (PEG-b-PAEMA-b-PS), was synthesized by isolated macroinitiator atom transfer radical polymerization that forms micelles spontaneously in water. The PAEMA shell of the micelle was hereafter cross...

  14. Effect of Spacers on CMCs and Micelle-forming Enthalpies of Gemini Surfactants by Titration Microcalorimetry

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The critical micelle concentrations (CMC) and the micelle-forming enthalpies (D Hmic) of gemini surfactants were first measured by the precise titration microcalorimetry. The results showed that D Hmic values are negative, and there is an exothermal minimum between s=4 and s=6. Furthermore, the CMCs of the surfactants are in good agreement with literature values.

  15. Histological study on side effects and tumor targeting of a block copolymer micelle on rats.

    Science.gov (United States)

    Kawaguchi, Takanori; Honda, Takashi; Nishihara, Masamichi; Yamamoto, Tatsuhiro; Yokoyama, Masayuki

    2009-06-19

    Histological examinations were performed with polymeric micelle-injected rats for evaluations of possible toxicities of polymeric micelle carriers. Weight of major organs as well as body weight of rats was measured after multiple intravenous injections of polymeric micelles forming from poly(ethylene glycol)-b-poly(aspartate) block copolymer. No pathological toxic side effects were observed at two different doses, followed only by activation of the mononuclear phagocyte system (MPS) in the spleen, liver, lung, bone marrow, and lymph node. This finding confirms the absence of--or the very low level of--in vivo toxicity of the polymeric micelle carriers that were reported in previous animal experiments and clinical results. Then, immunohistochemical analyses with a biotinylated polymeric micelle confirmed specific accumulation of the micelle in the MPS. The immunohistochemical analyses also revealed, first, very rapid and specific accumulation of the micelle in the vasculatures of tumor capsule of rat ascites hepatoma AH109A, and second, the micelle's scanty infiltration into tumor parenchyma. This finding suggests a unique tumor-accumulation mechanism that is very different from simple EPR effect-based tumor targeting.

  16. Pharmacokinetics and biodistribution of polymeric micelles of paclitaxel with Pluronic P123

    Institute of Scientific and Technical Information of China (English)

    Li-mei HAN; Lie GUO; Li-jun ZHANG; Qing-song WANG; Xiao-ling FANG

    2006-01-01

    Aim: To investigate the preparation, in vitro release, in vivo pharmacokinetics and tissue distribution of a novel polymeric micellar formulation of paclitaxel (PTX) with Pluronic P123. Methods: The polymeric micelles of paclitaxel with Pluronic PI23 were prepared by a solid dispersion method. The characteristics of micelles including particle size distribution, morphology and in vitro release of PTX from micelles were carried out. PTX-loaded micellar solutions were administered through the tail vein to healthy Sprague-Dawley rats and Kunming strain mice to assess the pharmacokinetics and tissue distribution of PTX, respectively. Taxol, the commercially available intravenous formulation of PTX, was also administered as control. Results: By using a dynamic light scattering sizer and a transmission electron microscopy, it was shown that the PTX-loaded micelles had a mean size of approximately 25 nm with narrow size distribution and a spherical shape. PTX was continuously released from Pluronic PI23 micelles in release medium containing 1 mol/L sodium salicylate for 24 h at 37℃. In the pharmacokinetic assessment, t1/2β and AUC of micelle formulation were 2.3 and 2.9-fold higher than that of Taxol injection. And the PTX-loaded micelles increased the uptake of PTX in the plasma, ovary and uterus, lung, and kidney, but decreased uptake in the liver and brain in the biodistribution study. Conclusion: Polymeric micelles using Pluronic P123 can effectively solubilize PTX, prolong blood circulation time and modify the biodistribution of PTX.

  17. Peptide-conjugated micelles as a targeting nanocarrier for gene delivery

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Wen Jen, E-mail: wjlin@ntu.edu.tw; Chien, Wei Hsuan [National Taiwan University, School of Pharmacy, Graduate Institute of Pharmaceutical Sciences (China)

    2015-09-15

    The aim of this study was to develop peptide-conjugated micelles possessing epidermal growth factor receptor (EGFR) targeting ability for gene delivery. A sequence-modified dodecylpeptide, GE11(2R), with enhancing EGF receptor binding affinity, was applied in this study as a targeting ligand. The active targeting micelles were composed of poly(d,l-lactide-co-glycolide)-poly(ethylene glycol) (PLGA-PEG) copolymer conjugated with GE11(2R)-peptide. The particle sizes of peptide-free and peptide-conjugated micelles were 277.0 ± 5.1 and 308.7 ± 14.5 nm, respectively. The peptide-conjugated micelles demonstrated the cellular uptake significantly higher than peptide-free micelles in EGFR high-expressed MDA-MB-231 and MDA-MB-468 cells due to GE11(2R)-peptide specificity. Furthermore, the peptide-conjugated micelles were able to encapsulate plasmid DNA and expressed cellular transfection higher than peptide-free micelles in EGFR high-expressed cells. The EGFR-targeting delivery micelles enhanced DNA internalized into cells and achieved higher cellular transfection in EGFR high-expressed cells.

  18. Tuneable & degradable polymeric micelles for drug delivery: from synthesis to feasibility in vivo

    NARCIS (Netherlands)

    Rijcken, C.J.F.

    2007-01-01

    In recent years, colloidal systems (e.g. liposomes, nanoparticles and micelles) are increasingly applied as vehicles for controlled drug delivery purposes. Ideally, the encapsulation of hydrophobic drugs in a micellar core prolongs the systemic circulation and drug-loaded micelles selectively accumu

  19. The Role of Decorated SDS Micelles in Sub-CMC Protein Denaturation and Association

    DEFF Research Database (Denmark)

    Andersen, Kell; Oliveira, Cristiano Luis Pinto De; Larsen, K.L.;

    2009-01-01

    . Our data provide key structural insights into decorated micelle complexes with proteins, revealing a remarkable diversity in the different conformations they can stabilize. The data highlight that a minimum decorated micelle size, which may be a key driving force for intermolecular protein association...

  20. Dithiol-PEG-PDLLA micelles: preparation and evaluation as potential topical ocular delivery vehicle.

    Science.gov (United States)

    Yang, Jian; Yan, Jing; Zhou, Zhihan; Amsden, Brian G

    2014-04-14

    Thiol-modified nanoparticles have potential applications in mucoadhesive drug delivery and have been examined in this regard for topical ocular delivery. In this paper we provide a simple method for the synthesis of a dithiol terminated amphiphilic diblock copolymer. Bidentate dithiol-poly(ethylene glycol)-poly(d,l-lactide) (SH2-PEG-PDLLA) was synthesized and micelles with dithiol-containing coronas were prepared from this block copolymer via the emulsion method. In vitro release studies indicated that the presence of the thiol groups at the surface did not affect the rate of release of dexamethasone, used as a representative ocular drug. The micelles also showed low cytotoxicity to human corneal epithelial cells (HCEC) and murine fibroblast cells (3T3 cells). A hydrophobic red fluorophore, Nile red, was loaded into the core of micelles and confocal microscopy was used to study HCEC uptake and retention of the micelles. The micelles were rapidly endocytosed by the HCEC, with intracellular micelle levels remaining unchanged with incubation times from 5 to 120 min. Interestingly, Nile red was eliminated significantly more slowly from HCECs treated with the thiolated micelles. These results suggest that these dithiolated micelles may be effective for topical ocular drug delivery. PMID:24611557

  1. Dissipative particle dynamics simulation study of poly(2-oxazoline)-based multicompartment micelle nanoreactor.

    Science.gov (United States)

    Chun, Byeong Jae; Fisher, Christina Clare; Jang, Seung Soon

    2016-02-17

    We investigate multicompartment micelles consisting of poly(2-oxazoline)-based triblock copolymers for nanoreactor applications, using the DPD simulation method to characterize the internal structure of the micelles and the distribution of reactant. The DPD simulation parameters are determined from the Flory-Huggins interaction parameter (χFH). From the snapshots of the micellar structures and radial distribution function of polymer blocks, it is clearly presented that the micelle is multicompartmental. In addition, by implementing the DPD simulations in the presence of reactants, it is found that Reac-C4 and Reac-OPh are associate well with the hydrophilic shell of the micelle, whereas the other two reactants, Reac-Ph and Reac-Cl, are not incorporated into the micelle. From our DPD simulations, we confirm that the miscibility (solubility) of reactant with the micelle has a strong correlation with the rate of hydrolysis kinetic resolution. Utilizing accurate methods evaluating accurate χFH parameters for molecular interactions in micelle system, this DPD simulation can have a great potential to predict the structures of micelles consisting of designed multiblock copolymers for useful reactions. PMID:26853511

  2. Determination of the aggregation number for micelles by isothermal titration calorimetry

    DEFF Research Database (Denmark)

    Olesen, Niels Erik; Holm, Rene; Westh, Peter

    2014-01-01

    Isothermal titration calorimetry (ITC) has previously been applied to estimate the aggregation number (n), Gibbs free energy (ΔG), enthalpy (ΔH) and entropy (ΔS) of micellization. However, some difficulties of micelle characterization by ITC still remain; most micelles have aggregation numbers...

  3. The association of low-molecular-weight hydrophobic compounds with native casein micelles in bovine milk.

    Science.gov (United States)

    Cheema, M; Mohan, M S; Campagna, S R; Jurat-Fuentes, J L; Harte, F M

    2015-08-01

    The agreed biological function of the casein micelles in milk is to carry minerals (calcium, magnesium, and phosphorus) from mother to young along with amino acids for growth and development. Recently, native and modified casein micelles were used as encapsulating and delivery agents for various hydrophobic low-molecular-weight probes. The ability of modified casein micelles to bind certain probes may derive from the binding affinity of native casein micelles. Hence, a study with milk from single cows was conducted to further elucidate the association of hydrophobic molecules into native casein micelles and further understand their biological function. Hydrophobic and hydrophilic extraction followed by ultraperformance liquid chromatography-high resolution mass spectrometry analysis were performed over protein fractions obtained from size exclusion fractionation of raw skim milk. Hydrophobic compounds, including phosphatidylcholine, lyso-phosphatidylcholine, phosphatidylethanolamine, and sphingomyelin, showed strong association exclusively to casein micelles as compared with whey proteins, whereas hydrophilic compounds did not display any preference for their association among milk proteins. Further analysis using liquid chromatography-tandem mass spectrometry detected 42 compounds associated solely with the casein-micelles fraction. Mass fragments in tandem mass spectrometry identified 4 of these compounds as phosphatidylcholine with fatty acid composition of 16:0/18:1, 14:0/16:0, 16:0/16:0, and 18:1/18:0. These results support that transporting low-molecular-weight hydrophobic molecules is also a biological function of the casein micelles in milk.

  4. Preparation and Characterization of Individual and Multi-drug Loaded Physically Entrapped Polymeric Micelles.

    Science.gov (United States)

    Rao, Deepa A; Nguyen, Duc X; Mishra, Gyan P; Doddapaneni, Bhuvana Shyam; Alani, Adam W G

    2015-01-01

    Amphiphilic block copolymers like polyethyleneglycol-block-polylactic acid (PEG-b-PLA) can self-assemble into micelles above their critical micellar concentration forming hydrophobic cores surrounded by hydrophilic shells in aqueous environments. The core of these micelles can be utilized to load hydrophobic, poorly water soluble drugs like docetaxel (DTX) and everolimus (EVR). Systematic characterization of the micelle structure and drug loading capabilities are important before in vitro and in vivo studies can be conducted. The goal of the protocol described herein is to provide the necessary characterization steps to achieve standardized micellar products. DTX and EVR have intrinsic solubilities of 1.9 and 9.6 µg/ml respectively Preparation of these micelles can be achieved through solvent casting which increases the aqueous solubility of DTX and EVR to 1.86 and 1.85 mg/ml, respectively. Drug stability in micelles evaluated at room temperature over 48 hr indicates that 97% or more of the drugs are retained in solution. Micelle size was assessed using dynamic light scattering and indicated that the size of these micelles was below 50 nm and depended on the molecular weight of the polymer. Drug release from the micelles was assessed using dialysis under sink conditions at pH 7.4 at 37 (o)C over 48 hr. Curve fitting results indicate that drug release is driven by a first order process indicating that it is diffusion driven. PMID:26382662

  5. Synchrotron Small-Angle X-ray Scattering Study of Cross-Linked Polymeric Micelles.

    Science.gov (United States)

    Kim, Hyun-Chul; Jin, Kyeong Sik; Lee, Se Guen; Kim, Eunjoo; Lee, Sung Jun; Jeong, Sang Won; Lee, Seung Woo; Kim, Kwang-Woo

    2016-06-01

    Polymeric micelles of methoxypoly(ethylene glycol)-b-poly(lactide) containing lysine units (mPEG-PLA-Lys4) were cross-linked by reacting of lysine moieties with a bifunctional bis(N-hydroxy-succinimide ester). The micelles were characterized in aqueous solution using dynamic light scattering, transmission electron microscopy, and synchrotron small-angle X-ray scattering. The mPEG-PLA-Lys4 was synthesized through the ring-opening polymerization of N6-carbobenzyloxy-L-lysine N-carboxyanhydride with amine-terminated mPEG-PLA and subsequent deprotection. The polymeric micelles showed enhanced micelle stability after cross-linking, which was confirmed by adding sodium dodecyl sulfate as a destabilizing agent. The average diameters measured via dynamic light scattering were 19.1 nm and 29.2 nm for non-cross-linked polymeric micelles (NCPMs) and cross-linked polymeric micelles (CPMs), respectively. The transmission electron microscopy images showed that the size of the polymeric micelles increased slightly due to cross-linking, which was in good agreement with the DLS measurements. The overall structures and internal structural changes of NCPMs and CPMs in aqueous solution were studied in detail using synchrotron X-ray scattering method. According to the structural parameters of X-ray scattering analysis, CPMs with a more densely packed core structure were formed by reacting bifunctional cross-linking agents with lysine amino groups located in the innermost core of the polymeric micelles. PMID:27427731

  6. Preparation and evaluation of novel mixed micelles as nanocarriers for intravenous delivery of propofol

    Science.gov (United States)

    Li, Xinru; Zhang, Yanhui; Fan, Yating; Zhou, Yanxia; Wang, Xiaoning; Fan, Chao; Liu, Yan; Zhang, Qiang

    2011-12-01

    Novel mixed polymeric micelles formed from biocompatible polymers, poly(ethylene glycol)-poly(lactide) (mPEG-PLA) and polyoxyethylene-660-12-hydroxy stearate (Solutol HS15), were fabricated and used as a nanocarrier for solubilizing poorly soluble anesthetic drug propofol. The solubilization of propofol by the mixed micelles was more efficient than those made of mPEG-PLA alone. Micelles with the optimized composition of mPEG-PLA/Solutol HS15/propofol = 10/1/5 by weight had particle size of about 101 nm with narrow distribution (polydispersity index of about 0.12). Stability analysis of the mixed micelles in bovine serum albumin (BSA) solution indicated that the diblock copolymer mPEG efficiently protected the BSA adsorption on the mixed micelles because the hydrophobic groups of the copolymer were efficiently screened by mPEG, and propofol-loaded mixed micelles were stable upon storage for at least 6 months. The content of free propofol in the aqueous phase for mixed micelles was lower by 74% than that for the commercial lipid emulsion. No significant differences in times to unconsciousness and recovery of righting reflex were observed between mixed micelles and commercial lipid formulation. The pharmacological effect may serve as pharmaceutical nanocarriers with improved solubilization capacity for poorly soluble drugs.

  7. Shaping and patterning gold nanoparticles via micelle templated photochemistry

    Science.gov (United States)

    Kundrat, F.; Baffou, G.; Polleux, J.

    2015-09-01

    Shaping and positioning noble metal nanostructures are essential processes that still require laborious and sophisticated techniques to fabricate functional plasmonic interfaces. The present study reports a simple photochemical approach compatible with micellar nanolithography and photolithography that enables the growth, arrangement and shaping of gold nanoparticles with tuneable plasmonic resonances on glass substrates. Ultraviolet illumination of surfaces coated with gold-loaded micelles leads to the formation of gold nanoparticles with micro/nanometric spatial resolution without requiring any photosensitizers or photoresists. Depending on the extra-micellar chemical environment and the illumination wavelength, block copolymer micelles act as reactive and light-responsive templates, which enable to grow gold deformed nanoparticles (potatoids) and nanorings. Optical characterization reveals that arrays of individual potatoids and rings feature a localized plasmon resonance around 600 and 800 nm, respectively, enhanced photothermal properties and high temperature sustainability, making them ideal platforms for future developments in nanochemistry and biomolecular manipulation controlled by near-infrared-induced heat.Shaping and positioning noble metal nanostructures are essential processes that still require laborious and sophisticated techniques to fabricate functional plasmonic interfaces. The present study reports a simple photochemical approach compatible with micellar nanolithography and photolithography that enables the growth, arrangement and shaping of gold nanoparticles with tuneable plasmonic resonances on glass substrates. Ultraviolet illumination of surfaces coated with gold-loaded micelles leads to the formation of gold nanoparticles with micro/nanometric spatial resolution without requiring any photosensitizers or photoresists. Depending on the extra-micellar chemical environment and the illumination wavelength, block copolymer micelles act as

  8. Structure and flexibility of worm-like micelles

    DEFF Research Database (Denmark)

    Jerke, G.; Pedersen, J.S.; Egelhaaf, S.U.;

    1997-01-01

    Small-angle neutron scattering and static light scattering experiments have been performed on worm-like micelles formed by soybean lecithin and trace amounts of water in deuterated iso-octane. The structure and flexibility of the aggregates have been investigated as a function of solution...... composition. The data analysis comprises an application from results of conformation space renormalization group theory and a non-linear least-squares fitting procedure based upon a recently developed numerical expression for the scattering function of a worm-like chain with excluded volume effects....

  9. Mechano-responsive hydrogels crosslinked by reactive block copolymer micelles

    Science.gov (United States)

    Xiao, Longxi

    Hydrogels are crosslinked polymeric networks that can swell in water without dissolution. Owing to their structural similarity to the native extracelluar matrices, hydrogels have been widely used in biomedical applications. Synthetic hydrogels have been designed to respond to various stimuli, but mechanical signals have not incorporated into hydrogel matrices. Because most tissues in the body are subjected to various types of mechanical forces, and cells within these tissues have sophisticated mechano-transduction machinery, this thesis is focused on developing hydrogel materials with built-in mechano-sensing mechanisms for use as tissue engineering scaffolds or drug release devices. Self-assembled block copolymer micelles (BCMs) with reactive handles were employed as the nanoscopic crosslinkers for the construction of covalently crosslinked networks. BCMs were assembled from amphiphilic diblock copolymers of poly(n-butyl acrylate) and poly(acrylic acid) partially modified with acrylate. Radical polymerization of acrylamide in the presence of micellar crosslinkers gave rise to elastomeric hydrogels whose mechanical properties can be tuned by varying the BCM composition and concentration. TEM imaging revealed that the covalently integrated BCMs underwent strain-dependent reversible deformation. A model hydrophobic drug, pyrene, loaded into the core of BCMs prior to the hydrogel formation, was dynamically released in response to externally applied mechanical forces, through force-induced reversible micelle deformation and the penetration of water molecules into the micelle core. The mechano-responsive hydrogel has been studied for tissue repair and regeneration purposes. Glycidyl methacrylate (GMA)-modified hyaluronic acid (HA) was photochemically crosslinked in the presence of dexamethasone (DEX)-loaded crosslinkable BCMs. The resultant HA gels (HAxBCM) contain covalently integrated micellar compartments with DEX being sequestered in the hydrophobic core. Compared

  10. Salicylic acid induces vanillin synthesis through the phospholipid signaling pathway in Capsicum chinense cell cultures

    OpenAIRE

    Rodas-Junco, Beatriz A; Cab-Guillen, Yahaira; Muñoz-Sanchez, J Armando; Vázquez-Flota, Felipe; Monforte-Gonzalez, Miriam; Hérnandez-Sotomayor, S M Teresa

    2013-01-01

    Signal transduction via phospholipids is mediated by phospholipases such as phospholipase C (PLC) and D (PLD), which catalyze hydrolysis of plasma membrane structural phospholipids. Phospholipid signaling is also involved in plant responses to phytohormones such as salicylic acid (SA). The relationships between phospholipid signaling, SA, and secondary metabolism are not fully understood. Using a Capsicum chinense cell suspension as a model, we evaluated whether phospholipid signaling modulat...

  11. Three-dimensional structure of the ion-channel forming peptide trichorzianin TA VII bound to sodium dodecyl sulfate micelles.

    Science.gov (United States)

    Condamine, E; Rebuffat, S; Prigent, Y; Ségalas, I; Bodo, B; Davoust, D

    1998-08-01

    Trichorzianin TA VII, Ac0 U1 A2 A3 U4 J5 Q6 U7 U8 U9 S10 L11 U12 P13 V14 U15 I16 Q17 Q18 Fol19, is a nonadecapeptide member of the peptaibol antibiotics biosynthesized by Trichoderma soil fungi, which is characterized by a high proportion of the alpha, alpha-dialkylated amino acids, alpha-aminoisobutyric acid (Aib, U) and isovaline (Iva, J), an acetylated N-terminus and a C-terminal phenylalaninol (Pheol, Fol). The main interest in such peptides stems from their ability to interact with phospholipid bilayers and form voltage-dependent transmembrane channels in planar lipid bilayers. In order to provide insights into the lipid-peptide interaction promoting the voltage gating, the conformational study of TA VII in the presence of perdeuterated sodium dodecyl sulfate (SDS-d25) micelles has been carried out. 1H sequential assignment have been performed with the use of two-dimensional homo- and -heteronuclear nmr techniques including double quantum filtered correlated spectroscopy, homonuclear Hartmann-Hahn, nuclear Overhauser effect spectroscopy, 1H-13C heteronuclear single quantum correlation, and heteronuclear multiple bond correlation. Conformational parameters, such as 3JNHC alpha H coupling constants, temperature coefficients of amide protons (delta gamma/delta TNH) and quantitative nuclear Overhauser enhancement data, lead to detailed structural information. Ninety-eight three-dimensional structures consistent with the nmr data were generated from 231 interproton distances six phi dihedral angle restraints, using restrained molecular dynamics and energy minimization calculations. The average rms deviation between the 98 refined structures and the energy-minimized average structure is 0.59 A for the backbone atoms. The structure of trichorzianin TA VII associated with SDS micelles, as determined by these methods, is characterized by two right-handed helical segments involving residues 1-8 and 11-19, linked by a beta-turn that leads to an angle about 90 degrees-100

  12. Effects of bile salts on percolation and size of AOT reversed micelles.

    Science.gov (United States)

    Yang, Hui; Erford, Karen; Kiserow, Douglas J; McGown, Linda B

    2003-06-15

    The effects of two trihydroxy bile salts, sodium taurocholate (NaTC) and 3-[(3-cholamidylpropyl)dimethylammonio]-1-propane sulfonate (CHAPS), on the size, shape and percolation temperature of reversed micelles formed by sodium bis(2-ethylhexyl)sulfosuccinate (AOT) in isooctane were studied. The percolation temperature of the reversed micelles decreased upon inclusion of bile salts, indicating increased water uptake. Dynamic light scattering (DLS) measurements showed consistent enlargement of reversed micelles upon addition of the bile salts; the hydrodynamic radius increased sixfold in the presence of 10 mM CHAPS and doubled in the presence of 5 mM NaTC. Inclusion of the enzyme yeast alcohol dehydrogenase (YADH) increased the percolation temperature and distorted the spherical structure of the AOT reversed micelles. The spherical structure was restored upon addition of bile salt. These results may help to explain the increase in activity of YADH in AOT reversed micelles upon addition of bile salts.

  13. Effective repair of traumatically injured spinal cord by nanoscale block copolymer micelles

    Science.gov (United States)

    Shi, Yunzhou; Kim, Sungwon; Huff, Terry B.; Borgens, Richard B.; Park, Kinam; Shi, Riyi; Cheng, Ji-Xin

    2010-01-01

    Spinal cord injury results in immediate disruption of neuronal membranes, followed by extensive secondary neurodegenerative processes. A key approach for repairing injured spinal cord is to seal the damaged membranes at an early stage. Here, we show that axonal membranes injured by compression can be effectively repaired using self-assembled monomethoxy poly(ethylene glycol)-poly(D,L-lactic acid) di-block copolymer micelles. Injured spinal tissue incubated with micelles (60 nm diameter) showed rapid restoration of compound action potential and reduced calcium influx into axons for micelle concentrations much lower than the concentrations of polyethylene glycol, a known sealing agent for early-stage spinal cord injury. Intravenously injected micelles effectively recovered locomotor function and reduced the volume and inflammatory response of the lesion in injured rats, without any adverse effects. Our results show that copolymer micelles can interrupt the spread of primary spinal cord injury damage with minimal toxicity.

  14. Process of forming compounds using reverse micelle or reverse microemulsion systems

    Science.gov (United States)

    Linehan, John C.; Fulton, John L.; Bean, Roger M.

    1998-01-01

    The present invention is directed to a process for producing a nanometer-sized metal compound. The process comprises forming a reverse micelle or reverse microemulsion system comprising a polar fluid in a non-polar or low-polarity fluid. A first reactant comprising a multi-component, water-soluble metal compound is introduced into the polar fluid in a non-polar or low-polarity fluid. This first reactant can be introduced into the reverse micelle or reverse microemulsion system during formation thereof or subsequent to the formation of the reverse micelle or microemulsion system. The water-soluble metal compound is then reacted in the reverse micelle or reverse microemulsion system to form the nanometer-sized metal compound. The nanometer-sized metal compound is then precipitated from the reverse micelle or reverse microemulsion system.

  15. Tumor homing indocyanine green encapsulated micelles for near infrared and photoacoustic imaging of tumors.

    Science.gov (United States)

    Uthaman, Saji; Bom, Joon-suk; Kim, Hyeon Sik; John, Johnson V; Bom, Hee-Seung; Kim, Seon-Jong; Min, Jung-Joon; Kim, Il; Park, In-Kyu

    2016-05-01

    Photoacoustic imaging (PAI) is an emerging analytical modality that is under intense preclinical development for the early diagnosis of various medical conditions, including cancer. However, the lack of specific tumor targeting by various contrast agents used in PAI obstructs its clinical applications. In this study, we developed indocyanine green (ICG)-encapsulated micelles specific for the CD 44 receptor and used in near infrared and photoacoustic imaging of tumors. ICG was hydrophobically modified prior to loading into hyaluronic acid (HA)-based micelles utilized for CD 44 based-targeting. We investigated the physicochemical characteristics of prepared HA only and ICG-encapsulated HA micelles (HA-ICG micelles). After intravenous injection of tumor-bearing mice, the bio-distribution and in vivo photoacoustic images of ICG-encapsulated HA micelles accumulating in tumors were also investigated. Our study further encourages the application of this HA-ICG-based nano-platform as a tumor-specific contrast agent for PAI.

  16. Synthesis of Cross-Linked Polymeric Micelle pH Nanosensors

    DEFF Research Database (Denmark)

    Ek, Pramod Kumar; Jølck, Rasmus Irming; Andresen, Thomas Lars

    2015-01-01

    at the micelle shell using CuAAC results in a stabilized micelle pH nanosensor. Compared to the postmicelle modification strategy, the mixed-micellization approach increases the control of the overall composition of the nanosensors.Both approaches provide stable nanosensors with similar pKa profiles and thereby......The design flexibility that polymeric micelles offer in the fabrication of optical nanosensors for ratiometric pH measurements is investigated. pH nanosensors based on polymeric micelles are synthesized either by a mixed-micellization approach or by a postmicelle modification strategy. In the mixed......-micellization approach, self-assembly of functionalized unimers followed by shell cross-linking by copper-catalyzed azide-alkyne cycloaddition (CuAAC) results in stabilized cRGD-functionalized micelle pH nanosensors. In the postmicelle modification strategy, simultaneous cross-linking and fluorophore conjugation...

  17. Dissipative Particle Dynamics Study on Aggregation of MPEG- PAE-PLA Block Polymer Micelles Loading Doxorubicine

    Institute of Scientific and Technical Information of China (English)

    杨楚芬; 孙尧; 章莉娟; 朱国典; 张灿阳; 钱宇

    2012-01-01

    To guide the molecular design of the pH-sensitive triblock amphiphilic polymer MPEG-PAE-PLA and the for- mula design of its doxorubicine (DOX)-loaded micelles, dissipative particle dynamics (DPD) simulations are em- ployed to investigate the aggregation behaviors of the DOX-loaded micelles. The simulation results showed that the aggregate morphologies of micelles and DOX distribution are influenced by degree of polymerization of blocks, and the proposed structure of polymer is MPEG44-PAE3-PLA4. With different contents of polymer or DOX, differ- ent aggregate morphologies of the micelles, like microsphere, spindle/column, reticulation or lamella are observed. To prepare the micro-spherical DOX-loaded micelles, the polymer content is proposed as 10%--15%, and the DOX content less than 10%.

  18. Tuning intermicellar potential of Triton X-100– anthranilic acid mixed micelles

    Indian Academy of Sciences (India)

    Gunjan Verma; V K Aswal; S K Kulshreshtha; C Manohar; P A Hassan; Eric W Kaler

    2008-11-01

    Structural parameters of micelles formed by Triton X-100 in the presence of solubilized anthranilic acid at different pH values was investigated using light scattering and small angle neutron scattering. Analysis of the SANS data indicate that micelles are oblate ellipsoidal in nature with little variation in the dimensions, in the investigated pH range (from 0.5 to 6.0). The interaction potential of the micelles shows a minimum closer to the isoelectric point of anthranilic acid. A similar variation is observed in the cloud point of the micelles with pH. The observed variation in the interaction potential with pH of the micellar solution can be explained in terms of the reversal of charge on anthranilic acid due to shift in the acid–base equilibrium. The variation in interaction potential and cloud point with pH is modelled using Coulombic repulsion of charged molecules at the micelle interface.

  19. Tuning Cationic Block Copolymer Micelle Size by pH and Ionic Strength.

    Science.gov (United States)

    Sprouse, Dustin; Jiang, Yaming; Laaser, Jennifer E; Lodge, Timothy P; Reineke, Theresa M

    2016-09-12

    The formation, morphology, and pH and ionic strength responses of cationic block copolymer micelles in aqueous solutions have been examined in detail to provide insight into the future development of cationic micelles for complexation with polyanions such as DNA. Diblock polymers composed of a hydrophilic/cationic block of N,N-dimethylaminoethyl methacrylate (DMAEMA) and a hydrophobic/nonionic block of n-butyl methacrylate (BMA) were synthesized [denoted as DMAEMA-b-BMA (X-Y), where X = DMAEMA molecular weight and Y = molecular weight of BMA in kDa]. Four variants were created with block molecular weights of 14-13, 14-23, 27-14, 27-29 kDa and low dispersities less than 1.10. The amphiphilic polymers self-assembled in aqueous conditions into core-shell micelles that ranged in size from 25-80 nm. These cationic micelles were extensively characterized in terms of size and net charge in different buffers over a wide range of ionic strength (0.02-1 M) and pH (5-10) conditions. The micelle core is kinetically trapped, and the corona contracts with increasing pH and ionic strength, consistent with previous work on micelles with glassy polystyrene cores, indicating that the corona properties are independent of the dynamics of the micelle core. The contraction and extension of the corona scales with solution ionic strength and charge fraction of the amine groups. The aggregation numbers of the micelles were obtained by static light scattering, and the Rg/Rh ratios are close to that of a hard sphere. The zeta potentials of the micelles were positive up to two pH units above the corona pKa, suggesting that applications relying on micelle charge for stability should be viable over a wide range of solution conditions. PMID:27487088

  20. Vitamin E succinate-conjugated F68 micelles for mitoxantrone delivery in enhancing anticancer activity

    Science.gov (United States)

    Liu, Yuling; Xu, Yingqi; Wu, Minghui; Fan, Lijiao; He, Chengwei; Wan, Jian-Bo; Li, Peng; Chen, Meiwan; Li, Hui

    2016-01-01

    Mitoxantrone (MIT) is a chemotherapeutic agent with promising anticancer efficacy. In this study, Pluronic F68-vitamine E succinate (F68-VES) amphiphilic polymer micelles were developed for delivering MIT and enhancing its anticancer activity. MIT-loaded F68–VES (F68–VES/MIT) micelles were prepared via the solvent evaporation method with self-assembly under aqueous conditions. F68–VES/MIT micelles were found to be of optimal particle size with the narrow size distribution. Transmission electron microscopy images of F68–VES/MIT micelles showed homogeneous spherical shapes and smooth surfaces. F68–VES micelles had a low critical micelle concentration value of 3.311 mg/L, as well as high encapsulation efficiency and drug loading. Moreover, F68–VES/MIT micelles were stable in the presence of fetal bovine serum for 24 hours and maintained sustained drug release in vitro. Remarkably, the half maximal inhibitory concentration (IC50) value of F68–VES/MIT micelles was lower than that of free MIT in both MDA-MB-231 and MCF-7 cells (two human breast cancer cell lines). In addition, compared with free MIT, there was an increased trend of apoptosis and cellular uptake of F68–VES/MIT micelles in MDA-MB-231 cells. Taken together, these results indicated that F68–VES polymer micelles were able to effectively deliver MIT and largely improve its potency in cancer therapy. PMID:27471384

  1. Modulation of ROS production in human leukocytes by ganglioside micelles

    Directory of Open Access Journals (Sweden)

    M. Gavella

    2010-10-01

    Full Text Available Recent studies have reported that exogenous gangliosides, the sialic acid-containing glycosphingolipids, are able to modulate many cellular functions. We examined the effect of micelles of mono- and trisialoganglioside GM1 and GT1b on the production of reactive oxygen species by stimulated human polymorphonuclear neutrophils using different spectroscopic methods. The results indicated that exogenous gangliosides did not influence extracellular superoxide anion (O2.- generation by polymorphonuclear neutrophils activated by receptor-dependent formyl-methionyl-leucyl-phenylalanine. However, when neutrophils were stimulated by receptor-bypassing phorbol 12-myristate 13-acetate (PMA, gangliosides above their critical micellar concentrations prolonged the lag time preceding the production in a concentration-dependent way, without affecting total extracellular O2.- generation detected by superoxide dismutase-inhibitable cytochrome c reduction. The effect of ganglioside GT1b (100 µM on the increase in lag time was shown to be significant by means of both superoxide dismutase-inhibitable cytochrome c reduction assay and electron paramagnetic resonance spectroscopy (P < 0.0001 and P < 0.005, respectively. The observed phenomena can be attributed to the ability of ganglioside micelles attached to the cell surface to slow down PMA uptake, thus increasing the diffusion barrier and consequently delaying membrane events responsible for PMA-stimulated O2.- production.

  2. Encapsulation of GFP in Complex Coacervate Core Micelles.

    Science.gov (United States)

    Nolles, Antsje; Westphal, Adrie H; de Hoop, Jacob A; Fokkink, Remco G; Kleijn, J Mieke; van Berkel, Willem J H; Borst, Jan Willem

    2015-05-11

    Protein encapsulation with polymers has a high potential for drug delivery, enzyme protection and stabilization. Formation of such structures can be achieved by the use of polyelectrolytes to generate so-called complex coacervate core micelles (C3Ms). Here, encapsulation of enhanced green fluorescent protein (EGFP) was investigated using a cationic-neutral diblock copolymer of two different sizes: poly(2-methyl-vinyl-pyridinium)41-b-poly(ethylene-oxide)205 and poly(2-methyl-vinyl-pyridinium)128-b-poly(ethylene-oxide)477. Dynamic light scattering and fluorescence correlation spectroscopy (FCS) revealed a preferred micellar composition (PMC) with a positive charge composition of 0.65 for both diblock copolymers and micellar hydrodynamic radii of approximately 34 nm. FCS data show that at the PMC, C3Ms are formed above 100 nM EGFP, independent of polymer length. Mixtures of EGFP and nonfluorescent GFP were used to quantify the amount of GFP molecules per C3M, resulting in approximately 450 GFPs encapsulated per micelle. This study shows that FCS can be successfully applied for the characterization of protein-containing C3Ms.

  3. Molecular exchange in block copolymer micelles: when corona chains overlap

    Science.gov (United States)

    Lu, Jie; Lodge, Timothy; Bates, Frank; Choi, Soohyung

    2013-03-01

    The chain exchange kinetics of poly(styrene-b-ethylenepropylene) (PS-PEP) diblock copolymer micelles in squalane (C30H62) was investigated using time-resolved small angle neutron scattering (TR-SANS). The solvent is a mixture of h-squalane and d-squalane that contrast-matches a mixed 50/50 h/d PS micelle core. As isotope labeled chains exchange, the core contrast decreases, leading to a reduction in scattering intensity. This strategy therefore allows direct probing of the chain exchange rate. Separate copolymer micellar solutions containing either deuterium labeled (dPS) or normal (hPS) poly(styrene) core blocks were prepared and mixed at room temperature, below the core glass transition temperature. The samples were heated to several temperatures (around 100 °C) and monitored by TR-SANS every 5 min. As polymer concentration was increased from 1% to 15% by volume, we observed a significant slowing down of chain exchange rate. Similar retarded kinetics was found when part of the solvent in the 1% solution was replaced by homopolymer PEP (comparable size as corona block). Furthermore, if all the solvent is replaced with PEP, no exchange was detected for up to 3hr at 200 °C. These results will be discussed in terms of a molecular model for chain exchange Infineum, Iprime, NIST, ORNL

  4. pH-Responsive Micelle Sequestrant Polymers Inhibit Fat Absorption.

    Science.gov (United States)

    Qian, Jian; Sullivan, Bradley P; Berkland, Cory

    2015-08-10

    Current antiobesity therapeutics are associated with side effects and/or poor long-term patient compliance, necessitating development of more efficacious and safer alternatives. Herein, we designed and engineered a new class of orally acting pharmaceutical agents, or micelle sequestrant polymers (MSPs), that could respond to the pH change in the gastrointestinal (GI) tract and potentially sequester lipid micelles; inhibiting lipid absorption through a pH-triggered flocculation process. These MSPs, derived from poly(2-(diisopropylamino)ethyl methacrylate) and poly(2-(dibutylamino)ethyl methacrylate), were soluble in acidic media, but they transitioned to become insoluble around pH 7.2 and 6.1, respectively. MSPs showed substantial bile acid and triglyceride sequestration capacity with fast pH response tested in vitro. In vivo study showed that orally dosed MSPs significantly enhanced fecal elimination of triglycerides and bile acids. Several MSPs increased fecal elimination of triglycerides by 9-10 times compared with that of the control. In contrast, fecal concentration of bile acids, but not triglycerides, was increased by cholestyramine or Welchol. Importantly, fecal elimination of bile acids and triglycerides was unaltered by addition of control dietary fibers. MSPs may serve as a novel approach to weight loss that inhibits excess caloric intake by preventing absorption of excess dietary triglycerides.

  5. Skin delivery by block copolymer nanoparticles (block copolymer micelles).

    Science.gov (United States)

    Laredj-Bourezg, Faiza; Bolzinger, Marie-Alexandrine; Pelletier, Jocelyne; Valour, Jean-Pierre; Rovère, Marie-Rose; Smatti, Batoule; Chevalier, Yves

    2015-12-30

    Block copolymer nanoparticles often referred to as "block copolymer micelles" have been assessed as carriers for skin delivery of hydrophobic drugs. Such carriers are based on organic biocompatible and biodegradable materials loaded with hydrophobic drugs: poly(lactide)-block-poly(ethylene glycol) copolymer (PLA-b-PEG) nanoparticles that have a solid hydrophobic core made of glassy poly(d,l-lactide), and poly(caprolactone)-block-poly(ethylene glycol) copolymer (PCL-b-PEG) nanoparticles having a liquid core of polycaprolactone. In vitro skin absorption of all-trans retinol showed a large accumulation of retinol in stratum corneum from both block copolymer nanoparticles, higher by a factor 20 than Polysorbate 80 surfactant micelles and by a factor 80 than oil solution. Additionally, skin absorption from PLA-b-PEG nanoparticles was higher by one order of magnitude than PCL-b-PEG, although their sizes (65nm) and external surface (water-swollen PEG layer) were identical as revealed by detailed structural characterizations. Fluorescence microscopy of histological skin sections provided a non-destructive picture of the storage of Nile Red inside stratum corneum, epidermis and dermis. Though particle cores had a different physical states (solid or liquid as measured by (1)H NMR), the ability of nanoparticles for solubilization of the drug assessed from their Hildebrand solubility parameters appeared the parameter of best relevance regarding skin absorption.

  6. Construction of phospholipid anti-biofouling multilayer on biomedical PET surfaces

    International Nuclear Information System (INIS)

    The biomimetic phospholipid anti-biofouling multilayers were constructed on the biomedical poly(ethylene terephthalate) (PET) through the combination of layer-by-layer assembly and Michael addition reaction. Two biomacromolecules with opposite charges, alginate and chitosan, were sequentially adsorbed onto PET samples. The assembled multilayer was subsequently crosslinked with glutaraldehyde and biomimetic phospholipids was introduced into the assembled multilayer through the Michael addition of 2-methacryloyloxyethyl phosphorylcholine (MPC). The multilayer and phospholipid-modified PETs showed excellent hemocompatibility

  7. Phorbol esters promote alpha 1-adrenergic receptor phosphorylation and receptor uncoupling from inositol phospholipid metabolism.

    OpenAIRE

    Leeb-Lundberg, L M; Cotecchia, S; Lomasney, J W; DeBernardis, J F; Lefkowitz, R J; Caron, M G

    1985-01-01

    DDT1 MF-2 cells, which are derived from hamster vas deferens smooth muscle, contain alpha 1-adrenergic receptors (54,800 +/- 2700 sites per cell) that are coupled to stimulation of inositol phospholipid metabolism. Incubation of these cells with tumor-promoting phorbol esters, which stimulate calcium- and phospholipid-dependent protein kinase, leads to a marked attenuation of the ability of alpha 1-receptor agonists such as norepinephrine to stimulate the turnover of inositol phospholipids. T...

  8. Adsorption characteristics of uranyl ions onto micelle surface for treatment of radioactive liquid wastes by micelle enhanced ultrafiltration technique

    Energy Technology Data Exchange (ETDEWEB)

    Lee, K. W.; Choi, W. K.; Jeong, K. H.; Lee, D. K.; Jeong, K. J. [KAERI, Taejon (Korea, Republic of)

    2001-10-01

    The objective of this investigation is to establish the rejection behavior of uranium bearing waste water by micelle enhanced ultrafiltration technique. An extensive experimental investigation was conducted with uranium only and uranium in the presence of electrolyte, utilizing ultrasfiltration stirred cell. The effects of experimental parameters such as solution pH and concentration of uranium on rejection were examined from the change of micelle concentration. The rejection dependence of the uranium was found to be a function of pH and uranium to surfactant concentration ratio. Over 95% removal was observed at pH 3 {approx} 5 and SDS concentration of 40 mM. In the presence of electrolytes, the rejection of uranium was observed to decrease significantly, the addition of cobalt ion showed more reduction than that obtained by presence of sodium and cesium ions on rejection of uranium. The rejection behavior was explained in terms of apparent distribution constants. The rejection efficiencies of uranyl ions was significantly affected by the chemical species of the given system. For all cases, the rejection was highly dependent on uranium complex species.

  9. Formation of oil-in-water emulsions from natural emulsifiers using spontaneous emulsification: sunflower phospholipids.

    Science.gov (United States)

    Komaiko, Jennifer; Sastrosubroto, Ashtri; McClements, David Julian

    2015-11-18

    This study examined the possibility of producing oil-in-water emulsions using a natural surfactant (sunflower phospholipids) and a low-energy method (spontaneous emulsification). Spontaneous emulsification was carried out by titrating an organic phase (oil and phospholipid) into an aqueous phase with continuous stirring. The influence of phospholipid composition, surfactant-to-oil ratio (SOR), initial phospholipids location, storage time, phospholipid type, and preparation method was tested. The initial droplet size depended on the nature of the phospholipid used, which was attributed to differences in phospholipid composition. Droplet size decreased with increasing SOR and was smallest when the phospholipid was fully dissolved in the organic phase rather than the aqueous phase. The droplets formed using spontaneous emulsification were relatively large (d > 10 μm), and so the emulsions were unstable to gravitational separation. At low SORs (0.1 and 0.5), emulsions produced with phospholipids had a smaller particle diameter than those produced with a synthetic surfactant (Tween 80), but at a higher SOR (1.0), this trend was reversed. High-energy methods (microfluidization and sonication) formed significantly smaller droplets (d < 10 μm) than spontaneous emulsification. The results from this study show that low-energy methods could be utilized with natural surfactants for applications for which fine droplets are not essential.

  10. Proton NMR study of the interactions of catecholamines with phospholipids from chicken erythrocyte membranes

    Energy Technology Data Exchange (ETDEWEB)

    Varoucha, D.

    1985-01-01

    High-resolution NMR spectroscopy has been applied to the study of the interaction of catecholamines, norepinephrine, epinephrine, isoproterenol and their antagonists propranolol and alprenolol with sonicated phospholipids extracted from chicken erythrocyte membranes (CEM). The catecholamine molecules are immobilized by the phospholipids of CEM and the magnitude of the effect seems to depend on the alkyl substitution of their amino group. Upon introduction of alprenolol and propranolol into phospholipid vesicles a broadening of the resonances of the n-methyl alkyl chain and the terminal methyl protons was observed. The results present evidence about the specificity of the interactions of catecholamines with phospholipids from CEM.

  11. Update on anti-phospholipid antibodies in SLE: the Hopkins' Lupus Cohort.

    Science.gov (United States)

    Petri, M

    2010-04-01

    Anti-phospholipid antibodies are common in patients in the Hopkins' Lupus Cohort: 47% have anti-cardiolipin, 32.5% anti-beta(2)-glycoprotein I and 26% lupus anticoagulant (by dRVVT confirmatory testing). Systemic lupus erythematosus patients with the lupus anticoagulant at baseline have a 50% chance of a deep venous thrombosis/pulmonary embolus in the next 20 years. Anti-phospholipid antibodies differ in their association with thrombosis: the lupus anticoagulant is most strongly associated with arterial and venous thrombosis and is the only anti-phospholipid antibody associated with myocardial infarction. Anti-phospholipid antibodies are not associated with atherosclerosis.

  12. Biodegradable polymeric micelles encapsulated JK184 suppress tumor growth through inhibiting Hedgehog signaling pathway

    Science.gov (United States)

    Zhang, Nannan; Liu, Shichang; Wang, Ning; Deng, Senyi; Song, Linjiang; Wu, Qinjie; Liu, Lei; Su, Weijun; Wei, Yuquan; Xie, Yongmei; Gong, Changyang

    2015-01-01

    JK184 can specially inhibit Gli in the Hedgehog (Hh) pathway, which showed great promise for cancer therapeutics. For developing aqueous formulation and improving anti-tumor activity of JK184, we prepared JK184 encapsulated MPEG-PCL micelles by the solid dispersion method without using surfactants or toxic organic solvents. The cytotoxicity and cellular uptake of JK184 micelles were both increased compared with the free drug. JK184 micelles induced more apoptosis and blocked proliferation of Panc-1 and BxPC-3 tumor cells. In addition, JK184 micelles exerted a sustained in vitro release behavior and had a stronger inhibitory effect on proliferation, migration and invasion of HUVECs than free JK184. Furthermore, JK184 micelles had stronger tumor growth inhibiting effects in subcutaneous Panc-1 and BxPC-3 tumor models. Histological analysis showed that JK184 micelles improved anti-tumor activity by inducing more apoptosis, decreasing microvessel density and reducing expression of CD31, Ki67, and VEGF in tumor tissues. JK184 micelles showed a stronger inhibition of Gli expression in Hh signaling, which played an important role in pancreatic carcinoma. Furthermore, circulation time of JK184 in blood was prolonged after entrapment in polymeric micelles. Our results suggested that JK184 micelles are a promising drug candidate for treating pancreatic tumors with a highly inhibitory effect on Hh activity.JK184 can specially inhibit Gli in the Hedgehog (Hh) pathway, which showed great promise for cancer therapeutics. For developing aqueous formulation and improving anti-tumor activity of JK184, we prepared JK184 encapsulated MPEG-PCL micelles by the solid dispersion method without using surfactants or toxic organic solvents. The cytotoxicity and cellular uptake of JK184 micelles were both increased compared with the free drug. JK184 micelles induced more apoptosis and blocked proliferation of Panc-1 and BxPC-3 tumor cells. In addition, JK184 micelles exerted a sustained in

  13. Magnetic field alignable domains in phospholipid vesicle membranes containing lanthanides.

    Science.gov (United States)

    Beck, Paul; Liebi, Marianne; Kohlbrecher, Joachim; Ishikawa, Takashi; Rüegger, Heinz; Zepik, Helmut; Fischer, Peter; Walde, Peter; Windhab, Erich

    2010-01-14

    Magnetic fields were applied as a structuring force on phospholipid-based vesicular systems, using paramagnetic lanthanide ions as magnetic handles anchored to the vesicle membrane. Different vesicle formulations were investigated using small angle neutron scattering (SANS) in a magnetic field of up to 8 T, cryo-transmission electron microscopy (cryo-TEM), (31)P NMR spectroscopy, dynamic light scattering (DLS), and permeability measurements with a fluorescent water-soluble marker (calcein). The investigated vesicle formulations consisted usually of 80 mol % of the phospholipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and 20 mol % of a chelator lipid (DMPE-DTPA; 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-diethylenetriaminepentaacetate) with complexed lanthanide ions (Tm(3+), Dy(3+), or La(3+)), and the total lipid concentration was 15 mM. Vesicles containing the paramagnetic lanthanide Tm(3+) or Dy(3+) exhibited a temperature-dependent response to magnetic fields, which can be explained by considering the formation of lipid domains, which upon reaching a critical size become alignable in a magnetic field. The features of this "magnetic field alignable domain model" are as follows: with decreasing temperature (from 30 to 2.5 degrees C) solid domains, consisting mainly of the higher melting phospholipid (DMPE-DTPA.lanthanide), begin to form and grow in size. The domains assemble the large magnetic moments conferred by the lanthanides and orient in magnetic fields. The direction of alignment depends on the type of lanthanide used. The domains orient with their normal parallel to the magnetic field with thulium (Tm(3+)) and perpendicular with dysprosium (Dy(3+)). No magnetic field alignable domains were observed if DMPE-DTPA is replaced either by POPE-DTPA (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine-diethylenetriamine-pentaacetate) or by DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine).

  14. Islet amyloid polypeptide inserts into phospholipid monolayers as monomer.

    Science.gov (United States)

    Engel, Maarten F M; Yigittop, HaciAli; Elgersma, Ronald C; Rijkers, Dirk T S; Liskamp, Rob M J; de Kruijff, Ben; Höppener, Jo W M; Antoinette Killian, J

    2006-02-24

    Amyloid deposits in the pancreatic islets of Langerhans are thought to be a main factor responsible for death of the insulin-producing islet beta-cells in type 2 diabetes. It is hypothesized that beta-cell death is related to interaction of the 37 amino acid residue human islet amyloid polypeptide (hIAPP), the major constituent of islet amyloid, with cellular membranes. However, the mechanism of hIAPP-membrane interactions is largely unknown. Here, we study the nature and the molecular details of the initial step of hIAPP-membrane interactions by using the monolayer technique. It is shown that both freshly dissolved hIAPP and the non-amyloidogenic mouse IAPP (mIAPP) have a pronounced ability to insert into phospholipid monolayers, even at lipid packing conditions that exceed the conditions that occur in biological membranes. In contrast, the fibrillar form of hIAPP has lost the ability to insert. These results, combined with the observations that both the insertion kinetics and the dependence of insertion on the initial surface pressure are similar for freshly dissolved hIAPP and mIAPP, indicate that hIAPP inserts into phospholipid monolayers most likely as a monomer. In addition, our results suggest that the N-terminal part of hIAPP, which is nearly identical with that of mIAPP, is largely responsible for insertion. This is supported by experiments with hIAPP fragments, which show that a peptide consisting of the 19 N-terminal residues of hIAPP efficiently inserts into phospholipid monolayers, whereas an amyloidogenic decapeptide, consisting of residues 20-29 of hIAPP, inserts much less efficiently. The results obtained here suggest that hIAPP monomers might insert with high efficiency in biological membranes in vivo. This process could play an important role as a first step in hIAPP-induced membrane damage in type 2 diabetes. PMID:16403520

  15. Phospholipid and Hydrocarbon Interactions with a Charged Electrode Interface.

    Science.gov (United States)

    Levine, Zachary A; DeNardis, Nadica Ivošević; Vernier, P Thomas

    2016-03-22

    Using a combination of molecular dynamics simulations and experiments we examined the interactions of alkanes and phospholipids at charged interfaces in order to understand how interfacial charge densities affect the association of these two representative molecules with electrodes. Consistent with theory and experiment, these model systems reveal interfacial associations mediated through a combination of Coulombic and van der Waals forces. van der Waals forces, in particular, mediate rapid binding of decane to neutral electrodes. No decane binding was observed at high surface charge densities because of interfacial water polarization, which screens hydrophobic attractions. The positively charged choline moiety of the phospholipid palmitoyloleoylphosphatidylcholine (POPC) is primarily responsible for POPC attraction by a moderately negatively charged electrode. The hydrocarbon tails of POPC interact with the hydrophobic electrode interface similarly to decane. Previously reported electrochemical results confirm these findings by demonstrating bipolar displacement currents from PC vesicles adhering to moderately negatively charged interfaces, originating from the choline interactions observed in simulations. At more negatively charged interfaces, choline-to-surface binding was stronger. In both simulations and experiments the maximal interaction of anionic PS occurs with a positively charged interface, provided that the electrostatic forces outweigh local Lennard-Jones interactions. Direct comparisons between the binding affinities measured in experiments and those obtained in simulations reveal previously unobserved atomic interactions that facilitate lipid vesicle adhesion to charged interfaces. Moreover, the implementation of a charged interface in molecular dynamics simulations provides an alternative method for the generation of large electric fields across phospholipid bilayers, especially for systems with periodic boundary conditions, and may be useful for

  16. Arachidonoyl-Phospholipid Remodeling in Proliferating Murine T Cells

    Directory of Open Access Journals (Sweden)

    Ando Soichiro

    2004-01-01

    Full Text Available Abstract Backgound Previous studies have shown that the functional capacity of T cells may be modulated by the composition of fatty acids within, and the release of fatty acids from membrane phospholipids, particulary containing arachidonic acid (AA. The remodeling of AA within membrane phospholipids of resting and proliferating CD4+ and CD8+ T cells is examined in this study. Results Splenic T cells were cultured in the presence or absence of anti-CD3 mAb for 48 h then labeled with [3H]AA for 20 min. In unstimulated cells, labeled AA was preferentially incorporated into the phosphoglycerides, phosphatidylcholine (PC followed by phosphatidylinositol (PI and phosphatidylethanolamine (PE. During a subsequent chase in unlabeled medium unstimulated CD4+ and CD8+ T cells demonstrated a significant and highly selective transfer of free, labeled AA into the PC pool. In contrast, proliferating CD4+ and CD8+ T cells distributed labeled [3H]AA predominantly into PI followed by PC and PE. Following a chase in AA-free medium, a decline in the content of [3H]AA-PC was observed in association with a comparable increase in [3H]AA-PE. Subsequent studies revealed that the cold AA content of all PE species was increased in proliferating T cells compared with that in non-cycling cells, but that enrichment in AA was observed only in the ether lipid fractions. Finally, proliferating T cells preincubated with [3H]AA exhibited a significant loss of labeled arachidonate in the PC fraction and an equivalent gain in labeled AA in 1-alk-1'-enyl-2-arachidonoyl-PE during a chase in unlabeled medium. Conclusion This apparent unidirectional transfer of AA from PC to ether-containing PE suggests the existence of a CoA-independent transacylase system in T cells and supports the hypothesis that arachidonoyl phospholipid remodeling may play a role in the regulation of cellular proliferation.

  17. A micelle-like structure of poloxamer-methotrexate conjugates as nanocarrier for methotrexate delivery.

    Science.gov (United States)

    Ren, Jin; Fang, Zhengjie; Yao, Li; Dahmani, Fatima Zohra; Yin, Lifang; Zhou, Jianping; Yao, Jing

    2015-06-20

    The purpose of this study was to develop a novel featured and flexible methotrexate (MTX) formulation, in which MTX was physically entrapped and chemically conjugated in the same drug delivery system. A series of poloxamer-MTX (p-MTX) conjugates was synthesized, wherein MTX was grafted to poloxamer through an ester bond. p-MTX conjugates could self-assemble into micelle-like structures in aqueous environment and the MTX end was in the inner-core of micelles. Moreover, free MTX could be physically entrapped into p-MTX micelles hydrophobic core region to increase the total drug loading. Importantly, the resulting MTX-loaded p-MTX micelles showed a biphasic release of MTX, with a relative fast release of the entrapped MTX (about 6-7h) followed by a sustained release of the conjugated MTX. The pharmacokinetics study showed that the mean residence time (MRT) was extended in the case of MTX-loaded p-MTX micelles, indicating a delayed MTX elimination from the bloodstream and prolonged in vivo residence time. Besides, the area under curve (AUC) of MTX-loaded p-MTX micelles was greater than free MTX, indicating a drug bioavailability improvement. Overall, MTX-loaded p-MTX micelles might be a promising nanosized drug delivery system for the cancer therapy.

  18. Production of Fluconazole-Loaded Polymeric Micelles Using Membrane and Microfluidic Dispersion Devices

    Science.gov (United States)

    Lu, Yu; Chowdhury, Danial; Vladisavljević, Goran T.; Koutroumanis, Konstantinos; Georgiadou, Stella

    2016-01-01

    Polymeric micelles with a controlled size in the range between 41 and 80 nm were prepared by injecting the organic phase through a microengineered nickel membrane or a tapered-end glass capillary into an aqueous phase. The organic phase was composed of 1 mg·mL−1 of PEG-b-PCL diblock copolymers with variable molecular weights, dissolved in tetrahydrofuran (THF) or acetone. The pore size of the membrane was 20 μm and the aqueous/organic phase volumetric flow rate ratio ranged from 1.5 to 10. Block copolymers were successfully synthesized with Mn ranging from ~9700 to 16,000 g·mol−1 and polymeric micelles were successfully produced from both devices. Micelles produced from the membrane device were smaller than those produced from the microfluidic device, due to the much smaller pore size compared with the orifice size in a co-flow device. The micelles were found to be relatively stable in terms of their size with an initial decrease in size attributed to evaporation of residual solvent rather than their structural disintegration. Fluconazole was loaded into the cores of micelles by injecting the organic phase composed of 0.5–2.5 mg·mL−1 fluconazole and 1.5 mg·mL−1 copolymer. The size of the drug-loaded micelles was found to be significantly larger than the size of empty micelles. PMID:27231945

  19. Production of Fluconazole-Loaded Polymeric Micelles Using Membrane and Microfluidic Dispersion Devices

    Directory of Open Access Journals (Sweden)

    Yu Lu

    2016-05-01

    Full Text Available Polymeric micelles with a controlled size in the range between 41 and 80 nm were prepared by injecting the organic phase through a microengineered nickel membrane or a tapered-end glass capillary into an aqueous phase. The organic phase was composed of 1 mg·mL−1 of PEG-b-PCL diblock copolymers with variable molecular weights, dissolved in tetrahydrofuran (THF or acetone. The pore size of the membrane was 20 μm and the aqueous/organic phase volumetric flow rate ratio ranged from 1.5 to 10. Block copolymers were successfully synthesized with Mn ranging from ~9700 to 16,000 g·mol−1 and polymeric micelles were successfully produced from both devices. Micelles produced from the membrane device were smaller than those produced from the microfluidic device, due to the much smaller pore size compared with the orifice size in a co-flow device. The micelles were found to be relatively stable in terms of their size with an initial decrease in size attributed to evaporation of residual solvent rather than their structural disintegration. Fluconazole was loaded into the cores of micelles by injecting the organic phase composed of 0.5–2.5 mg·mL−1 fluconazole and 1.5 mg·mL−1 copolymer. The size of the drug-loaded micelles was found to be significantly larger than the size of empty micelles.

  20. Spectral Properties and Solubilization Location of 2'-Ethylhexyl 4-(N,N-Dimethylamino)benzoate in Micelles

    Institute of Scientific and Technical Information of China (English)

    Ning Ding; Xin-zhen Du; Chun Wang; Xiao-quan Lu

    2008-01-01

    Dual fluorescence and UV absorption of 2'-ethylhexyl 4-(N,N-dimethylamino)benzoate (EHDMAB) were investigated in cationic,non-ionic and anionic miceUes.When EHDMAB was solubilized in different micellss, the UV absorption of EHDMAB was enhanced.Twisted intramolecular charge transfer (TICT) emission with longer wavelength was observed in ionic micelles,whereas TICT emission with shorter wavelength was obtained in non-ionic micelles.In particular,dual fluorescence of EHDMAB was significantly quenched by the positively charged pyridinium ions arranged in the Stern layer of cationic micelles.UV radiation absorbed mainly decays via TICT emission and radiationless deactivation.The dimethylamino group of EHDMAB experiences different polar environments in ionic and non-ionic micelles according to the polarity dependence of TICT emission of EHDMAB in organic solvents.In terms of the molecular structures and sizes of EHDMAB and surfactants,each individual EHDMAB molecule should be buried in micelles with its dimethylamino group toward the polar head groups of different micelles and with its 2'-ethylhexyl chain toward the hydrophobic micellar core.Dynamic fluorescence quenching measurements of EHDMAB provide further support for the location of EHDMAB in different micelles.

  1. Octreotide-functionalized and resveratrol-loaded unimolecular micelles for targeted neuroendocrine cancer therapy

    Science.gov (United States)

    Xu, Wenjin; Burke, Jocelyn F.; Pilla, Srikanth; Chen, Herbert; Jaskula-Sztul, Renata; Gong, Shaoqin

    2013-09-01

    Medullary thyroid cancer (MTC) is a neuroendocrine tumor (NET) that is often resistant to standard therapies. Resveratrol suppresses MTC growth in vitro, but it has low bioavailability in vivo due to its poor water solubility and rapid metabolic breakdown, as well as lack of tumor-targeting ability. A novel unimolecular micelle based on a hyperbranched amphiphilic block copolymer was designed, synthesized, and characterized for NET-targeted delivery. The hyperbranched amphiphilic block copolymer consisted of a dendritic Boltorn® H40 core, a hydrophobic poly(l-lactide) (PLA) inner shell, and a hydrophilic poly(ethylene glycol) (PEG) outer shell. Octreotide (OCT), a peptide that shows strong binding affinity to somatostatin receptors, which are overexpressed on NET cells, was used as the targeting ligand. Resveratrol was physically encapsulated by the micelle with a drug loading content of 12.1%. The unimolecular micelles exhibited a uniform size distribution and spherical morphology, which were determined by both transmission electron microscopy (TEM) and dynamic light scattering (DLS). Cellular uptake, cellular proliferation, and Western blot analyses demonstrated that the resveratrol-loaded OCT-targeted micelles suppressed growth more effectively than non-targeted micelles. Moreover, resveratrol-loaded NET-targeted micelles affected MTC cells similarly to free resveratrol in vitro, with equal growth suppression and reduction in NET marker production. These results suggest that the H40-based unimolecular micelle may offer a promising approach for targeted NET therapy.

  2. Effect of the lipid chain melting transition on the stability of DSPE-PEG(2000) micelles.

    Science.gov (United States)

    Kastantin, Mark; Ananthanarayanan, Badriprasad; Karmali, Priya; Ruoslahti, Erkki; Tirrell, Matthew

    2009-07-01

    Micellar nanoparticles are showing promise as carriers of diagnostic and therapeutic biofunctionality, leading to increased interest in their properties and behavior, particularly their size, shape, and stability. This work investigates the physical chemistry of micelles formed from DSPE-PEG(2000) monomers as it pertains to these properties. A melting transition in the lipid core of spheroidal DSPE-PEG(2000) micelles is observed as an endothermic peak at 12.8 degrees C upon heating in differential scanning calorimetry thermograms. Bulky PEG(2000) head groups prevent regular crystalline packing of lipids in both the low-temperature glassy and high-temperature fluid phases, as evidenced by wide-angle X-ray scattering. Equilibrium micelle geometry is spheroidal above and below the transition temperature, indicating that the entropic penalty to force the PEG brush into flat geometry is greater than the enthalpic benefit to the glassy core to pack in an extended configuration. Increased micelle stability is seen in the glassy phase with monomer desorption rates significantly lower than in the fluid phase. Activation energies for monomer desorption are 156+/-6.7 and 79+/-5.0 kJ/mol for the glassy and fluid phases, respectively. The observation of a glass transition that increases micelle stability but does not perturb micelle geometry is useful for the design of more effective biofunctional micelles.

  3. Cholesterol-Enhanced Polylactide-Based Stereocomplex Micelle for Effective Delivery of Doxorubicin

    Directory of Open Access Journals (Sweden)

    Jixue Wang

    2015-01-01

    Full Text Available Nanoscale micelles as an effective drug delivery system have attracted increasing interest in malignancy therapy. The present study reported the construction of the cholesterol-enhanced doxorubicin (DOX-loaded poly(D-lactide-based micelle (CDM/DOX, poly(L-lactide-based micelle (CLM/DOX, and stereocomplex micelle (CSCM/DOX from the equimolar enantiomeric 4-armed poly(ethylene glycol–polylactide copolymers in aqueous condition. Compared with CDM/DOX and CLM/DOX, CSCM/DOX showed the smallest hydrodynamic size of 96 ± 4.8 nm and the slowest DOX release. The DOX-loaded micelles exhibited a weaker DOX fluorescence inside mouse renal carcinoma cells (i.e., RenCa cells compared to free DOX·HCl, probably because of a slower DOX release. More importantly, all the DOX-loaded micelles, especially CSCM/DOX, exhibited the excellent antiproliferative efficacy that was equal to or even better than free DOX·HCl toward RenCa cells attributed to their successful internalization. Furthermore, all of the DOX-loaded micelles exhibited the satisfactory hemocompatibility compared to free DOX·HCl, indicating the great potential for systemic chemotherapy through intravenous injection.

  4. Study of sodium dodecyl sulfate-poly(propylene oxide) methacrylate mixed micelles.

    Science.gov (United States)

    Bastiat, Guillaume; Grassl, Bruno; Khoukh, Abdel; François, Jeanne

    2004-07-01

    Sodium dodecyl sulfate (SDS)-poly(propylene oxide) methacrylate (PPOMA) (of molecular weight M(w) = 434 g x mol(-1)) mixtures have been studied using conductimetry, static light scattering, fluorescence spectroscopy, and 1H NMR. It has been shown that SDS and PPOMA form mixed micelles, and SDS and PPOMA aggregation numbers, N(ag SDS) and N(ag PPOMA), have been determined. Total aggregation numbers of the micelles (N(ag SDS) + N(ag PPOMA)) and those of SDS decrease upon increasing the weight ratio R = PPOMA/SDS. Localization of PPOMA inside the mixed micelles is considered (i) using 1H NMR to localize the methacrylate function at the hydrophobic core-water interface and (ii) by studying the SDS-PPO micellar system (whose M(w) = 400 g x mol(-1)). Both methods have indicated that the PPO chain of the macromonomer is localized at the SDS micelle surface. Models based on the theorical prediction of the critical micellar concentration of mixed micelles and structural model of swollen micelles are used to confirm the particular structure proposed for the SDS-PPOMA system, i.e., the micelle hydrophobic core is primarily composed of the C12 chains of the sodium dodecyl sulfate, the hydrophobic core-water interface is made up of the SDS polar heads as well as methacrylate functions of the PPOMA, the PPO chains of the macromonomer are adsorbed preferentially on the surface, i.e., on the polar heads of the SDS.

  5. Phospholipid bilayer formation at a bare Si surface

    DEFF Research Database (Denmark)

    Gutberlet, T.; Steitz, R.; Fragneto, G.;

    2004-01-01

    Neutron reflectivity was applied to monitor in situ the adsorption of small unilamellar phospholipid vesicles on a solid bare hydrophilic Si interface. The obtained reflectivity curves are consistent with the rupture and fusion model for the adsorption of phosphatidylcholine vesicles to solid...... interfaces. The results show details of the adsorbed bilayer system at ångström resolution and indicate the presence of a thin ∼6 Å thick water leaflet that separates the bilayer from the Si surface. The resolved structural details provide the basis for further investigation of processes such as adsorption...

  6. Separation of phosphatidylcholine from soybean phospholipids by simulated moving bed

    Institute of Scientific and Technical Information of China (English)

    L(U) Yu-bin; YANG Yi-wen; WU Ping-dong

    2006-01-01

    A simulated moving bed (SMB), equipped with eight silica-gel columns, was used to separate phosphatidylcholine (PC) from soybean phospholipids. The effects of flow rate in Sections 2 (Q2) and 3 (Q3), switching time, feed flow rate and feed concentration on the operating performance parameters: purity, recovery, productivity and desorbent consumption were studied.Operating conditions leading to more than 90% purity in both outlet streams have been identified, together with those achieving optimal performance. Regions leading to complete separation are observed and explained theoretically. As the mass-transfer effect was not considered, the triangle theory only gives initial guesses for the optimal operating conditions.

  7. Mechanics and dynamics of triglyceride-phospholipid model membranes

    DEFF Research Database (Denmark)

    Pakkanen, Kirsi I.; Duelund, Lars; Qvortrup, Klaus;

    2011-01-01

    We demonstrate here that triolein alters the mechanical properties of phospholipid membranes and induces extraordinary conformational dynamics. Triolein containing membranes exhibit fluctuations up to size range of 100µm and with the help of these are e.g. able to squeeze through narrow passages...... with larger lamellar distances observed in the TOPOPC membranes. These findings suggest repulsion between adjacent membranes. We provide a comprehensive discussion on the possible explanations for the observed mechanics and dynamics in the TOPOPC system and on their potential cellular implications....

  8. Polymeric micelles containing reversibly phospholipid-modified anti-survivin siRNA: a promising strategy to overcome drug resistance in cancer

    OpenAIRE

    Salzano, G; Riehle, R.; Navarro, Gemma; Perche, Federico; Rosa, G.; Torchilin, VT

    2013-01-01

    The discovery that survivin, a small anti-apoptotic protein, is involved in chemoresistance, opens a new scenario to overcome the drug resistance in cancer. It was shown that siRNA can efficiently inhibit the expression of survivin in cancer cells. However, the clinical use of siRNA is still hampered by an unfavorable pharmacokinetic profile. To address this problem, earlier we developed a novel system to deliver siRNA into cancer cells. Namely, we reversibly modified the survivin siRNA with ...

  9. Counterion condensation in ionic micelles as studied by a combined use of SANS and SAXS

    Indian Academy of Sciences (India)

    V K Aswal; P S Goyal; H Amenitsch; S Bernstorff

    2004-08-01

    We report a combined use of small-angle neutron scattering (SANS) and small-angle X-ray scattering (SAXS) to the study of counterion condensation in ionic micelles. Small-angle neutron and X-ray scattering measurements have been carried out on two surfactants cetyltrimethylammonium bromide (CTABr) and cetyltrimethylammonium chloride (CTACl), which are similar but having different counterions. SANS measurements show that CTABr surfactant forms much larger micelles than CTACl. This is explained in terms of higher condensation of Br0 counterions than Cl- counterions. SAXS data on these systems suggest that the Br- counterions are condensed around the micelles over smaller thickness than those of Cl- counterions.

  10. Specific tumor delivery of paclitaxel using glycolipid-like polymer micelles containing gold nanospheres.

    Science.gov (United States)

    You, Jian; Wang, Zuhua; Du, Yongzhong; Yuan, Hong; Zhang, Peizun; Zhou, Jialin; Liu, Fei; Li, Chun; Hu, Fuqiang

    2013-06-01

    It is difficult for most of the drug delivery systems to really display a temporal and spatial release of entrapped drug once the systems are iv administrated. We hypothesized that the photothermal effect, mediated by a near-infrared (NIR) laser and hollow gold nanospheres (HAuNS), can modulate paclitaxel (PTX) release from polymer micelles, and further result in the enhanced antitumor activity of the micelles. We loaded PTX and HAuNS, which display strong plasmon absorption in the NIR region, into glycolipid-like polymer micelles with an excellent cell internalization capability. The surface of the micelles was conjugated successfully with a peptide, which has the specific-binding with EphB4, a member of the Eph family of receptor tyrosine kinases overexpressed on cell membrane of numerous tumors, to increase the delivery of PTX into tumor cells. Rapid and repetitive drug release from our polymer (HP-TCS) micelles could be readily achieved upon NIR laser irradiation. Our data demonstrated the specific delivery of HP-TCS micelles into positive-EphB4 tumors using a duel-tumor model after iv administration during the whole experiment process (1-48 h). Interestingly, significantly higher uptake of the micelles by SKOV3 tumors (positive-EphB4) than A549 tumors (negtive-EphB4) was observed, with increased ratio on experiment time. However, the specific cell uptake was observed only during the short incubation time (1-4 h) in vitro. Our data also indicated the treatment of tumor cells with the micelles followed by NIR laser irradiation showed significantly greater toxicity activity than the treatment with the micelles alone, free PTX and the micelles (without PTX loading) plus NIR laser irradiation. The enhanced toxicity activity to tumor cells should be attributed to the enhanced drug cellular uptake mediated by the glycolipid-like micelles, chemical toxicity of the released drug from the micelles due to the trigger of NIR laser, and the photothermal ablation under NIR

  11. pH-responsive layer-by-layer films of zwitterionic block copolymer micelles

    OpenAIRE

    Demirel, Adem Levent; Yusan, Pelin; Tuncel, İrem; Bütün, Vural; Erel-Goktepe, İrem

    2014-01-01

    We report a strategy to incorporate micelles of poly[3-dimethyl (methacryloyloxyethyl) ammonium propane sulfonate]-block-poly[2-(diisopropylamino) ethyl methacrylate] (beta PDMA-b-PDPA) into electrostatic layer-by-layer (LbL) films. We obtained micelles with pH-responsive PDPA-cores and zwitterionic bPDMA-coronae at pH 8.5 through pH-induced self-assembly of bPDMA-b-PDPA in aqueous solution. To incorporate bPDMA-b-PDPA micelles into LbL films, we first obtained a net electrical charge on bPDM...

  12. Sphere-to-rod transition of triblock copolymer micelles at room temperature

    Indian Academy of Sciences (India)

    R Ganguly; V K Aswal; P A Hassan; I K Gopalakrishnan; J V Yakhmi

    2004-08-01

    A room temperature sphere-to-rod transition of the polyethylene oxide-polypropylene oxide-polyethylene oxide-based triblock copolymer, (PEO)20 (PPO)70 (PEO)20 micelles have been observed in aqueous medium under the influence of ethanol and sodium chloride. Addition of 5-10% ethanol induces a high temperature sphere-to-rod transition of the micelles, which is brought to room temperature upon addition of NaCl. The inference about the change in the shape of the micelles has been drawn from small-angle neutron scattering (SANS) and viscosity studies.

  13. Cation-π Interaction between the Aromatic Organic Counterion and DTAB Micelle in Mixed Solvents

    Institute of Scientific and Technical Information of China (English)

    DENG,Dong-Shun(邓东顺); LI,Hao-Ran(李浩然); LIU,Di-Xia(刘迪霞); HAN,Shi-Jun(韩世钧)

    2004-01-01

    The cation-π interaction between the aromatic organic counterion potassium hydrogen phthalate (KHP) and DTAB micelle in aqueous mixture of EG was investigated, using the techniques of conductivity measurements, UV absorption spectrum and NMR spectrum. The conductivity and UV spectrum studies were with respect to the effect of KHP on DTAB and that of DTAB micelle on KHP, respectively. According to the chemical shift changes of the aromatic ring and the surfactant methylene protons, it can be assumed that KHP penetrated into DTAB micelle with its carboxylic group protruding out of the micellar surface. And the strength of the interaction became weaker with the content of EG in the mixed solvent increasing.

  14. The elasticity of soap bubbles containing wormlike micelles.

    Science.gov (United States)

    Sabadini, Edvaldo; Ungarato, Rafael F S; Miranda, Paulo B

    2014-01-28

    Slow-motion imaging of the rupture of soap bubbles generally shows the edges of liquid films retracting at a constant speed (known as the Taylor-Culick velocity). Here we investigate soap bubbles formed from simple solutions of a cationic surfactant (cetyltrimethylammonium bromide - CTAB) and sodium salicylate. The interaction of salicylate ions with CTAB leads to the formation of wormlike micelles (WLM), which yield a viscoelastic behavior to the liquid film of the bubble. We demonstrate that these elastic bubbles collapse at a velocity up to 30 times higher than the Taylor-Culick limit, which has never been surpassed. This is because during the bubble inflation, the entangled WLM chains stretch, storing elastic energy. This extra energy is then released during the rupture of the bubble, yielding an additional driving force for film retraction (besides surface tension). This new mechanism for the bursting of elastic bubbles may have important implications to the breakup of viscoelastic sprays in industrial applications. PMID:24401119

  15. Cooperative catalysis with block copolymer micelles: A combinatorial approach

    KAUST Repository

    Bukhryakov, Konstantin V.

    2015-02-09

    A rapid approach to identifying complementary catalytic groups using combinations of functional polymers is presented. Amphiphilic polymers with "clickable" hydrophobic blocks were used to create a library of functional polymers, each bearing a single functionality. The polymers were combined in water, yielding mixed micelles. As the functional groups were colocalized in the hydrophobic microphase, they could act cooperatively, giving rise to new modes of catalysis. The multipolymer "clumps" were screened for catalytic activity, both in the presence and absence of metal ions. A number of catalyst candidates were identified across a wide range of model reaction types. One of the catalytic systems discovered was used to perform a number of preparative-scale syntheses. Our approach provides easy access to a range of enzyme-inspired cooperative catalysts.

  16. Cooperative catalysis with block copolymer micelles: a combinatorial approach.

    Science.gov (United States)

    Bukhryakov, Konstantin V; Desyatkin, Victor G; O'Shea, John-Paul; Almahdali, Sarah R; Solovyeva, Vera; Rodionov, Valentin O

    2015-02-01

    A rapid approach to identifying complementary catalytic groups using combinations of functional polymers is presented. Amphiphilic polymers with "clickable" hydrophobic blocks were used to create a library of functional polymers, each bearing a single functionality. The polymers were combined in water, yielding mixed micelles. As the functional groups were colocalized in the hydrophobic microphase, they could act cooperatively, giving rise to new modes of catalysis. The multipolymer "clumps" were screened for catalytic activity, both in the presence and absence of metal ions. A number of catalyst candidates were identified across a wide range of model reaction types. One of the catalytic systems discovered was used to perform a number of preparative-scale syntheses. Our approach provides easy access to a range of enzyme-inspired cooperative catalysts.

  17. Amino Acids Catalyzed Direct Aldol Reactions in Aqueous Micelles

    Institute of Scientific and Technical Information of China (English)

    PENG Yi-Yuan; WANG Qi; DING Qiu-Ping; HE Jia-Qi; CHENG Jin-Pei

    2003-01-01

    @@ Since the discovery of its roles as a good small-organic-molecule catalyst in intramolecular aldol reactions, pro line has drawn considerable attention in synthetic chemistry due to its similarity to the type-Ⅰ aldolases. Recently,List and others have reported some new direct asymmetric intermolecular reactions catalyzed by proline, including aldol, Mannich, Michael, and other analogous reactions. Except for two recent examples, [1,2] proline catalyzed aldol reactions in aqueous micelles have not been reported, nor have other amino acids as organocatalysts in directly catalyzing aldol reaction been reported. Herein we wish to present our recent results regarding environmentally be nign direct aldol reactions catalyzed by amino acids including proline, histidine and arginine in aqueous media.

  18. Complement monitoring of Pluronic 127 gel and micelles

    DEFF Research Database (Denmark)

    Hamad, Islam; Hunter, A Christy; Moghimi, Seyed Moien

    2013-01-01

    vascular occlusion. We show that poloxamer gel can trigger the complement system, which is an integral part of innate immunity and its inadvertent activation can induce clinically significant anaphylaxis. Complement activation by the poloxamer gel is through the alternative pathway, but material...... transformations from gel to the solution state further incite complement through calcium-sensitive pathways, where a role for C1q and antibodies has been eliminated. Poloxamer addition to plasma/serum (at levels above its critical micelle concentration, cmc) induced formation of large and diffused structures......, which may have been responsible for triggering complement. Since poloxamer 407 administration has been reported to cause significant changes in plasma cholesterol and triglyceride levels we further examined the role of lipoproteins in poloxamer-mediated complement activation. Our results show...

  19. Interleaflet mixing and coupling in liquid-disordered phospholipid bilayers.

    Science.gov (United States)

    Capponi, Sara; Freites, J Alfredo; Tobias, Douglas J; White, Stephen H

    2016-02-01

    Organized as bilayers, phospholipids are the fundamental building blocks of cellular membranes and determine many of their biological functions. Interactions between the two leaflets of the bilayer (interleaflet coupling) have been implicated in the passage of information through membranes. However, physically, the meaning of interleaflet coupling is ill defined and lacks a structural basis. Using all-atom molecular dynamics simulations of fluid phospholipid bilayers of five different lipids with differing degrees of acyl-chain asymmetry, we have examined interleaflet mixing to gain insights into coupling. Reasoning that the transbilayer distribution of terminal methyl groups is an appropriate measure of interleaflet mixing, we calculated the transbilayer distributions of the acyl chain terminal methyl groups for five lipids: dioleoylphosphatidylcholine (DOPC), palmitoyloleoylphosphatidylcholine (POPC), stearoyloleoylphosphatidylcholine (SOPC), oleoylmyristoylphosphatidylcholine (OMPC), and dimyristoylphosphatidylcholine (DMPC). We observed in all cases very strong mixing across the bilayer midplane that diminished somewhat with increasing acyl-chain ordering defined by methylene order parameters. A hallmark of the interleaflet coupling idea is complementarity, which postulates that lipids with short alkyl chains in one leaflet will preferentially associate with lipids with long alkyl chains in the other leaflet. Our results suggest a much more complicated picture for thermally disordered bilayers that we call distributed complementarity, as measured by the difference in the peak positions of the sn-1 and sn-2 methyl distributions in the same leaflet. PMID:26657692

  20. Characterization of the phospholipid methyltransferase in RBC ghost preparations

    International Nuclear Information System (INIS)

    The activity of the phospholipid methyltransferase from human RBC ghosts was studied using radio-HPLC techniques to analyze the products. Both monomethyl phosphatidyl ethanolamine (MMPE) and dimethyl phosphatidyl ethanolamine (DMPE) were used as substrated. The reaction rate was linear for 45 min. Apparent K/sub M/s of 24-28 uM and 19-21 uM were measured for these two substrates, respectively. The reaction rate was not linear with protein. It appeared to increase logarithmic. An apparent K/sub M/ for S-adenosylmethionine was 36-45 uM. These K/sub M/ values are similar to those reported by others for liver. As the concentration of MMPE was increased, the ratio of DMPE/PC also increased due largely to a greater increase in DMPE formation. Optimal reaction rates for the formation of DMPE were 0.9-1.3 pmol/mg/min, and an optimal rate of about 1.7-2.4 pmol/min/mg was measured for the conversion of DMPE to phosphatidyl choline (PC). Freezing the ghost preparation did not affect the activity of the enzyme. When no exogenous phospholipid was added to the incubation, the sum of the formation rates of all three methylated products was about 26 pmol/mg/hr. The relative amount of each product was 46% MMPE, 32% DMPE and 22% PC. When either MMPE or DMPE was added as substrate, the formation of MMPE was reduced to less than 1%

  1. Spontaneous structural transition in phospholipid-inspired aromatic phosphopeptide nanostructures.

    Science.gov (United States)

    Pellach, Michal; Atsmon-Raz, Yoav; Simonovsky, Eyal; Gottlieb, Hugo; Jacoby, Guy; Beck, Roy; Adler-Abramovich, Lihi; Miller, Yifat; Gazit, Ehud

    2015-01-01

    Phospholipid membranes could be considered a prime example of the ability of nature to produce complex yet ordered structures, by spontaneous and efficient self-assembly. Inspired by the unique properties and architecture of phospholipids, we designed simple amphiphilic decapeptides, intended to fold in the center of the peptide sequence, with a phosphorylated serine "head" located within a central turn segment, and two hydrophobic "tails". The molecular design also included the integration of the diphenylalanine motif, previously shown to facilitate self-assembly and increase nanostructure stability. Secondary structure analysis of the peptides indeed indicated the presence of stabilized conformations in solution, with a central turn connecting two hydrophobic "tails", and interactions between the hydrophobic strands. The mechanisms of assembly into supramolecular structures involved structural transitions between different morphologies, which occurred over several hours, leading to the formation of distinctive nanostructures, including half-elliptical nanosheets and curved tapes. The phosphopeptide building blocks appear to self-assemble via a particular combination of aromatic, hydrophobic and ionic interactions, as well as hydrogen bonding, as demonstrated by proposed constructed simulated models of the peptides and self-assembled nanostructures. Molecular dynamics simulations also gave insight into mechanisms of structural transitions of the nanostructures at a molecular level. Because of the biocompatibility of peptides, the phosphopeptide assemblies allow for expansion of the library of biomolecular nanostructures available for future design and application of biomedical devices. PMID:25802000

  2. Structure and organization of phospholipid/polysaccharide nanoparticles

    International Nuclear Information System (INIS)

    In recent years nanoparticles and microparticles composed of polymeric or lipid material have been proposed as drug carriers for improving the efficacy of encapsulated drugs. For the production of these systems different materials have been proposed, among them phospholipids and polysaccharides due to their biocompatibility, biodegradability, low cost and safety. We report here a morphological and structural investigation, performed using cryo-TEM, static light scattering and small angle neutron and x-ray scattering, on phospholipid/saccharide nanoparticles loaded with a lipophilic positively charged drug (tamoxifen citrate) used in breast cancer therapy. The lipid component was soybean lecithin; the saccharide one was chitosan that usually acts as an outer coating increasing vesicle stability. The microscopy and scattering data indicate the presence of two distinct nanoparticle families: uni-lamellar vesicles with average radius 90 A and multi-lamellar vesicles with average radius 440 A. In both families the inner core is occupied by the solvent. The presence of tamoxifen gives rise to a multi-lamellar structure of the lipid outer shell. It also induces a positive surface charge into the vesicles, repelling the positively charged chitosan molecules which therefore do not take part in nanoparticle formation

  3. Mutagenicity of diesel exhaust soot dispersed in phospholipid surfactants

    Energy Technology Data Exchange (ETDEWEB)

    Wallace, W.; Keane, M.; Xing, S.; Harrison, J.; Gautam, M.; Ong, T.

    1994-06-01

    Organics extractable from respirable diesel exhaust soot particles by organic solvents have been known for some time to be direct acting frameshift mutagens in the Ames Salmonella typhimurium histidine reversion assay. Upon deposition in a pulmonary alveolus or respiratory bronchiole, respirable diesel soot particles will contact first the hypophase which is coated by and laden with surfactants. To model interactions of soot and pulmonary surfactant, the authors dispersed soots in vitro in the primary phospholipid pulmonary surfactant dipalmitoyl glycerophosphorylcholine (lecithin) (DPL) in physiological saline. They have shown that diesel soots dispersed in lecithin surfactant can express mutagenic activity, in the Ames assay system using S. typhimurium TA98, comparable to that expressed by equal amounts of soot extracted by dichloromethane/dimethylsulfoxide (DCM/DMSO). Here the authors report additional data on the same system using additional exhaust soots and also using two other phospholipids, dipalmitoyl glycerophosphoryl ethanolamine (DPPE), and dipalmitoyl phosphatidic acid (DPPA), with different ionic character hydrophilic moieties. A preliminary study of the surfactant dispersed soot in an eucaryotic cell test system also is reported.

  4. Cationic Polyene Phospholipids as DNA Carriers for Ocular Gene Therapy

    Directory of Open Access Journals (Sweden)

    Susana Machado

    2014-01-01

    Full Text Available Recent success in the treatment of congenital blindness demonstrates the potential of ocular gene therapy as a therapeutic approach. The eye is a good target due to its small size, minimal diffusion of therapeutic agent to the systemic circulation, and low immune and inflammatory responses. Currently, most approaches are based on viral vectors, but efforts continue towards the synthesis and evaluation of new nonviral carriers to improve nucleic acid delivery. Our objective is to evaluate the efficiency of novel cationic retinoic and carotenoic glycol phospholipids, designated C20-18, C20-20, and C30-20, to deliver DNA to human retinal pigmented epithelium (RPE cells. Liposomes were produced by solvent evaporation of ethanolic mixtures of the polyene compounds and coformulated with 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE or cholesterol (Chol. Addition of DNA to the liposomes formed lipoplexes, which were characterized for binding, size, biocompatibility, and transgene efficiency. Lipoplex formulations of suitable size and biocompatibility were assayed for DNA delivery, both qualitatively and quantitatively, using RPE cells and a GFP-encoding plasmid. The retinoic lipoplex formulation with DOPE revealed a transfection efficiency comparable to the known lipid references 3β-[N-(N′,N′-dimethylaminoethane-carbamoyl]-cholesterol (DC-Chol and 1,2-dioleoyl-sn-glycero-3-ethylphosphocholine (EPC and GeneJuice. The results demonstrate that cationic polyene phospholipids have potential as DNA carriers for ocular gene therapy.

  5. Structure and organization of phospholipid/polysaccharide nanoparticles

    Science.gov (United States)

    Gerelli, Y.; Di Bari, M. T.; Deriu, A.; Cantù, L.; Colombo, P.; Como, C.; Motta, S.; Sonvico, F.; May, R.

    2008-03-01

    In recent years nanoparticles and microparticles composed of polymeric or lipid material have been proposed as drug carriers for improving the efficacy of encapsulated drugs. For the production of these systems different materials have been proposed, among them phospholipids and polysaccharides due to their biocompatibility, biodegradability, low cost and safety. We report here a morphological and structural investigation, performed using cryo-TEM, static light scattering and small angle neutron and x-ray scattering, on phospholipid/saccharide nanoparticles loaded with a lipophilic positively charged drug (tamoxifen citrate) used in breast cancer therapy. The lipid component was soybean lecithin; the saccharide one was chitosan that usually acts as an outer coating increasing vesicle stability. The microscopy and scattering data indicate the presence of two distinct nanoparticle families: uni-lamellar vesicles with average radius 90 Å and multi-lamellar vesicles with average radius 440 Å. In both families the inner core is occupied by the solvent. The presence of tamoxifen gives rise to a multi-lamellar structure of the lipid outer shell. It also induces a positive surface charge into the vesicles, repelling the positively charged chitosan molecules which therefore do not take part in nanoparticle formation.

  6. Structure and organization of phospholipid/polysaccharide nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Gerelli, Y; Bari, M T Di; Deriu, A [Dipartimento di Fisica and CNISM, Universita degli Studi di Parma and CRS SOFT, INFM-CNR (Italy); Cantu, L [Dipartimento di Chimica, Biochimica e Biotecnologie per la Medicina-LITA, Universita di Milano (Italy); Colombo, P; Como, C; Motta, S; Sonvico, F [Dipartimento Farmaceutico, Universita degli Studi di Parma (Italy); May, R [Institut Laue-Langevin, Grenoble (France)], E-mail: Antonio.Deriu@fis.unipr.it

    2008-03-12

    In recent years nanoparticles and microparticles composed of polymeric or lipid material have been proposed as drug carriers for improving the efficacy of encapsulated drugs. For the production of these systems different materials have been proposed, among them phospholipids and polysaccharides due to their biocompatibility, biodegradability, low cost and safety. We report here a morphological and structural investigation, performed using cryo-TEM, static light scattering and small angle neutron and x-ray scattering, on phospholipid/saccharide nanoparticles loaded with a lipophilic positively charged drug (tamoxifen citrate) used in breast cancer therapy. The lipid component was soybean lecithin; the saccharide one was chitosan that usually acts as an outer coating increasing vesicle stability. The microscopy and scattering data indicate the presence of two distinct nanoparticle families: uni-lamellar vesicles with average radius 90 A and multi-lamellar vesicles with average radius 440 A. In both families the inner core is occupied by the solvent. The presence of tamoxifen gives rise to a multi-lamellar structure of the lipid outer shell. It also induces a positive surface charge into the vesicles, repelling the positively charged chitosan molecules which therefore do not take part in nanoparticle formation.

  7. Metformin Decouples Phospholipid Metabolism in Breast Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Tim A D Smith

    Full Text Available The antidiabetic drug metformin, currently undergoing trials for cancer treatment, modulates lipid and glucose metabolism both crucial in phospholipid synthesis. Here the effect of treatment of breast tumour cells with metformin on phosphatidylcholine (PtdCho metabolism which plays a key role in membrane synthesis and intracellular signalling has been examined.MDA-MB-468, BT474 and SKBr3 breast cancer cell lines were treated with metformin and [3H-methyl]choline and [14C(U]glucose incorporation and lipid accumulation determined in the presence and absence of lipase inhibitors. Activities of choline kinase (CK, CTP:phosphocholine cytidylyl transferase (CCT and PtdCho-phospholipase C (PLC were also measured. [3H] Radiolabelled metabolites were determined using thin layer chromatography.Metformin-treated cells exhibited decreased formation of [3H]phosphocholine but increased accumulation of [3H]choline by PtdCho. CK and PLC activities were decreased and CCT activity increased by metformin-treatment. [14C] incorporation into fatty acids was decreased and into glycerol was increased in breast cancer cells treated with metformin incubated with [14C(U]glucose.This is the first study to show that treatment of breast cancer cells with metformin induces profound changes in phospholipid metabolism.

  8. [Some peculiarities of brain phospholipids in deep sea fishes].

    Science.gov (United States)

    Pomazanskaia, L F; Pravdina, N I; Chirkovskaia, E V

    1975-01-01

    Total phospholipids (PL) as well as the content of various phospholipid classes and their fatty acid composition have been investigated in the brain of mesopelagic and abyssal marine teleosts. These species were compared to shallow water ones. The brain of deep sea fishes was found to be very poor in PL as compared to the brain of mesopelagic ans surface water species. No differences concerning the brain PL content were revealed between the two last mentioned groups. The relative content of separate PL classes was very similar in all the species studied irrespectively of the depth of their habitat. Peculiarities were found in fatty acid composition of individual PL from deep sea species as compared to surface ones. The deeper the habitat, the lower the content of saturated fatty acids, especially of the stearic acid. The lowest content of saturated fatty acids, maximum level of polyenoic fatty acids as well as some peculiarities in the relative content of particular fatty acids were found in the brain of ultraabyssal (6, 000 m) Leucicorus sp. PMID:1217333

  9. Radiolabeling of liposomes and polymeric micelles with PET-isotopes

    International Nuclear Information System (INIS)

    This thesis is divided into three separate chapters that can be read independently. Chapter 1 is a general introduction, touching upon liposomes and polymeric micelles and radiolabeling with 18F and 64Cu. Chapter 2 and 3 address two separate research projects, each described below. A complete reference list is compiled in the end, immediately after the three chapters. This is followed by the supplementary information, divided into appropriate sections. Finally, the two first-authored manuscripts are attached as appendices. Chapter 1. The field of nanoparticulate drug delivery has been hailed as a revolution in modern therapeutics, especially in chemotherapy. A major reason is the ability of nanoparticles to accumulate in tumor tissue. Liposomes are the classic nanoparticle, consisting of a lipid membrane with an aqueous core. Polymeric micelles are made from amphiphilic detergent-like copolymers, that self-assemble in water. Therapy with nanoparticles is hampered by often poor tumor accumulation, combined with massive uptake by macrophages in the liver and spleen. For this reason, visualizing nanoparticle pharmacokinetics in-vivo is a valuable tool in the on-going research. Such visualization can be done by labeling with radio isotopes. Isotopes that emit positrons (PET-isotopes) can be detected by PET (positron emission tomography) technology, an accurate technique that has gained popularity in recent years. PET-isotopes of interest include 18F and 64Cu. In addition to being a research tool, radiolabeled nanoparticles hold promise as a radiopharmaceutical in themselves, as a means of imaging tumor tissue, aiding in diagnosis and surgery. Chapter 2. A method for labeling liposomes with 18F (97% positron decay, T = 110 min) was investigated. 18F is widely available, but is hampered by a short half-life only allowing up to 8 hours scans. 18F must be covalently attached to components of the liposome. By binding to a lipid, it can be stably lodged in the membrane. A

  10. Radiolabeling of liposomes and polymeric micelles with PET-isotopes

    Energy Technology Data Exchange (ETDEWEB)

    Ingemann Jensen, A.T.

    2013-06-01

    This thesis is divided into three separate chapters that can be read independently. Chapter 1 is a general introduction, touching upon liposomes and polymeric micelles and radiolabeling with 18F and 64Cu. Chapter 2 and 3 address two separate research projects, each described below. A complete reference list is compiled in the end, immediately after the three chapters. This is followed by the supplementary information, divided into appropriate sections. Finally, the two first-authored manuscripts are attached as appendices. Chapter 1. The field of nanoparticulate drug delivery has been hailed as a revolution in modern therapeutics, especially in chemotherapy. A major reason is the ability of nanoparticles to accumulate in tumor tissue. Liposomes are the classic nanoparticle, consisting of a lipid membrane with an aqueous core. Polymeric micelles are made from amphiphilic detergent-like copolymers, that self-assemble in water. Therapy with nanoparticles is hampered by often poor tumor accumulation, combined with massive uptake by macrophages in the liver and spleen. For this reason, visualizing nanoparticle pharmacokinetics in-vivo is a valuable tool in the on-going research. Such visualization can be done by labeling with radio isotopes. Isotopes that emit positrons (PET-isotopes) can be detected by PET (positron emission tomography) technology, an accurate technique that has gained popularity in recent years. PET-isotopes of interest include 18F and 64Cu. In addition to being a research tool, radiolabeled nanoparticles hold promise as a radiopharmaceutical in themselves, as a means of imaging tumor tissue, aiding in diagnosis and surgery. Chapter 2. A method for labeling liposomes with 18F (97% positron decay, T = 110 min) was investigated. 18F is widely available, but is hampered by a short half-life only allowing up to 8 hours scans. 18F must be covalently attached to components of the liposome. By binding to a lipid, it can be stably lodged in the membrane. A

  11. Phospholipid electrospun nanofibers: effect of solvents and co-axial processing on morphology and fiber diameter

    DEFF Research Database (Denmark)

    Jørgensen, Lars; Qvortrup, Klaus; Chronakis, Ioannis S.

    2015-01-01

    Asolectin phospholipid nano-microfibers were prepared using electrospinning processing. The asolectin fibers were studied by scanning electron microscopy, and the fiber morphology was found to be strongly dependent on the phospholipid concentration and the solvents used. The solvents studied were...

  12. A hybrid SAM phospholipid approach to fabricating a 'free' supported lipid bilayer

    DEFF Research Database (Denmark)

    Hughes, A.V.; Goldar, A.; Gerstenberg, M.C.;

    2002-01-01

    of phospholipid are separated from the silicon substrate and the lower layers by a hydration region approximately 30 A thick. This layer limits the tethering effect of the substrate such that the phospholipid molecules within the upper bilayer have significant freedom. This freedom is evidenced by the fact...

  13. An efficient hydrophilic interaction liquid chromatography separation of 7 phospholipid classes based on a diol column

    NARCIS (Netherlands)

    Zhu, C.; Dane, A.; Spijksma, G.; Wang, M.; Greef, J. van der; Luo, G.; Hankemeier, T.; Vreeken, R.J.

    2012-01-01

    A hydrophilic interaction liquid chromatography (HILIC) - ion trap mass spectrometry method was developed for separation of a wide range of phospholipids. A diol column which is often used with normal phase chromatography was adapted to separate different phospholipid classes in HILIC mode using a m

  14. Use of Magnetic Folate-Dextran-Retinoic Acid Micelles for Dual Targeting of Doxorubicin in Breast Cancer

    Directory of Open Access Journals (Sweden)

    J. Varshosaz

    2013-01-01

    Full Text Available Amphiphilic copolymer of folate-conjugated dextran/retinoic acid (FA/DEX-RA was self-assembled into micelles by direct dissolution method. Magnetic iron oxide nanoparticles (MNPs coated with oleic acid (OA were prepared by hydrothermal method and encapsulated within the micelles. Doxorubicin HCl was loaded in the magnetic micelles. The characteristics of the magnetic micelles were determined by Fourier transform infrared (FT-IR spectroscopy, thermogravimetric analysis (TGA, transmission electron microscopy (TEM, and vibrating sample magnetometer (VSM. The crystalline state of OA-coated MNPs and their heat capacity were analyzed by X-ray diffraction (XRD and differential scanning calorimetry (DSC methods, respectively. The iron content of magnetic micelles was determined using inductively coupled plasma optical emission spectrometry (ICP-OES. Bovine serum albumin (BSA was used to test the protein binding of magnetic micelles. The cytotoxicity of doxorubicin loaded magnetic micelles was studied on MCF-7 and MDA-MB-468 cells using MTT assay and their quantitative cellular uptake by fluorimetry method. TEM results showed the MNPs in the hydrophobic core of the micelles. TGA results confirmed the presence of OA and FA/DEX-RA copolymer on the surface of MNPs and micelles, respectively. The magnetic micelles showed no significant protein bonding and reduced the IC50 of the drug to about 10 times lower than the free drug.

  15. Enhancement of bioavailability by formulating rhEPO ionic complex with lysine into PEG-PLA micelle

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Yanan; Sun, Fengying; Wang, Dan; Zhang, Renyu [Jilin University, College of Life Science (China); Dou, Changlin; Liu, Wanhui; Sun, Kaoxiang, E-mail: sunkx@ytu.edu.cn [Yantai University, School of Pharmacy (China); Li, Youxin, E-mail: liyouxin@jlu.edu.cn [Jilin University, College of Life Science (China)

    2013-10-15

    A composite micelle of ionic complex encapsulated into poly(ethylene glycol)-poly(d,l-lactide) (PEG-PLA) di-block copolymeric micelles was used for protein drug delivery to improve its pharmacokinetic performance. In this study, recombinant human erythropoietin (rhEPO, as a model protein) was formulated with lysine into composite micelles at a diameter of 71.5 nm with narrow polydispersity indices (PDIs < 0.3). Only a trace amount of protein was in aggregate form. The zeta potential of the spherical micelles was ranging from -0.54 to 1.39 mv, and encapsulation efficiency is high (80 %). The stability of rhEPO was improved significantly in composite micelles in vitro. Pharmacokinetic studies in rats showed significant, enhanced plasma retention of the composite micelles in comparison with native rhEPO. Areas under curve (AUCs) of the rhEPO released from the composite micelles were 4.5- and 2.3-folds higher than those of the native rhEPO and rhEPO-loaded PEG-PLA micelle, respectively. In addition, the composite micelles exhibited good biocompatibility using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay with human embryonic kidney (HEK293T) cells. All these features are preferable for utilizing the composite micelles as a novel protein delivery system.

  16. Preparation and Characterization of Copolymer Micelles Formed by Poly(ethylene glycol)-Polylactide Block Copolymers as Novel Drug Carriers

    Institute of Scientific and Technical Information of China (English)

    姜维; 王运东; 甘泉; 张建铮; 赵秀文; 费维扬; 贝建中; 王身国

    2006-01-01

    Diblock copolymer poly(ethylene glycol) methyl ether-polylactide (MePEG-PLA) micelles were prepared by dialysis against water. Indomethacin (IMC) as a model drug was entrapped into the micelles by dialysis method. The critical micelle concentration (CMC) of the prepared micelles in distilled water investigated by fluorescence spectroscopy was 0.0051mg/mL which is lower than that of common low molecular weight surfactants. The diameters of MePEG-PLA micelles and IMC loaded MePEG-PLA micelles in a number-averaged scale measured by dynamic light scattering were 52.4 and 53.7 nm respectively. The observation with transmission electron microscope and scanning electron microscope showed that the appearance of MePEG-PLA micelles was in a spherical shape. The content of IMC incorporated in the core portion of the micelles was 18% (ω). The effects of the synthesis method of the copolymer on the polydispersity of the micelles and the yield of the micelles formation were discussed.

  17. Biodegradable polymeric micelle-encapsulated quercetin suppresses tumor growth and metastasis in both transgenic zebrafish and mouse models

    Science.gov (United States)

    Wu, Qinjie; Deng, Senyi; Li, Ling; Sun, Lu; Yang, Xi; Liu, Xinyu; Liu, Lei; Qian, Zhiyong; Wei, Yuquan; Gong, Changyang

    2013-11-01

    Quercetin (Que) loaded polymeric micelles were prepared to obtain an aqueous formulation of Que with enhanced anti-tumor and anti-metastasis activities. A simple solid dispersion method was used, and the obtained Que micelles had a small particle size (about 31 nm), high drug loading, and high encapsulation efficiency. Que micelles showed improved cellular uptake, an enhanced apoptosis induction effect, and stronger inhibitory effects on proliferation, migration, and invasion of 4T1 cells than free Que. The enhanced in vitro antiangiogenesis effects of Que micelles were proved by the results that Que micelles significantly suppressed proliferation, migration, invasion, and tube formation of human umbilical vein endothelial cells (HUVECs). Subsequently, transgenic zebrafish models were employed to investigate anti-tumor and anti-metastasis effects of Que micelles, in which stronger inhibitory effects of Que micelles were observed on embryonic angiogenesis, tumor-induced angiogenesis, tumor growth, and tumor metastasis. Furthermore, in a subcutaneous 4T1 tumor model, Que micelles were more effective in suppressing tumor growth and spontaneous pulmonary metastasis, and prolonging the survival of tumor-bearing mice. Besides, immunohistochemical and immunofluorescent assays suggested that tumors in the Que micelle-treated group showed more apoptosis, fewer microvessels, and fewer proliferation-positive cells. In conclusion, Que micelles, which are synthesized as an aqueous formulation of Que, possess enhanced anti-tumor and anti-metastasis activity, which can serve as potential candidates for cancer therapy.

  18. The role of ABCB4 gene in the pathogenesis of low phospholipid associated cholelithiasis%ABCB4基因在低磷脂相关性胆石病发病机制中的作用

    Institute of Scientific and Technical Information of China (English)

    李波

    2012-01-01

    人类肝细胞毛细胆管膜上ABCB4基因编码生成多药耐药蛋白3.该蛋白负责将磷脂从毛细胆管膜内侧转运到胆管腔,与胆汁酸盐微粒形成混合微粒以溶解胆固醇.当ABCB4基因缺陷时,胆汁中磷脂减少或缺乏,可使胆固醇呈过饱和状态促进胆固醇结晶形成.人类ABCB4基因突变导致的胆石病称为低磷脂相关性胆石病.其特征是青少年时出现明显胆石病症状和胆囊切除术后反复发作症状.低磷脂相关性胆石病是罕见的单基因突变的染色体隐性遗传病.突变的方式包括纯合子和杂合子突变,集中于在外显子编码区、内含子区域和5' UTR(untranslated region)区域.%The adenosine triphosphate-binding cassette subfamily member 4 (ABCB4) gene encodes multidrug resistance rotein 3 (MDR3),which is expressed on the cannalicular membranes of hepatocytes and translocates major phospholipids from the inner to the outer leaflet.Phospholipids are the major carrier and solvent of cholesterol,and in combination with bile salts form mixed micelles.Defects in ABCB4 function cause a low phospholipid content in bile,resulting in cholesterol supersaturation and crystal formation.Low phospholipid-associated cholelithiasis (LPAC) is characterized by the association of ABCB4 mutations and a low biliary phospholipid concentration,resulting in symptomatic gallstones starting before age 40 years,a high serum gamma glutamyl transferase (γ-GT) activity,intrahepatic microlithiasis,and recurrent biliary symptoms despite cholecystectomy.LPAC is an autosomal recessive condition caused by a rare single-gene mutation,commonly occurring in ABCB4,and can include homozygous and heterozygous point mutations in introns,coding exons,and 5 UTR regions.

  19. High intensity focused ultrasound responsive metallo-supramolecular block copolymer micelles.

    Science.gov (United States)

    Liang, Bo; Tong, Rui; Wang, Zhenhua; Guo, Shengwei; Xia, Hesheng

    2014-08-12

    The metal-supramolecular diblock copolymer containing mechano-labile bis(terpyridine)-Cu(II) complex linkage in the junction point was synthesized. These metal-ligand containing amphiphilic copolymers are able to self-assemble in aqueous solution to form spherical micelles with poly(propylene glycol) block forming the hydrophobic core. It is found that high intensity focused ultrasound can open the copolymer micelles and trigger the release of the payload in the micelle. The micellar properties and release kinetics of encapsulated guest molecule in response to ultrasound stimuli were investigated. The weak Cu(II)-terpyridine dynamic bond in the copolymer chain can be cleaved under ultrasound and thus leads to the disruption of the copolymer micelle and the release of loaded cargo. This study will open up a new way for the molecular design of ultrasound modulated drug delivery systems. PMID:25072274

  20. Effect of substitution on aniline in inducing growth of anionic micelles

    Indian Academy of Sciences (India)

    Gunjan Garg; V K Aswal; S K Kulshreshtha; P A Hassan

    2004-08-01

    Small-angle neutron scattering (SANS) measurements were carried out on sodium dodecyl sulfate (SDS) micelles in the presence of three different hydrophobic salts, i.e. aniline hydrochloride, -toluidine hydrochloride and -toluidine hydrochloride. All these salts induce a uniaxial growth of micelles to form prolate ellipsoidal structures. A progressive decrease in the surface charge of the micelles was observed with the addition of salts followed by a rapid growth of the micelles. The presence of a methyl substitution at the ortho position of aniline does not alter the growth behavior significantly. However, when the substitution is at meta position micellar growth is favored at lower salt concentration than that is observed for aniline. This can be explained in terms of the difference in the chemical environments of the substituents at the ortho and meta positions.

  1. The use of Reverse Micelles in Downstream Processing of Biotechnological Products

    CERN Document Server

    Lee, Kai Lun

    2011-01-01

    This paper aims to discuss the use of reverse micelles in downstream processing of biotechnological products. The interest in this technology is piqued firstly by various advantages of a liquid-liquid extraction process, among which are cost effectiveness, and ease of scaling up and implementing a continuous process for whole broth processing. The use of reverse micelles is thought to be among the most promising due to the high efficiency and selectivity being achieved in some systems. However, there are various issues that have impeded the widespread use of reverse micelles such as the identification and development of suitable surfactants and ligands; as well as difficulties in the back extraction process. These issues, as well as latest developments and applications of reverse micelles in downstream processing of biotechnological products will be discussed in this paper.

  2. Escape rate of muonium from micelles - as determined by competition kinetics

    International Nuclear Information System (INIS)

    A competition was established for the reaction of muonium atoms (Mu) between nitrate ions in water and benzene or styrene solubilized in micelles. The nitrate was 3.3 - times more efficient at inhibiting muonated free radical formation with benzene than with styrene as the radical-producing solute. Kinetic analysis of this system indicates that Mu emerges from micelles, on average, at least three times during its short (ns) lifetime, these being medium sized micelles carrying on average 3 benzene molecules. So Mu is certainly not trapped, nor even localized. Its escape rate is estimated to be ∼9x108 s-1, which is commensurate with an ordinary diffusion time. The results were obtained by determining the yield of muonated free radicals formed within the micelles using muon-level-crossing-resonance spectroscopy. (orig.)

  3. New Strategies for Constructing Polymeric Micelles and Hollow Spheres Via Self-Assembly

    Institute of Scientific and Technical Information of China (English)

    Ming Jiang

    2005-01-01

    @@ 1Introduction In recent years, self-assembly of block copolymers leading to micelles in selective solvents, which dissolve only one of the blocks, has developed rapidly because the micelles are very strong candidates for potential applications in advanced technologies. The micelles usually have core-shell structure which are connected by covalent bonds. Based on our long-term research on interpolymer complexation due to hydrogen bonding, where we noticed that the complexation often led to the formation of irregular aggregates, we succeeded recently in developing a series of new approaches to polymeric micelles and hollow spheres via specific intermolecular interactions. As in these approaches, a variety of polymers with interacting groups i.e. homopolymers, random copolymers, graft copolymers as well as low mass compounds (LMC), can be used as building blocks, our research strategies have substantially extended the field of self-assembly.

  4. Effect of concentration on surfactant micelle shapes--A molecular dynamics study

    Institute of Scientific and Technical Information of China (English)

    GAO Jian; GE Wei; LI Jinghai

    2005-01-01

    Many aspects of the behavior of surfactants have not been well understood due to the coupling of many different mechanisms. Computer simulation is, therefore, attractive in the sense that it can explore the effect of different mechanisms separately. In this paper, the shapes, structures and sizes of sodium dodecylbenzenesulfonate (SDBS) micelles under different concentrations in an oil/water mixture were studied via molecular dynamics (MD) simulations using a simplified atomistic model which basically maintains the hydrophile and lipophile properties of the surfactant molecules. Above the critical micellar concentration (cmc), surfactant molecules aggregate spontaneously to form a wide variety of assemblies, from spherical to rodlike, wormlike and bilayer micelles. Changes in their ratios of the principle moments of inertia (g1/g3, g2/g3) indicated the transition of micelle shapes at different concentrations. The aggregation number of micelle is found to have a power-law dependence on surfactant concentration.

  5. CD and 31P NMR studies of tachykinin and MSH neuropeptides in SDS and DPC micelles

    Science.gov (United States)

    Schneider, Sydney C.; Brown, Taylor C.; Gonzalez, Javier D.; Levonyak, Nicholas S.; Rush, Lydia A.; Cremeens, Matthew E.

    2016-02-01

    Secondary structural characteristics of substance P (SP), neurokinin A (NKA), neurokinin B (NKB), α-melanocyte stimulating hormone peptide (α-MSH), γ1-MSH, γ2-MSH, and melittin were evaluated with circular dichroism in phosphite buffer, DPC micelles, and SDS micelles. CD spectral properties of γ1-MSH and γ2-MSH as well as 31P NMR of DPC micelles with all the peptides are reported for the first time. Although, a trend in the neuropeptide/micelle CD data appears to show increased α-helix content for the tachykinin peptides (SP, NKA, NKB) and increased β-sheet content for the MSH peptides (α-MSH, γ1-MSH, γ2-MSH) with increasing peptide charge, the lack of perturbed 31P NMR signals for all neuropeptides could suggest that the reported antimicrobial activity of SP and α-MSH might not be related to a membrane disruption mode of action.

  6. Removal of Cr(VI from Aqueous Environments Using Micelle-Clay Adsorption

    Directory of Open Access Journals (Sweden)

    Mohannad Qurie

    2013-01-01

    Full Text Available Removal of Cr(VI from aqueous solutions under different conditions was investigated using either clay (montmorillonite or micelle-clay complex, the last obtained by adsorbing critical micelle concentration of octadecyltrimethylammonium ions onto montmorillonite. Batch experiments showed the effects of contact time, adsorbent dosage, and pH on the removal efficiency of Cr(VI from aqueous solutions. Langmuir adsorption isotherm fitted the experimental data giving significant results. Filtration experiments using columns filled with micelle-clay complex mixed with sand were performed to assess Cr(VI removal efficiency under continuous flow at different pH values. The micelle-clay complex used in this study was capable of removing Cr(VI from aqueous solutions without any prior acidification of the sample. Results demonstrated that the removal effectiveness reached nearly 100% when using optimal conditions for both batch and continuous flow techniques.

  7. Chitosan cushioned phospholipid membrane and its application in imaging ellipsometry based-biosensor

    International Nuclear Information System (INIS)

    Chitosan cushion can support the air stability of phospholipid membrane, but the problem of serum solubility of phospholipid membrane prevents it from use in serum detection applications. Poly (ethylene glycol) (PEG) shielding promises both stability and non-specific adsorption resistance for phospholipid membrane. An air stable phospholipid membrane microarray has been successfully fabricated on chitosan modified silicon wafer. We have demonstrated the potential application of PEGylated phospholipid membrane in imaging ellipsometry-based protein biosensor. Because of the strong resistance against non-specific adsorption of serum, antigens are immobilized onto the membrane surface through chemical activation and further bind their antibodies without using blocking agent. Taking advantage of the multiple and parallel reaction capabilities of microfluidic reactor system, we have assayed the binding by varying both the density of antigen on the membrane surface and the concentration of antibody in solution.

  8. Phospholipid Membrane Protection by Sugar Molecules during Dehydration-Insights into Molecular Mechanisms Using Scattering Techniques

    Energy Technology Data Exchange (ETDEWEB)

    Garvey, Christopher J.; Lenné, Thomas; Koster, Karen L.; Kent, Ben; Bryant, Gary [ANSTO; (USD); (ANU); (RMIT)

    2014-09-24

    Scattering techniques have played a key role in our understanding of the structure and function of phospholipid membranes. These techniques have been applied widely to study how different molecules (e.g., cholesterol) can affect phospholipid membrane structure. However, there has been much less attention paid to the effects of molecules that remain in the aqueous phase. One important example is the role played by small solutes, particularly sugars, in protecting phospholipid membranes during drying or slow freezing. In this paper, we present new results and a general methodology, which illustrate how contrast variation small angle neutron scattering (SANS) and synchrotron-based X-ray scattering (small angle (SAXS) and wide angle (WAXS)) can be used to quantitatively understand the interactions between solutes and phospholipids. Specifically, we show the assignment of lipid phases with synchrotron SAXS and explain how SANS reveals the exclusion of sugars from the aqueous region in the particular example of hexagonal II phases formed by phospholipids.

  9. Multifunctional polymeric micelles for delivery of drugs and siRNA.

    Science.gov (United States)

    Jhaveri, Aditi M; Torchilin, Vladimir P

    2014-01-01

    Polymeric micelles, self-assembling nano-constructs of amphiphilic copolymers with a core-shell structure have been used as versatile carriers for delivery of drugs as well as nucleic acids. They have gained immense popularity owing to a host of favorable properties including their capacity to effectively solubilize a variety of poorly soluble pharmaceutical agents, biocompatibility, longevity, high stability in vitro and in vivo and the ability to accumulate in pathological areas with compromised vasculature. Moreover, additional functions can be imparted to these micelles by engineering their surface with various ligands and cell-penetrating moieties to allow for specific targeting and intracellular accumulation, respectively, to load them with contrast agents to confer imaging capabilities, and incorporating stimuli-sensitive groups that allow drug release in response to small changes in the environment. Recently, there has been an increasing trend toward designing polymeric micelles which integrate a number of the above functions into a single carrier to give rise to "smart," multifunctional polymeric micelles. Such multifunctional micelles can be envisaged as key to improving the efficacy of current treatments which have seen a steady increase not only in hydrophobic small molecules, but also in biologics including therapeutic genes, antibodies and small interfering RNA (siRNA). The purpose of this review is to highlight recent advances in the development of multifunctional polymeric micelles specifically for delivery of drugs and siRNA. In spite of the tremendous potential of siRNA, its translation into clinics has been a significant challenge because of physiological barriers to its effective delivery and the lack of safe, effective and clinically suitable vehicles. To that end, we also discuss the potential and suitability of multifunctional polymeric micelles, including lipid-based micelles, as promising vehicles for both siRNA and drugs. PMID:24795633

  10. Multifunctional polymeric micelles for delivery of drugs and siRNA

    Directory of Open Access Journals (Sweden)

    Aditi M. Jhaveri

    2014-04-01

    Full Text Available Polymeric micelles, self-assembling nano-constructs of amphiphilic copolymers with a core-shell structure have been used as versatile carriers for delivery of drugs as well as nucleic acids. They have gained immense popularity owing to a host of favorable properties including their capacity to effectively solubilize a variety of poorly soluble pharmaceutical agents, biocompatibility, longevity, high stability in vitro and in vivo and the ability to accumulate in pathological areas with compromised vasculature. Moreover, additional functions can be imparted to these micelles by engineering their surface with various ligands and cell-penetrating moieties to allow for specific targeting and intracellular accumulation, respectively, to load them with contrast agents to confer imaging capabilities, and incorporating stimuli-sensitive groups that allow drug release in response to small changes in the environment. Recently, there has been an increasing trend towards designing polymeric micelles which integrate a number of the above functions into a single carrier to give rise to smart, multifunctional polymeric micelles. Such multifunctional micelles can be envisaged as key to improving the efficacy of current treatments which have seen a steady increase not only in hydrophobic small molecules, but also in biologics including therapeutic genes, antibodies and small interfering RNA (siRNA. The purpose of this review is to highlight recent advances in the development of multifunctional polymeric micelles specifically for delivery of drugs and siRNA. In spite of the tremendous potential of siRNA, its translation into clinics has been a significant challenge because of physiological barriers to its effective delivery and the lack of safe, effective and clinically suitable vehicles. To that end, we also discuss the potential and suitability of multifunctional polymeric micelles, including lipid-based micelles, as promising vehicles for both siRNA and drugs.

  11. Improvement of in vivo efficacy of recombinant human erythropoietin by encapsulation in PEG–PLA micelle

    Directory of Open Access Journals (Sweden)

    Shi YN

    2012-12-01

    Full Text Available Yanan Shi,1,2,* Wan Huang,1,* Rongcai Liang,1–3 Kaoxiang Sun,2,3 Fangxi Zhang,2,3 Wanhui Liu,2,3 Youxin Li1–31College of Life Science, Jilin University, Changchun, China; 2State Key Laboratory of Long-acting and Targeting Drug Delivery System, Luye Pharmaceutical Co, Ltd, Yantai, China; 3School of Pharmacy, Yantai University, Yantai, China*These authors contributed equally to this workAbstract: To improve the pharmacokinetics and stability of recombinant human erythropoietin (rhEPO, rhEPO was successfully formulated into poly(ethylene glycol–poly(d,l-lactide (PEG–PLA di-block copolymeric micelles at diameters ranging from 60 to 200 nm with narrow polydispersity indices (PDIs; PDI < 0.3 and trace amount of protein aggregation. The zeta potential of the spherical micelles was in the range of −3.78 to 4.65 mV and the highest encapsulation efficiency of rhEPO in the PEG–PLA micelles was about 80%. In vitro release profiles indicated that the stability of rhEPO in the micelles was improved significantly and only a trace amount of aggregate was found. Pharmacokinetic studies in rats showed highly enhanced plasma retention time of the rhEPO-loaded PEG-PLA micelles in comparison with the native rhEPO group. Increased hemoglobin concentrations were also found in the rat study. Native polyacrylamide gel electrophoresis results demonstrated that rhEPO was successfully encapsulated into the micelles, which was stable in phosphate buffered saline with different pHs and concentrations of NaCl. Therefore, PEG–PLA micelles can be a potential protein drug delivery system.Keywords: rhEPO, PEG–PLA micelle, in vitro, pharmacokinetics, pharmacodynamics

  12. From micelle to microemulsion: an investigation of structural changes using molecular dynamics

    OpenAIRE

    Amir Amani; Milad Amani

    2015-01-01

    Objective Although a huge number of experimental works may be observed in the literature for microemulsions, modelling reports on these nano-systems are rare. Additionally, no comprehensive work so far has detailed the changes occurring to a micellar droplet when oil molecules are introduced (i.e. obtaining microemulsions from micelles). This work aimed to simulate a micelle and a microemulsion system containing polysorbate 80 - as surfactant - and study the structural changes in the...

  13. Bioreducible unimolecular micelles based on amphiphilic multiarm hyperbranched copolymers for triggered drug release

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    A novel type of bioreducible amphiphilic multiarm hyperbranched copolymer (H40-star-PLA-SS-PEG) based on Boltorn H40 core,poly(L-lactide) (PLA) inner-shell,and poly(ethylene glycol) (PEG) outer-shell with disulfide-linkages between the hydrophobic and hydrophilic moieties was developed as unimolecular micelles for controlled drug release triggered by reduction.The obtained H40-star-PLA-SS-PEG was characterized in detail by nuclear magnetic resonance (NMR),Fourier transform infrared (FTIR),gel permeation chromatography (GPC),differential scanning calorimeter (DSC),and thermal gravimetric analysis (TGA).Transmission electron microscopy (TEM) and dynamic light scattering (DLS) analyses suggested that H40-star-PLA-SS-PEG formed stable unimolecular micelles in aqueous solution with an average diameter of 19 nm.Interestingly,these micelles aggregated into large particles rapidly in response to 10 mM dithiothreitol (DTT),most likely due to shedding of the hydrophilic PEG outer-shell through reductive cleavage of the disulfide bonds.As a hydrophobic anticancer model drug,doxorubicin (DOX) was encapsulated into these reductive unimolecular micelles.In vitro release studies revealed that under the reduction-stimulus,the detachment of PEG outer-shell in DOX-loaded micelles resulted in a rapid drug release.Flow cytometry and confocal laser scanning microscopy (CLSM) measurements indicated that these DOX-loaded micelles were easily internalized by living cells.Methyl tetrazolium (MTT) assay demonstrated a markedly enhanced drug efficacy of DOX-loaded H40-star-PLA-SS-PEG micelles as compared to free DOX.All of these results show that these bioreducible unimolecular micelles are promising carriers for the triggered intracellular delivery of hydrophobic anticancer drugs.

  14. A 502-Base Free-Solution Electrophoretic DNA Sequencing Method Using End-Attached Wormlike Micelles.

    Science.gov (United States)

    Istivan, Stephen B; Bishop, Daniel K; Jones, Angela L; Grosser, Shane T; Schneider, James W

    2015-11-17

    We demonstrate that the use of wormlike nonionic micelles as drag-tags in end-labeled free-solution electrophoresis ("micelle-ELFSE") provides single-base resolution of Sanger sequencing products up to 502 bases in length, a nearly 2-fold improvement over reported ELFSE separations. "CiEj" running buffers containing 48 mM C12E5, 6 mM C10E5, and 3 M urea (32.5 °C) form wormlike micelles that provide a drag equivalent to an uncharged DNA fragment with a length (α) of 509 bases (effective Rh = 27 nm). Runtime in a 40 cm capillary (30 kV) was 35 min for elution of all products down to the 26-base primer. We also show that smaller Triton X-100 micelles give a read length of 103 bases in a 4 min run, so that a combined analysis of the Sanger products using the two buffers in separate capillaries could be completed in 14 min for the full range of lengths. A van Deemter analysis shows that resolution is limited by diffusion-based peak broadening and wall adsorption. Effects of drag-tag polydispersity are not observed, despite the inherent polydispersity of the wormlike micelles. We ascribe this to a stochastic size-sampling process that occurs as micelle size fluctuates rapidly during the runtime. A theoretical model of the process suggests that fluctuations occur with a time scale less than 10 ms, consistent with the monomer exchange process in nonionic micelles. The CiEj buffer has a low viscosity (2.7 cP) and appears to be semidilute in micelle concentration. The large drag-tag size of the CiEj buffers leads to steric segregation of the DNA and tag for short fragments and attendant mobility shifts.

  15. Integral physicochemical properties of reverse micelles of sodium bis(2-ethylhexyl) sulfosuccinate (AOT)

    Science.gov (United States)

    Fedyaeva, O. A.; Shubenkova, E. G.; Poshelyuzhnaya, E. G.; Lutaeva, I. A.

    2016-08-01

    The effect the degree of hydration has on optical and electrophysical properties of water/AOT/ n-hexane system is studied. It is found that AOT reverse micelles form aggregates whose dimensions grow along with the degree of hydration and temperature. Aggregation enhances their electrical conductivity and shifts the UV spectrum of AOT reverse emulsions to the red region. Four states of water are found in the structure of AOT reverse micelles.

  16. A 502-Base Free-Solution Electrophoretic DNA Sequencing Method Using End-Attached Wormlike Micelles.

    Science.gov (United States)

    Istivan, Stephen B; Bishop, Daniel K; Jones, Angela L; Grosser, Shane T; Schneider, James W

    2015-11-17

    We demonstrate that the use of wormlike nonionic micelles as drag-tags in end-labeled free-solution electrophoresis ("micelle-ELFSE") provides single-base resolution of Sanger sequencing products up to 502 bases in length, a nearly 2-fold improvement over reported ELFSE separations. "CiEj" running buffers containing 48 mM C12E5, 6 mM C10E5, and 3 M urea (32.5 °C) form wormlike micelles that provide a drag equivalent to an uncharged DNA fragment with a length (α) of 509 bases (effective Rh = 27 nm). Runtime in a 40 cm capillary (30 kV) was 35 min for elution of all products down to the 26-base primer. We also show that smaller Triton X-100 micelles give a read length of 103 bases in a 4 min run, so that a combined analysis of the Sanger products using the two buffers in separate capillaries could be completed in 14 min for the full range of lengths. A van Deemter analysis shows that resolution is limited by diffusion-based peak broadening and wall adsorption. Effects of drag-tag polydispersity are not observed, despite the inherent polydispersity of the wormlike micelles. We ascribe this to a stochastic size-sampling process that occurs as micelle size fluctuates rapidly during the runtime. A theoretical model of the process suggests that fluctuations occur with a time scale less than 10 ms, consistent with the monomer exchange process in nonionic micelles. The CiEj buffer has a low viscosity (2.7 cP) and appears to be semidilute in micelle concentration. The large drag-tag size of the CiEj buffers leads to steric segregation of the DNA and tag for short fragments and attendant mobility shifts. PMID:26455271

  17. Phospholipid-modified polyethylenimine-based nanopreparations for siRNA–mediated gene silencing: Implications for transfection and the role of lipid components

    Science.gov (United States)

    Navarro, Gemma; Essex, Sean; Sawant, Rupa R.; Biswas, Swati; Nagesha, Dattatri; Sridhar, Srinivas; de ILarduya, Conchita Tros; Torchilin, Vladimir P.

    2013-01-01

    The clinical application of gene silencing mediated by small interfering RNA (siRNA) has been limited by the lack of efficient and safe carriers. Phospholipid modification of low molecular weight polyethylenimine (PEI 1.8 kDa) dramatically increased its gene down-regulation capacity while keeping cytotoxicity levels low. The silencing efficacy was highly dependent on the nature of the lipid grafted to PEI and the polymer/siRNA ratio employed. Phosphoethanolamine (DOPE and DPPE) and phosphocholine (PC) conjugation did not change the physicochemical properties and siRNA binding capacity of PEI complexes but had a large impact on their transfection and ability to downregulate Green Fluorescent Protein (GFP) expression (60%, 30% and 5% decrease of GFP expression respectively). We found that the micelle-forming structure of DOPE and DPPE-PEI dramatically changed PEI’s interaction with cell membranes and played a key role in promoting PEI 1.8 kDa transfection, completely ineffective in the absence of the lipid modification. PMID:23928214

  18. Evolution of phospholipid contents during the production of quark cheese from buttermilk.

    Science.gov (United States)

    Ferreiro, T; Martínez, S; Gayoso, L; Rodríguez-Otero, J L

    2016-06-01

    We report the evolution of phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidylcholine (PC), phosphatidylserine (PS), and sphingomyelin (SM) contents during the production of quark cheese from buttermilk by successive ultrafiltration concentration, enrichment with cream, concurrent homogenization and pasteurization, fermentative coagulation, and separation of quark from whey by further ultrafiltration. Buttermilk is richer than milk itself in phospholipids that afford desirable functional and technological properties, and is widely used in dairy products. To investigate how phospholipid content is affected by end-product production processes such as ultrafiltration, homogenization, pasteurization or coagulation, we measured the phospholipids at several stages of each of 5 industrial-scale quark cheese production runs. In each run, 10,000L of buttermilk was concentrated to half volume by ultrafiltration, enriched with cream, homogenized, pasteurized, inoculated with lactic acid bacteria, incubated to coagulation, and once more concentrated to half volume by ultrafiltration. Phospholipid contents were determined by HPLC with evaporative light scattering detection in the starting buttermilk, concentrated buttermilk, ultrafiltrate, cream-enriched concentrated buttermilk (both before and after concurrent homogenization and pasteurization), coagulate, and quark, and also in the rinsings obtained when the ultrafiltration equipment was washed following initial concentration. The average phospholipid content of buttermilk was approximately 5 times that of milk, and the phospholipid content of buttermilk fat 26 to 29 times that of milk fat. Although phospholipids did not cross ultrafiltration membranes, significant losses occurred during ultrafiltration (due to retention on the membranes) and during the homogenization and pasteurization process. During coagulation, however, phospholipid content rose, presumably as a consequence of the proliferation of the

  19. Evolution of phospholipid contents during the production of quark cheese from buttermilk.

    Science.gov (United States)

    Ferreiro, T; Martínez, S; Gayoso, L; Rodríguez-Otero, J L

    2016-06-01

    We report the evolution of phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidylcholine (PC), phosphatidylserine (PS), and sphingomyelin (SM) contents during the production of quark cheese from buttermilk by successive ultrafiltration concentration, enrichment with cream, concurrent homogenization and pasteurization, fermentative coagulation, and separation of quark from whey by further ultrafiltration. Buttermilk is richer than milk itself in phospholipids that afford desirable functional and technological properties, and is widely used in dairy products. To investigate how phospholipid content is affected by end-product production processes such as ultrafiltration, homogenization, pasteurization or coagulation, we measured the phospholipids at several stages of each of 5 industrial-scale quark cheese production runs. In each run, 10,000L of buttermilk was concentrated to half volume by ultrafiltration, enriched with cream, homogenized, pasteurized, inoculated with lactic acid bacteria, incubated to coagulation, and once more concentrated to half volume by ultrafiltration. Phospholipid contents were determined by HPLC with evaporative light scattering detection in the starting buttermilk, concentrated buttermilk, ultrafiltrate, cream-enriched concentrated buttermilk (both before and after concurrent homogenization and pasteurization), coagulate, and quark, and also in the rinsings obtained when the ultrafiltration equipment was washed following initial concentration. The average phospholipid content of buttermilk was approximately 5 times that of milk, and the phospholipid content of buttermilk fat 26 to 29 times that of milk fat. Although phospholipids did not cross ultrafiltration membranes, significant losses occurred during ultrafiltration (due to retention on the membranes) and during the homogenization and pasteurization process. During coagulation, however, phospholipid content rose, presumably as a consequence of the proliferation of the

  20. [Construction of biotin-modified polymeric micelles for pancreatic cancer targeted photodynamic therapy].

    Science.gov (United States)

    Deng, Chun-yue; Long, Ying-ying; Liu, Sha; Chen, Zhang-bao; Li, Chong

    2015-08-01

    In this study, we explored the feasibility of biotin-mediated modified polymeric micelles for pancreatic cancer targeted photodynamic therapy. Poly (ethylene glycol)-distearoyl phosphatidyl ethanolamine (mPEG2000-DSPE) served as the drug-loaded material, biotin-poly(ethylene glycol)-distearoyl phosphatidyl ethanolamine (Biotin-PEG3400-DSPE) as the functional material and the polymeric micelles were prepared by a thin-film hydration method. The targeting capability of micelles was investigated by cell uptake assay in vitro and fluorescence imaging in vivo and the amounts of Biotin-PEG-DSPE were optimized accordingly. Hypocrellin B (HB), a novel photosensitizer was then encapsulated in biotinylated polymeric micelles and the anti-tumor efficacy was evaluated systemically in vitro and in vivo. The results showed that micelles with 5 mol % Biotin-PEG-DSPE demonstrated the best targeting capability than those with 20 mol % or 0.5 mol % of corresponding materials. This formulation has a small particle size [mean diameter of (36.74 ± 2.16) nm] with a homogeneous distribution and high encapsulation efficiency (80.06 ± 0.19) %. The following pharmacodynamics assays showed that the biotinylated micelles significantly enhanced the cytotoxicity of HB against tumor cells in vitro and inhibited tumor growth in vivo, suggesting a promising potential of this formulation for treatment of pancreatic cancer, especially those poorly permeable, or insensitive to radiotherapy and chemotherapy. PMID:26669006

  1. Activity and Conformation of Yeast Alcohol Dehydrogenase (YADH) Entrapped in Reverse Micelles.

    Science.gov (United States)

    Das; Mozumdar; Maitra

    2000-10-15

    Yeast alcohol dehydrogenase (YADH) solubilized in reverse micelles of aerosol OT (i.e., AOT or sodium bis (2-ethyl hexyl) sulfosuccinate) in isooctane has been shown to be catalytically more active than that in aqueous buffer under optimum conditions of pH, temperature, and water content in reverse micelles. Studies of the secondary structure conformational changes of the enzyme in reverse micelles have been made from circular dichroism spectroscopy. It has been seen that the conformation of YADH in reverse micelles is extremely sensitive to pH, temperature, and water content. A comparison has been made between the catalytic activity of the enzyme and the alpha-helix content in the conformation and it has been observed that the enzyme is most active at the maximum alpha-helix content. While the beta-sheet content in the conformation of the entrapped enzyme was found to be dependent on the enzyme-micelle interface interaction, the alpha-helix and random coil conformations are governed by the degree of entrapment and the extent of rigidity provided by the micelle core to the enzyme structure. Copyright 2000 Academic Press.

  2. Dielectric relaxation spectroscopy shows a sparingly hydrated interface and low counterion mobility in triflate micelles.

    Science.gov (United States)

    Lima, Filipe S; Chaimovich, Hernan; Cuccovia, Iolanda M; Buchner, Richard

    2013-08-13

    The properties of ionic micelles are affected by the nature of the counterion. Specific ion effects can be dramatic, inducing even shape and phase changes in micellar solutions, transitions apparently related to micellar hydration and counterion binding at the micellar interface. Thus, determining the hydration and dynamics of ions in micellar systems capable of undergoing such transitions is a crucial step in understanding shape and phase changes. For cationic micelles, such transitions are common with large organic anions as counterions. Interestingly, however, phase separation also occurs for dodecyltrimethylammonium triflate (DTATf) micelles in the presence of sodium triflate (NaTf). Specific ion effects for micellar solutions of dodecyltrimethylammonium chloride (DTAC), bromide (DTAB), methanesulfonate (DTAMs), and triflate (DTATf) were studied with dielectric relaxation spectroscopy (DRS), a technique capable of monitoring hydration and counterion dynamics of micellar aggregates. In comparison to DTAB, DTAC, and DTAMs, DTATf micelles were found to be considerably less hydrated and showed reduced counterion mobility at the micellar interface. The obtained DTATf and DTAMs data support the reported central role of the anion's -CF3 moiety with respect to the properties of DTATf micelles. The reduced hydration observed for DTATf micelles was rationalized in terms of the higher packing of this surfactant compared to that of other DTA-based systems. The decreased mobility of Tf(-) anions condensed at the DTATf interface strongly suggests the insertion of Tf(-) in the micellar interface, which is apparently driven by the strong hydrophobicity of -CF3.

  3. Development of lycopene micelle and lycopene chylomicron and a comparison of bioavailability

    Science.gov (United States)

    Jyun Chen, Yi; Inbaraj, Baskaran Stephen; Shiau Pu, Yeong; Chen, Bing Huei

    2014-04-01

    The objectives of this study were to develop lycopene micelles and lycopene chylomicrons from tomato extracts for the enhancement and comparison of bioavailability. Lycopene micelles and chylomicrons were prepared by a microemulsion technique involving tomato extract, soybean oil, water, vitamin E and surfactant Tween 80 or lecithin in different proportions. The encapsulation efficiency of lycopene was 78% in micelles and 80% in chylomicrons, with shape being roughly spherical and mean particle size being 7.5 and 131.5 nm. A bioavailability study was conducted in rats by both gavage and i.v. administration, with oral bioavailability of lycopene, phytoene and phytofluene being 6.8, 4.3 and 3.1% in micelles and 9.5, 9.4 and 7.1% in chylomicrons, respectively. This outcome reveals higher lycopene bioavailability through incorporation into micelle or chylomicron systems. Both size and shape should be considered for oral bioavailability determination. For i.v. injection, lycopene micelles should be more important than lycopene chylomicrons for future clinical applications.

  4. Biodegradable micelles enhance the antiglioma activity of curcumin in vitro and in vivo.

    Science.gov (United States)

    Zheng, Songping; Gao, Xiang; Liu, Xiaoxiao; Yu, Ting; Zheng, Tianying; Wang, Yi; You, Chao

    2016-01-01

    Curcumin (Cur), a natural polyphenol of Curcuma longa, has been recently reported to possess antitumor activities. However, due to its poor aqueous solubility and low biological availability, the clinical application of Cur is quite limited. The encapsulation of hydrophobic drugs into nanoparticles is an effective way to improve their pharmaceutical activities. In this research, nanomicelles loaded with Cur were formulated by a self-assembly method with biodegradable monomethoxy poly(ethylene glycol)-poly(lactide) copolymers (MPEG-PLAs). After encapsulation, the cellular uptake was increased and Cur could be released from MPEG-PLA micelles in a sustained manner. The Cur-loaded MPEG-PLA micelles (Cur/MPEG-PLA micelles) exhibited an enhanced toxicity on C6 and U251 glioma cells and induced more apoptosis on C6 glioma cells compared with free Cur. Moreover, the therapy efficiency of Cur/MPEG-PLA micelles was evaluated at length on a nude mouse model bearing glioma. The Cur/MPEG-PLA micelles were more effective on suppressing tumor growth compared with free Cur, which indicated that Cur/MPEG-PLA micelles improved the antiglioma activity of Cur in vivo. The results of immunohistochemical and immunofluorescent analysis indicated that the induction of apoptosis, antiangiogenesis, and inhibition of cell proliferation may contribute to the improvement in antiglioma effects. Our data suggested that Cur/MPEG-PLA may have potential clinic applications in glioma therapy. PMID:27354801

  5. Influencing the structure of block copolymer micelles with small molecule additives

    Science.gov (United States)

    Robertson, Megan; Singh, Avantika; Cooksey, Tyler; Kidd, Bryce; Piemonte, Rachele; Wang, Shu; Mai Le, Kim; Madsen, Louis

    Amphiphilic block copolymer micelles in water are under broad exploration for drug delivery applications due to their high loading capacity and targeted drug delivery. We aim to understand the kinetic and thermodynamic processes that underlie the self-assembly of diblock copolymer micelle systems. The present work focuses on diblock copolymers containing poly(ethylene oxide) (a hydrophilic polymer) and polycaprolactone (a hydrophobic polymer), which spontaneously self-assemble into spherical micelles in water. Addition of a common good solvent (a co-solvent) for both of the constituting blocks, such as tetrahydrofuran (THF), reduces the interfacial tension at the core-corona interface. We are currently investigating the effect of this phenomenon on the micelle structural properties, using small-angle scattering and nuclear magnetic resonance. We have characterized the hydrodynamic radius, core radius, corona thickness, aggregation number, degree of swelling of the micelle core with the co-solvent, and unimer (free chain) concentration, as a function of the co-solvent concentration. Fundamental knowledge from these studies will inform design of drug delivery systems by allowing us to tailor micelle properties for optimal cargo loading.

  6. Thermosensitive PNIPAM-b-HTPB block copolymer micelles: molecular architectures and camptothecin drug release.

    Science.gov (United States)

    Luo, Yan-Ling; Yang, Xiao-Li; Xu, Feng; Chen, Ya-Shao; Zhang, Bin

    2014-02-01

    Two kinds of thermo-sensitive poly(N-isoproplacrylamide) (PNIPAM) block copolymers, AB4 four-armed star multiblock and linear triblock copolymers, were synthesized by ATRP with hydroxyl-terminated polybutadiene (HTPB) as central blocks, and characterization was performed by (1)H NMR, FT-IR and SEC. The multiblock copolymers could spontaneously assemble into more regular spherical core-shell nanoscale micelles than the linear triblock copolymer. The physicochemical properties were detected by a surface tension technique, nano particle analyzer, TEM, DLS and UV-vis measurements. The multiblock copolymer micelles had lower critical micelle concentration than the linear counterpart, TEM size from 100 to 120 nm and the hydrodynamic diameters below 150 nm. The micelles exhibited thermo-dependent size change, with low critical solution temperature about 33-35 °C. The characteristic parameters were affected by the composition ratios, length of PNIPAM blocks and molecular architectures. The camptothecin release demonstrated that the drug release was thermo-responsive, accompanied by the temperature-induced structural changes of the micelles. MTT assays were performed to evaluate the biocompatibility or cytotoxicity of the prepared copolymer micelles. PMID:24184534

  7. Phospholipides bio-sourcés riches en acides gras oméga 3 pour la formulation de liposomes

    OpenAIRE

    Bardeau, Tiphaine

    2015-01-01

    Liposomes, phospholipids vesicles, are colloidal systems used in search and different industrial fields (pharmaceutical, cosmetic, nutrition). Nevertheless their development face lack of phospholipid sources (soya and egg yolk). At the same time, industrial methods to extract phospholipids use organic solvents. In this context, the phospholipid extraction were studied using a green technology from new different sources in order to formulate liposomes. Oil mill and fishery by-products (seed ca...

  8. Brain-targeting study of stearic acid–grafted chitosan micelle drug-delivery system

    Directory of Open Access Journals (Sweden)

    Xie YT

    2012-06-01

    Full Text Available Yi-Ting Xie, Yong-Zhong Du, Hong Yuan, Fu-Qiang HuCollege of Pharmaceutical Sciences, Zhejiang University, Hangzhou, ChinaPurpose: Therapy for central nervous system disease is mainly restricted by the blood–brain barrier. A drug-delivery system is an effective approach to overcome this barrier. In this research, the potential of polymeric micelles for brain-targeting drug delivery was studied.Methods: Stearic acid–grafted chitosan (CS-SA was synthesized by hydrophobic modification of chitosan with stearic acid. The physicochemical characteristics of CS-SA micelles were investigated. bEnd.3 cells were chosen as model cells to evaluate the internalization ability and cytotoxicity of CS-SA micelles in vitro. Doxorubicin (DOX, as a model drug, was physically encapsulated in CS-SA micelles. The in vivo brain-targeting ability of CS-SA micelles was qualitatively and quantitatively studied by in vivo imaging and high-performance liquid chromatography analysis, respectively. The therapeutic effect of DOX-loaded micelles in vitro was performed on glioma C6 cells.Results: The critical micelle concentration of CS-SA micelles with 26.9% ± 1.08% amino substitute degree was 65 µg/mL. The diameter and surface potential of synthesized CS-SA micelles in aqueous solution was 22 ± 0.98 nm and 36.4 ± 0.71 mV, respectively. CS-SA micelles presented excellent cellular uptake ability on bEnd.3 cells, the IC50 of which was 237.6 ± 6.61 µg/mL. DOX-loaded micelles exhibited slow drug-release behavior, with a cumulative release up to 72% within 48 hours in vitro. The cytotoxicity of DOX-loaded CS-SA micelles against C6 was 2.664 ± 0.036 µg/mL, compared with 0.181 ± 0.066 µg/mL of DOX • HCl. In vivo imaging results indicated that CS-SA was able to transport rapidly across the blood–brain barrier and into the brain. A maximum DOX distribution in brain of 1.01%/g was observed 15 minutes after administration and maintained above 0.45%/g within 1 hour

  9. Biosynthesis of ether-phospholipids including plasmalogens, peroxisomes and human disease: new insights into an old problem

    NARCIS (Netherlands)

    R.J.A. Wanders; P. Brites

    2010-01-01

    Ether-phospholipids represent an important subclass of phospholipids in animal cell membranes characterized by the presence of an ether bond at the sn-I position and the enrichment of PUFAs at the sn-2 position. Of the different ether-phospholipids, plasmalogens are the most abundant form and their

  10. Marine Omega-3 Phospholipids: Metabolism and Biological Activities

    Directory of Open Access Journals (Sweden)

    Nils Hoem

    2012-11-01

    Full Text Available The biological activities of omega-3 fatty acids (n-3 FAs have been under extensive study for several decades. However, not much attention has been paid to differences of dietary forms, such as triglycerides (TGs versus ethyl esters or phospholipids (PLs. New innovative marine raw materials, like krill and fish by-products, present n-3 FAs mainly in the PL form. With their increasing availability, new evidence has emerged on n-3 PL biological activities and differences to n-3 TGs. In this review, we describe the recently discovered nutritional properties of n-3 PLs on different parameters of metabolic syndrome and highlight their different metabolic bioavailability in comparison to other dietary forms of n-3 FAs.

  11. Negatively cooperative binding of melittin to neutral phospholipid vesicles

    Science.gov (United States)

    Torrens, Francisco; Castellano, Gloria; Campos, Agustín; Abad, Concepción

    2007-05-01

    The association of basic amphipathic peptides to neutral phospholipid membranes is investigated in terms of binding and partition models. The binding of native and modified melittin to egg-yolk phosphatidylcholine vesicles is studied by steady-state fluorescence spectroscopy. The effect of the ionic strength shows an enhancement of the association as the ionic strength increases. After correction for electrostatic effects by the Gouy-Chapman theory, the melittin binding isotherms could be described by a partition model. In terms of conventional binding mechanisms, which do not take into account electrostatic effects, this would correspond to a negative cooperativity. A plausible way in which the interaction occurs is proposed, based on the calculated Hill coefficient.

  12. Enzyme catalysed production of phospholipids with modified fatty acid profile

    DEFF Research Database (Denmark)

    Vikbjerg, Anders Falk

    2006-01-01

    phospholipider blev udført i både ”packed bed”- og batchreaktorer med eller uden tilstedeværelse af solvent (organisk opløsningsmiddel). Under den praktiske udførelse af reaktionerne kan dannelsen af biprodukter, grundet sideløbende hydrolyse og acyl migrering, være et alvorligt problem. En grundig belysning af...... disse problemer og optimering af diverse reaktionssystemer blev udført i dette projekt. Til produktion i større skala er det praktisk at udføre reaktionerne i ”packed bed” reaktorer, da det tillader en kontinuerlig proces. Kontinuerlig proces i ”packed bed” reaktor blev dog vist at være vanskelig med et...

  13. Forms, Crosstalks, and the Role of Phospholipid Biosynthesis in Autophagy

    Directory of Open Access Journals (Sweden)

    Leanne Pereira

    2012-01-01

    Full Text Available Autophagy is a highly conserved cellular process occurring during periods of stress to ensure a cell's survival by recycling cytosolic constituents and making products that can be used in energy generation and other essential processes. Three major forms of autophagy exist according to the specific mechanism through which cytoplasmic material is transported to a lysosome. Chaperone-mediated autophagy is a highly selective form of autophagy that delivers specific proteins for lysosomal degradation. Microautophagy is a less selective form of autophagy that occurs through lysosomal membrane invaginations, forming tubes and directly engulfing cytoplasm. Finally, macroautophagy involves formation of new membrane bilayers (autophagosomes that engulf cytosolic material and deliver it to lysosomes. This review provides new insights on the crosstalks between different forms of autophagy and the significance of bilayer-forming phospholipid synthesis in autophagosomal membrane formation.

  14. Smoking and red blood cell phospholipid membrane fatty acids.

    Science.gov (United States)

    Murff, H J; Tindle, H A; Shrubsole, M J; Cai, Q; Smalley, W; Milne, G L; Swift, L L; Ness, R M; Zheng, W

    2016-09-01

    Smoking is associated with lower n-3 long chain polyunsaturated fatty acids (LCPUFA) concentrations; however, limited studies have accounted for dietary PUFA intake or whether tobacco dose or smoking duration influences this association. We measured red blood cell phospholipid (RBC) membrane concentrations of fatty acids in 126 current smokers, 311 former smokers, and 461 never smokers using gas liquid chromatography and tandem mass spectrometry. Smokers had lower RBC membrane percentages of total n-3 LCPUFAs compared to former smokers or never smokers (median percent: 5.46, [interquartile range (IQR) 4.52, 6.28] versus 6.39; [IQR: 5.18, 7.85] versus 6.59; [IQR 5.34, 8.01]) (psmoking and cigarettes per day were not associated with RBC membrane n-3 LCPUFA differences. Smoking is associated with lower n-3 LCPUFA RBC membrane percentages and this association was not influenced by diet or smoking dose or duration. PMID:27637337

  15. Microscopic methods in analysis of submicron phospholipid dispersions

    Directory of Open Access Journals (Sweden)

    Płaczek Marcin

    2016-03-01

    Full Text Available Microscopy belongs to the group of tests, used in pharmaceutical technology, that despite the lapse of time and the development of new analytical methods, still remain irreplaceable for the characterization of dispersed drug dosage forms (e.g., suspensions and emulsions. To obtain complete description of a specific drug formulation, such as parenteral colloidal products, a combination of different microscopic techniques is sometimes required. Electron microscopy methods are the most useful ones; however, even such basic methods as optical microscopy may be helpful for determination of some properties of a sample. The publication explicates the most popular microscopical techniques used nowadays for characterization of the morphology of nanoparticles suspended in pharmaceutical formulations; ad vantages and disadvantages of these methods are also discussed. Parenteral submicron formulations containing lecithin or a particular phospholipid were chosen as examples.

  16. Adsorption behavior of pH-dependent phytic acid micelles at the copper surface observed by Raman and electrochemistry

    Science.gov (United States)

    Shen, Shu; Du, Juan; Guo, Xiao-yu; Wen, Ying; Yang, Hai-Feng

    2015-02-01

    As heated at 90 °C, phytic acid (PA) molecules in the solution self-organized to form the PA micelles. The size of PA micelles could be tuned by varying pH of the solutions. The adsorption behavior of the different micelles at the copper surface and their corrosion inhibition mechanisms in 0.5 M H2SO4 solution were studied by using electrochemical impedance spectroscopy (EIS), potentiodynamic polarization and surface-enhanced Raman scattering (SERS) spectroscopy. Raman studies showed that the bigger micelles anchoring on the copper surface via P27sbnd O28, P43sbnd O42 and P35sbnd O36 groups, while the smaller PA micelles formed at pH 9 adsorbed at the surface through P35sbnd O36 group. The electrochemical measurements demonstrated that the copper modified with the smaller micelles presented the best inhibition efficiency in 0.5 M H2SO4 solution.

  17. Preparation and Evaluation of Poly(Ethylene Glycol)-Poly(Lactide) Micelles as Nanocarriers for Oral Delivery of Cyclosporine A

    Science.gov (United States)

    Zhang, Yanhui; Li, Xinru; Zhou, Yanxia; Wang, Xiaoning; Fan, Yating; Huang, Yanqing; Liu, Yan

    2010-06-01

    A series of monomethoxy poly(ethylene glycol)-poly(lactide) (mPEG-PLA) diblock copolymers were designed according to polymer-drug compatibility and synthesized, and mPEG-PLA micelle was fabricated and used as a nanocarrier for solubilization and oral delivery of Cyclosporine A (CyA). CyA was efficiently encapsulated into the micelles with nanoscaled diameter ranged from 60 to 96 nm with a narrow size distribution. The favorable stabilities of CyA-loaded polymeric micelles were observed in simulated gastric and intestinal fluids. The in vitro drug release investigation demonstrated that drug release was retarded by polymeric micelles. The enhanced intestinal absorption of CyA-loaded polymeric micelles, which was comparable to the commercial formulation of CyA (Sandimmun Neoral®), was found. These suggested that polymeric micelles might be an effective nanocarrier for solubilization of poorly soluble CyA and further improving oral absorption of the drug.

  18. Essential phospholipids in fatty liver: a scientific update

    Directory of Open Access Journals (Sweden)

    Gundermann KJ

    2016-05-01

    Full Text Available Karl-Josef Gundermann,1 Simon Gundermann,2 Marek Drozdzik,1 VG Mohan Prasad3 1Department of Pharmacology, Pomeranian Medical University, Szczecin, Poland; 2Department of Radiology, Hospital Hohenlind, Cologne, Germany; 3VGM Hospital Institute of Gastroenterology, Coimbatore, India Aim: Although essential phospholipids (EPL from soybean are often used in membrane-associated disorders and diseases, their high quality of purification and effects on prevalent liver diseases, especially on fatty liver diseases (FLDs of different origin, are still widely unknown and a matter of continuous active research. The aim of this article is to review, discuss, and summarize the available results of EPL in the treatment of FLD. Methods: Database research was carried out on Medline, Embase, Cochrane Library, country-specific journals, and follow-up literature citations for relevant hepatogastroenterological articles published between 1988 and 2014. We searched for and reviewed only those papers that indicated minimum extraction amount of 72% (3-sn-phosphatidylcholine from soybean as being necessary to treat patients with a considerable amount of 1,2-dilinoleoylphosphatidylcholine as a key component in EPL. Results: EPL has a well-established mode of action, therapeutic effectiveness, and lack of toxicity, which ensures clinically relevant efficacy-to-safety ratio. It influences membrane-dependent cellular functions and shows anti-inflammatory, antioxidant, antifibrogenic, antiapoptotic, membrane-protective, and lipid-regulating effects. Due to its positive effects on membrane composition and functions, it accelerates the improvement or normalization of subjective symptoms; pathological, clinical, and biochemical findings; hepatic imaging; and liver histology. It is justified to administer EPL together with other therapeutic measurements in the liver. Conclusion: Pharmacological and clinical results confirm the efficacy of EPL in the treatment of FLD. Keywords

  19. Identification of unusual phospholipid fatty acyl compositions of Acanthamoeba castellanii.

    Directory of Open Access Journals (Sweden)

    Marta Palusinska-Szysz

    Full Text Available Acanthamoeba are opportunistic protozoan pathogens that may lead to sight-threatening keratitis and fatal granulomatous encephalitis. The successful prognosis requires early diagnosis and differentiation of pathogenic Acanthamoeba followed by aggressive treatment regimen. The plasma membrane of Acanthamoeba consists of 25% phospholipids (PL. The presence of C20 and, recently reported, 28- and 30-carbon fatty acyl residues is characteristic of amoeba PL. A detailed knowledge about this unusual PL composition could help to differentiate Acanthamoeba from other parasites, e.g. bacteria and develop more efficient treatment strategies. Therefore, the detailed PL composition of Acanthamoeba castellanii was investigated by 31P nuclear magnetic resonance spectroscopy, thin-layer chromatography, gas chromatography, high performance liquid chromatography and liquid chromatography-mass spectrometry. Normal and reversed phase liquid chromatography coupled with mass spectrometric detection was used for detailed characterization of the fatty acyl composition of each detected PL. The most abundant fatty acyl residues in each PL class were octadecanoyl (18∶0, octadecenoyl (18∶1 Δ9 and hexadecanoyl (16∶0. However, some selected PLs contained also very long fatty acyl chains: the presence of 28- and 30-carbon fatty acyl residues was confirmed in phosphatidylethanolamine (PE, phosphatidylserine, phosphatidic acid and cardiolipin. The majority of these fatty acyl residues were also identified in PE that resulted in the following composition: 28∶1/20∶2, 30∶2/18∶1, 28∶0/20∶2, 30∶2/20∶4 and 30∶3/20∶3. The PL of amoebae are significantly different in comparison to other cells: we describe here for the first time unusual, very long chain fatty acids with Δ5-unsaturation (30∶35,21,24 and 30∶221,24 localized exclusively in specific phospholipid classes of A. castellanii protozoa that could serve as specific biomarkers for the presence of

  20. How can micelle systems be rebuilt by a heating process?

    Directory of Open Access Journals (Sweden)

    Silva-Filho MA

    2012-01-01

    Full Text Available Miguel Adelino da Silva-Filho1, Scheyla Daniela Vieira da Silva Siqueira1, Larissa Bandeira Freire1, Ivonete Batista de Araújo2, Káttya Gyselle de Holanda e Silva2, Aldo da Cunha Medeiros3, Irami Araújo-Filho3, Anselmo Gomes de Oliveira4, Eryvaldo Sócrates Tabosa do Egito21Dispersed Systems Laboratory, Federal University of Rio Grande do Norte (UFRN, Natal, Rio Grande do Norte, Brazil; 2Department of Pharmacy, UFRN, Natal, Rio Grande do Norte, Brazil; 3Department of Experimental Surgery, UFRN, Natal, Rio Grande do Norte, Brazil; 4Department of Drugs and Medicines, College of Pharmaceutical Sciences (UNESP, Araraquara, São Paulo, BrazilAbstract: The aim of this work was to evaluate how an aqueous micellar system containing Amphotericin B (AmB and sodium deoxycholate (DOC can be rebuilt after heating treatment. Also, a review of the literature on the physicochemical and biological properties of this new system was conducted. Heated (AmB-DOC-H and unheated (AmB-DOC micelles were then diluted at four different concentrations (50 mg · L-1, 5 mg · L-1, 0.5 mg · L-1, and 0.05 mg · L-1 to perform physicochemical studies and a pharmacotoxicity assay, in which two cell models were used for the in vitro experiments: red blood cells (RBC from human donors and Candida parapsilosis (Cp. While potassium (K+ and hemoglobin leakage from RBC were the parameters used to evaluate acute and chronic toxicity, respectively, the efficacy of AmB-DOC and AmB-DOC-H were assessed by K+ leakage and cell survival rate from Cp. The spectral study revealed a slight change in the AmB-DOC aggregate peak from 327 nm to 323 nm, which is the peak for AmB-DOC-H. Although AmB-DOC and AmB-DOC-H exhibited different behavior for hemoglobin leakage, AmB-DOC produced higher leakage than AmB-DOC-H at high concentrations (from 5 mg ·L-1. For K+ leakage, both AmB-DOC and AmB-DOC-H showed a similar profile for both cell models, RBC and Cp (P < 0.05. AmB-DOC-H and AmB-DOC also

  1. Polymeric Micelles for Delivery of Poorly Soluble Drugs: Preparation and Anticancer Activity In Vitro of Paclitaxel Incorporated into Mixed Micelles Based on Poly(ethylene Glycol)-Lipid Conjugate and Positively Charged Lipids

    OpenAIRE

    Wang, Junping; MONGAYT, DIMITRY; Torchilin, Vladimir P.

    2005-01-01

    Paclitaxel-loaded mixed polymeric micelles consisting of poly(ethylene glycol)-distearoyl phosphoethanolamine conjugates (PEG-PE), solid triglycerides (ST), and cationic Lipofectin® lipids (LL) have been prepared. Micelles with the optimized composition (PEG-PE/ST/LL/paclitaxel = 12/12/2/1 by weight) had an average micelle size of about 100 nm, and zeta-potential of about 26 mV. Micelles were stable and did not release paclitaxel when stored at 4°C in the darkness (just 2.9% of paclitaxel hav...

  2. Study on Osmotic Pressure and Liquid-Liquid Equilibria for Micelle, Colloid and Microemulsion Systems by Yukawa Potential

    Institute of Scientific and Technical Information of China (English)

    FU,Dong(付东); LU,Jiu-Fang(陆九芳); WU,Wei(吴畏); Li,Yi-Gui(李以圭)

    2004-01-01

    An equation of state (EOS) was established to study the osmotic pressure and liquid-liquid equilibria for micelle,colloid and microemulsion systems. The Carnahan-Starling equation was used for the hard sphere repulsion. The Yukawa potential was used to describe both the attractive dispersion and the double-layer repulsion. By using the established EOS, the osmotic pressures for charged colloid, uncharged micelle, uncharged and weakly charged microemuslion, the phase equilibria for uncharged micelle and charged colloid systems were studied.

  3. Theranostic reduction-sensitive gemcitabine prodrug micelles for near-infrared imaging and pancreatic cancer therapy

    Science.gov (United States)

    Han, Haijie; Wang, Haibo; Chen, Yangjun; Li, Zuhong; Wang, Yin; Jin, Qiao; Ji, Jian

    2015-12-01

    A biodegradable and reduction-cleavable gemcitabine (GEM) polymeric prodrug with in vivo near-infrared (NIR) imaging ability was reported. This theranostic GEM prodrug PEG-b-[PLA-co-PMAC-graft-(IR820-co-GEM)] was synthesized by ring-opening polymerization and ``click'' reaction. The as-prepared reduction-sensitive prodrug could self-assemble into prodrug micelles in aqueous solution confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). In vitro drug release studies showed that these prodrug micelles were able to release GEM in an intracellular-mimicking reductive environment. These prodrug micelles could be effectively internalized by BxPC-3 pancreatic cancer cells, which were observed by confocal laser scanning microscopy (CLSM). Meanwhile, a methyl thiazolyl tetrazolium (MTT) assay demonstrated that this prodrug exhibited high cytotoxicity against BxPC-3 cells. The in vivo whole-animal near-infrared (NIR) imaging results showed that these prodrug micelles could be effectively accumulated in tumor tissue and had a longer blood circulation time than IR820-COOH. The endogenous reduction-sensitive gemcitabine prodrug micelles with the in vivo NIR imaging ability might have great potential in image-guided pancreatic cancer therapy.A biodegradable and reduction-cleavable gemcitabine (GEM) polymeric prodrug with in vivo near-infrared (NIR) imaging ability was reported. This theranostic GEM prodrug PEG-b-[PLA-co-PMAC-graft-(IR820-co-GEM)] was synthesized by ring-opening polymerization and ``click'' reaction. The as-prepared reduction-sensitive prodrug could self-assemble into prodrug micelles in aqueous solution confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). In vitro drug release studies showed that these prodrug micelles were able to release GEM in an intracellular-mimicking reductive environment. These prodrug micelles could be effectively internalized by BxPC-3 pancreatic cancer cells, which

  4. A folate-integrated magnetic polymer micelle for MRI and dual targeted drug delivery

    Science.gov (United States)

    Ao, Lijiao; Wang, Bi; Liu, Peng; Huang, Liang; Yue, Caixia; Gao, Duyang; Wu, Chunlei; Su, Wu

    2014-08-01

    This paper devotes a novel micellar structure for cancer theranostics by incorporating magnetic and therapeutic functionalities into a natural sourced targeting polymer vehicle. Heparin-folic acid micelles taking advantage of both excellent loading capability and cancer targeting ability have been employed to simultaneously incorporate superparamagnetic iron oxide nanoparticles (SPIONs) and doxorubicin through an ultrasonication-assisted microemulsion method. In this system, folic acids not only take the responsibility of micelle construction, but also facilitate cellular uptake due to their specific reorganization by MCF-7 cells over-expressing folate receptors. The obtained micelles exhibit good colloidal stability, a high magnetic content, considerable drug loading and sustained in vitro drug release. These clustered SPIONs exhibited high r2 relaxivity (243.65 mM-1 s-1) and further served as efficient probes for MR imaging. Notably, the transport efficiency of these micelles could be significantly improved under an external magnetic field, owing to their quick magnetic response. As a result, the as-proposed micelle shows great potential in multimodal theranostics, including active targeting, MRI diagnosis and drug delivery.This paper devotes a novel micellar structure for cancer theranostics by incorporating magnetic and therapeutic functionalities into a natural sourced targeting polymer vehicle. Heparin-folic acid micelles taking advantage of both excellent loading capability and cancer targeting ability have been employed to simultaneously incorporate superparamagnetic iron oxide nanoparticles (SPIONs) and doxorubicin through an ultrasonication-assisted microemulsion method. In this system, folic acids not only take the responsibility of micelle construction, but also facilitate cellular uptake due to their specific reorganization by MCF-7 cells over-expressing folate receptors. The obtained micelles exhibit good colloidal stability, a high magnetic content

  5. pH-Responsive Poly(ethylene glycol)/Poly(L-lactide) Supramolecular Micelles Based on Host-Guest Interaction.

    Science.gov (United States)

    Zhang, Zhe; Lv, Qiang; Gao, Xiaoye; Chen, Li; Cao, Yue; Yu, Shuangjiang; He, Chaoliang; Chen, Xuesi

    2015-04-29

    pH-responsive supramolecular amphiphilic micelles based on benzimidazole-terminated poly(ethylene glycol) (PEG-BM) and β-cyclodextrin-modified poly(L-lactide) (CD-PLLA) were developed by exploiting the host-guest interaction between benzimidazole (BM) and β-cyclodextrin (β-CD). The dissociation of the supramolecular micelles was triggered in acidic environments. An antineoplastic drug, doxorubicin (DOX), was loaded into the supramolecular micelles as a model drug. The release of DOX from the supramolecular micelles was clearly accelerated as the pH was reduced from 7.4 to 5.5. The DOX-loaded PEG-BM/CD-PLLA supramolecular micelles displayed an enhanced intracellular drug-release rate in HepG2 cells compared to the pH-insensitive DOX-loaded PEG-b-PLLA counterpart. After intravenous injection into nude mice bearing HepG2 xenografts by the tail vein, the DOX-loaded supramolecular micelles exhibited significantly higher tumor inhibition efficacy and reduced systemic toxicity compared to free DOX. Furthermore, the DOX-loaded supramolecular micelles showed a blood clearance rate markedly lower than that of free DOX and comparable to that of the DOX-loaded PEG-b-PLLA micelles after intravenous injection into rats. Therefore, the pH-responsive PEG-BM/CD-PLLA supramolecular micelles hold potential as a smart nanocarrier for anticancer drug delivery. PMID:25856564

  6. Self-assembled micelles of amphiphilic poly(L-phenylalanine-b-poly(L-serine polypeptides for tumor-targeted delivery

    Directory of Open Access Journals (Sweden)

    Zhao ZM

    2014-12-01

    Full Text Available Ziming Zhao,1,2,* Yu Wang,1,2,* Jin Han,1,2 Keli Wang,1 Dan Yang,1,2 Yihua Yang,1,2 Qian Du,1,2 Yuanjian Song,3 Xiaoxing Yin1,2 1Department of Pharmacy, 2Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, 3Department of Basic Medical Sciences, Xuzhou Medical College, Xuzhou, People’s Republic of China *These authors contributed equally to this work Abstract: The aim of this work was to design, synthesize, and characterize self-assembled micelles based on polypeptides as a potential antitumor drug carrier. Amphiphilic poly(L-phenylalanine-b-poly(L-serine (PFS polypeptides were obtained through the polymerization of N-carboxyanhydride. As a novel hydrophilic segment, poly(L-serine was utilized to enhance tumor targeting due to a large demand of tumors for serine. PFS could self-assemble into micelles with an average diameter of 110–240 nm and a slightly negative charge. PFS polypeptides adopted random coil in pH 7.4 phosphate-buffered saline and could partly transform to a-helix induced by trifluoroethanol. PFS micelles with a low critical micelle concentration of 4.0 µg mL-1 were stable in pH 5–9 buffers and serum albumin solution. PFS micelles had a loading capacity of 3.8% for coumarin-6 and exhibited a sustained drug release. Coumarin-6 loaded rhodamine B isothiocyanate-labeled PFS micelles were incubated with Huh-7 tumor cells to study the correlation between drugs and carriers during endocytosis. The uptake of drugs was consistent with the micelles, illustrating that the intracellular transport of drugs highly depended on the micelles. PFS micelles diffused in whole cytoplasm while coumarin-6 assumed localized distribution, suggesting that the micelles could release the loaded drugs in particular areas. The internalization mechanism of PFS micelles was involved with clathrin-mediated endocytosis and macropinocytosis. Excess serine inhibited the uptake of PFS micelles, which demonstrated that serine receptors played

  7. Preparation, Characterization and Evaluation of α-Tocopherol Succinate-Modified Dextran Micelles as Potential Drug Carriers

    Directory of Open Access Journals (Sweden)

    Jingmou Yu

    2015-09-01

    Full Text Available In the present study, α-tocopherol succinate (TOS conjugated dextran (Dex-TOS was synthesized and characterized by fourier transform infrared (FT-IR spectroscopy, 1H nuclear magnetic resonance (1H NMR, dynamic light scattering (DLS and fluorescence spectroscopy. Dex-TOS could form nanoscaled micelles in aqueous medium. The critical micelle concentration (CMC is 0.0034 mg/mL. Doxorubicin (Dox was selected as a model drug. Dox-loaded Dex-TOS (Dex-TOS/Dox micelles were prepared by a dialysis method. The size of Dex-TOS/Dox micelles increased from 295 to 325 nm with the Dox-loading content increasing from 4.21% to 8.12%. The Dex-TOS/Dox micelles were almost spherical in shape, as determined by transmission electron microscopy (TEM. In vitro release demonstrated that Dox release from the micelles was in a sustained manner for up to 96 h. The cellular uptake of Dex-TOS/Dox micelles in human nasopharyngeal epidermoid carcinoma (KB cells is an endocytic process determined by confocal laser scanning microscopy (CLSM. Moreover, Dex-TOS/Dox micelles exhibited comparable cytotoxicity in contrast with doxorubicin hydrochloride. These results suggested that Dex-TOS micelles could be a promising carrier for drug delivery.

  8. Synthesis and Characterization of Folate-Targeted Dextran/Retinoic Acid Micelles for Doxorubicin Delivery in Acute Leukemia

    Directory of Open Access Journals (Sweden)

    J. Varshosaz

    2014-01-01

    Full Text Available Folate and retinoic acid grafted/dextran (FA-RA/DEX copolymers with different molecular weight of DEX were synthesized using carbonyldiimidazole and dimethylaminopyridine for targeted delivery of doxorubicin (DOX in acute myelogenous leukemia (AML. The copolymers structure was confirmed by 1H NMR and FTIR. Critical micelle concentration (CMC of each copolymer was determined using pyrene as a fluorescent probe. DOX was loaded in micelles by the direct dissolution method. Physical properties of micelles, including particle size, zeta potential, drug loading efficiency, and drug release profiles, were examined. The orientation of the folate ligand on the surface of the micelles was studied by X-ray photoelectron spectroscopy (XPS technique. The cytotoxicity of micelles loaded with DOX at different concentrations was studied in KG1 cells using MTT assay and their cellular uptake by flow cytometry technique. FTIR and 1H NMR spectra confirmed successful production of the targeted micelles and XPS spectra showed the surface orientation of folate. R15D10F7 copolymer produced micelles with particle size of 82.86 nm, polydispersity index of 0.3, zeta potential of −4.68 mV, drug loading efficiency of 96%, and release efficiency of 63%. DOX loaded in folate-targeted micelles of RA/DEX was more toxic than that in nontargeted micelles and free drug and seems promising in reducing drug resistance in AML.

  9. Synthesis and Characterization of a Micelle-Based pH Nanosensor with an Unprecedented Broad Measurement Range

    DEFF Research Database (Denmark)

    Ek, Pramod Kumar; Feldborg, Lise N.; Almdal, Kristoffer;

    2013-01-01

    A new cross-linked micelle pH nanosensor design was investigated. The nanosensor synthesis was based on self-assembly of an amphiphilic triblock copolymer, poly(ethylene glycol)-b-poly(2-amino ethyl methacrylate)-b-poly(coumarin methacrylate) (PEG-b-PAEMA-b-PCMA), which was synthesized by isolated...... macroinitiator atom transfer radical polymerization. Micelles were formed by PEG-b-PAEMA-b-PCMA self-assembly in water, giving micelles with an average diameter of 45 nm. The PCMA core was employed to utilize coumarin-based photoinduced cross-linking in the core of the micelles, which was performed by UV...

  10. Flip-flop of phospholipids in proteoliposomes reconstituted from detergent extract of chloroplast membranes: kinetics and phospholipid specificity.

    Directory of Open Access Journals (Sweden)

    Archita Rajasekharan

    Full Text Available Eukaryotic cells are compartmentalized into distinct sub-cellular organelles by lipid bilayers, which are known to be involved in numerous cellular processes. The wide repertoire of lipids, synthesized in the biogenic membranes like the endoplasmic reticulum and bacterial cytoplasmic membranes are initially localized in the cytosolic leaflet and some of these lipids have to be translocated to the exoplasmic leaflet for membrane biogenesis and uniform growth. It is known that phospholipid (PL translocation in biogenic membranes is mediated by specific membrane proteins which occur in a rapid, bi-directional fashion without metabolic energy requirement and with no specificity to PL head group. A recent study reported the existence of biogenic membrane flippases in plants and that the mechanism of plant membrane biogenesis was similar to that found in animals. In this study, we demonstrate for the first time ATP independent and ATP dependent flippase activity in chloroplast membranes of plants. For this, we generated proteoliposomes from Triton X-100 extract of intact chloroplast, envelope membrane and thylakoid isolated from spinach leaves and assayed for flippase activity using fluorescent labeled phospholipids. Half-life time of flipping was found to be 6 ± 1 min. We also show that: (a intact chloroplast and envelope membrane reconstituted proteoliposomes can flip fluorescent labeled analogs of phosphatidylcholine in ATP independent manner, (b envelope membrane and thylakoid reconstituted proteoliposomes can flip phosphatidylglycerol in ATP dependent manner, (c Biogenic membrane ATP independent PC flipping activity is protein mediated and (d the kinetics of PC translocation gets affected differently upon treatment with protease and protein modifying reagents.

  11. Serum Phospholipid Docosahexaenoic Acid Is Inversely Associated with Arterial Stiffness in Metabolically Healthy Men

    Science.gov (United States)

    Lee, Mi-Hyang; Kwon, Nayeon; Yoon, So Ra

    2016-01-01

    We hypothesized that lower proportion of serum phospholipid docosahexaenoic acid (DHA) is inversely associated with increased cardiovascular risk and vascular function in metabolically healthy men. To elucidate it, we first compared serum phospholipid free fatty acid (FA) compositions and cardiovascular risk parameters between healthy men (n = 499) and male patients with coronary artery disease (CAD, n = 111) (30-69 years) without metabolic syndrome, and then further-analyzed the association of serum phospholipid DHA composition with arterial stiffness expressed by brachial-ankle pulse wave velocity (ba-PWV) in metabolically healthy men. Basic parameters, lipid profiles, fasting glycemic status, adiponectin, high sensitivity C-reactive protein (hs-CRP) and LDL particle size, and serum phospholipid FA compositions were significantly different between the two subject groups. Serum phospholipid DHA was highly correlated with most of long-chain FAs. Metabolically healthy men were subdivided into tertile groups according to serum phospholipid DHA proportion: lower ( 3.235%). Fasting glucose, insulin resistance, hs-CRP and ba-PWVs were significantly higher and adiponectin and LDL particle size were significantly lower in the lower-DHA group than the higher-DHA group after adjusted for confounding factors. In metabolically healthy men, multiple stepwise regression analysis revealed that serum phospholipid DHA mainly contributed to arterial stiffness (β′-coefficients = -0.127, p = 0.006) together with age, systolic blood pressure, triglyceride (r = 0.548, p = 0.023). Lower proportion of serum phospholipid DHA was associated with increased cardiovascular risk and arterial stiffness in metabolically healthy men. It suggests that maintaining higher proportion of serum phospholipid DHA may be beneficial for reducing cardiovascular risk including arterial stiffness in metabolically healthy men. PMID:27482523

  12. Analysis of the phospholipid profile of metaphase II mouse oocytes undergoing vitrification.

    Directory of Open Access Journals (Sweden)

    Jaehun Jung

    Full Text Available Oocyte freezing confers thermal and chemical stress upon the oolemma and various other intracellular structures due to the formation of ice crystals. The lipid profiles of oocytes and embryos are closely associated with both, the degrees of their membrane fluidity, as well as the degree of chilling and freezing injuries that may occur during cryopreservation. In spite of the importance of lipids in the process of cryopreservation, the phospholipid status in oocytes and embryos before and after freezing has not been investigated. In this study, we employed mass spectrometric analysis to examine if vitrification has an effect on the phospholipid profiles of mouse oocytes. Freshly prepared metaphase II mouse oocytes were vitrified using copper grids and stored in liquid nitrogen for 2 weeks. Fresh and vitrified-warmed oocytes were subjected to phospholipid extraction procedure. Mass spectrometric analyses revealed that multiple species of phospholipids are reduced in vitrified-warmed oocytes. LIFT analyses identified 31 underexpressed and 5 overexpressed phospholipids in vitrified mouse oocytes. The intensities of phosphatidylinositol (PI {18∶2/16∶0} [M-H]- and phosphatidylglycerol (PG {14∶0/18∶2} [M-H]- were decreased the most with fold changes of 30.5 and 19.1 in negative ion mode, respectively. Several sphingomyelins (SM including SM {d38∶3} [M+H]+ and SM {d34∶0} [M+K]+ were decreased significantly in positive ion mode. Overall, the declining trend of multiple phospholipids demonstrates that vitrification has a marked effect on phospholipid profiles of oocytes. These results show that the identified phospholipids can be used as potential biomarkers of oocyte undergoing vitrification and will allow for the development of strategies to preserve phospholipids during oocyte cryopreservation.

  13. Ecotoxicological assessment of the micelle encapsulator F-500.

    Science.gov (United States)

    Pane, Luigi; Mariottini, Gian Luigi; Giacco, Elisabetta

    2015-08-01

    Surfactants are synthetic chemicals utilized as detergents and cleaning products or as dispersants and emulsifiers to face water pollution. In spite of this, due to their wide diffusion, surfactants can induce water and soil pollution, notably in developed countries, and can be toxic to organisms. Taking into account that the assessment of new compounds is mandatory in the European Union, in this research the ecotoxicity of fire-fighting micelle encapsulator F-500, newly utilized as dispersant in seawaters polluted with oil dumping, was evaluated. The assessment was carried out on a battery of test-organisms (freshwater algae, crustaceans, and larval fish; seawater algae, crustaceans, and bivalves; soil earthworms, and seeds) as well as on cultured cells (L-929 mouse fibroblasts), which were exposed to F-500 concentrations. According to the toxicity thresholds provided by GESAMP, F-500 resulted to be slightly or moderately toxic to all test-organisms, excluding the freshwater alga Pseudokirchneriella subcapitata that suffered highly toxic effects with IC50 values ranging from 0.21 to 0.49mg/L. The IC50 for mouse fibroblasts was 5.41µg/L after 24h treatment. PMID:25938697

  14. Different Types of Charged-Inverse Micelles in Nonpolar Media.

    Science.gov (United States)

    Prasad, Manoj; Strubbe, Filip; Beunis, Filip; Neyts, Kristiaan

    2016-06-14

    Over the last few years, the electrodynamics of charged inverse micelles (CIMs) in nonpolar liquids and the generation mechanism and properties of newly generated CIMs have been studied extensively for the model system of polyisobutylene succinimide in dodecane. However, the newly generated CIMs, which accumulate at the electrodes when a continuous voltage is applied, behave differently compared to the regular CIMs present in equilibrium in the absence of a field. In this work, we use transient current measurements to investigate the behavior of the newly generated CIMs when the field is reduced to zero or reversed. We demonstrate that the newly generated CIMs do not participate in the diffuse double layer near the electrode formed by the regular CIMs but form an interface layer at the electrode surface. A fraction of the newly generated negative CIMs can be released from this interface layer when the field there becomes zero. The findings of this study provide a better understanding of fundamental processes in nonpolar liquids and are relevant for applications such as electronic ink displays and liquid toner printing. PMID:27231768

  15. Ultrafast energy transfer in water-AOT reverse micelles.

    Science.gov (United States)

    Cringus, Dan; Bakulin, Artem; Lindner, Jörg; Vöhringer, Peter; Pshenichnikov, Maxim S; Wiersma, Douwe A

    2007-12-27

    A spectroscopic investigation of the vibrational dynamics of water in a geometrically confined environment is presented. Reverse micelles of the ternary microemulsion H2O/AOT/n-octane (AOT = bis-2-ethylhexyl sulfosuccinate or aerosol-OT) with diameters ranging from 1 to 10 nm are used as a model system for nanoscopic water droplets surrounded by a soft-matter boundary. Femtosecond nonlinear infrared spectroscopy in the OH-stretching region of H2O fully confirms the core/shell model, in which the entrapped water molecules partition onto two molecular subensembles: a bulk-like water core and a hydration layer near the ionic surfactant headgroups. These two distinct water species display different relaxation kinetics, as they do not exchange vibrational energy. The observed spectrotemporal ultrafast response exhibits a local character, indicating that the spatial confinement influences approximately one molecular layer located near the water-amphiphile boundary. The core of the encapsulated water droplet is similar in its spectroscopic properties to the bulk phase of liquid water, i.e., it does not display any true confinement effects such as droplet-size-dependent vibrational lifetimes or rotational correlation times. Unlike in bulk water, no intermolecular transfer of OH-stretching quanta occurs among the interfacial water molecules or from the hydration shell to the bulk-like core, indicating that the hydrogen bond network near the H2O/AOT interface is strongly disrupted. PMID:18047308

  16. Crystalline free energies of micelles of diblock copolymer solutions

    CERN Document Server

    D'Adamo, Giuseppe; 10.1063/1.3509391

    2012-01-01

    We report a characterization of the relative stability and structural behavior of various micellar crystals of an athermal model of AB-diblock copolymers in solution. We adopt a previously devel- oped coarse-graining representation of the chains which maps each copolymer on a soft dumbbell. Thanks to this strong reduction of degrees of freedom, we are able to investigate large aggregated systems, and for a specific length ratio of the blocks f = MA/(MA + MB) = 0.6, to locate the order-disorder transition of the system of micelles. Above the transition, mechanical and thermal properties are found to depend on the number of particles per lattice site in the simulation box, and the application of a recent methodology for multiple occupancy crystals (B.M. Mladek et al., Phys. Rev. Lett. 99, 235702 (2007)) is necessary to correctly define the equilibrium state. Within this scheme we have performed free energy calculations at two reduced density {\\rho}/{\\rho}\\ast = 4,5 and for several cubic structures as FCC,BCC,A1...

  17. Zwitterionic-Modified Starch-Based Stealth Micelles for Prolonging Circulation Time and Reducing Macrophage Response.

    Science.gov (United States)

    Ye, Lei; Zhang, Yabin; Yang, Boguang; Zhou, Xin; Li, Junjie; Qin, Zhihui; Dong, Dianyu; Cui, Yuanlu; Yao, Fanglian

    2016-02-01

    Over the last few decades, nanoparticles have been emerging as useful means to improve the therapeutic efficacy of drug delivery and medical diagnoses. However, the heterogeneity and complexity of blood as a medium is a fundamental problem; large amounts of protein can be adsorbed onto the surface of nanoparticles and cause their rapid clearance before reaching their target sites, resulting in the failure of drug delivery. To overcome this challenge, we present a rationally designed starch derivative (SB-ST-OC) with both a superhydrophilic moiety of zwitterionic sulfobetaine (SB) and a hydrophobic segment of octane (OC) as functional groups, which can self-assemble into "stealth" micelles (SSO micelles). The superhydrophilic SB kept the micelles stable against aggregation in complex media and imbued them with "stealth" properties, eventually extending their circulation time in blood. In stability and hemolysis tests the SSO micelles showed excellent protein resistance properties and hemocompatibility. Moreover, a phagocytosis test and cytokine secretion assay confirmed that the SSO micelles had less potential to trigger the activation of macrophages and were more suitable as a drug delivery candidate in vivo. On the basis of these results, doxorubicin (DOX), a hydrophobic drug, was used to investigate the potential application of this novel starch derivative in vivo. The results of the pharmacokinetic study showed that the values of the plasma area under the concentration curve (AUC) and elimination half-life (T1/2) of the SSO micelles were higher than those of micelles without SB modifications. In conclusion, the combination of excellent protein resistance, lower macrophage activation, and longer circulation time in vivo makes this synthesized novel starch derivative a promising candidate as a hydrophobic drug carrier for long-term circulation in vivo.

  18. Dependence of micelle size and shape on detergent alkyl chain length and head group.

    Directory of Open Access Journals (Sweden)

    Ryan C Oliver

    Full Text Available Micelle-forming detergents provide an amphipathic environment that can mimic lipid bilayers and are important tools for solubilizing membrane proteins for functional and structural investigations in vitro. However, the formation of a soluble protein-detergent complex (PDC currently relies on empirical screening of detergents, and a stable and functional PDC is often not obtained. To provide a foundation for systematic comparisons between the properties of the detergent micelle and the resulting PDC, a comprehensive set of detergents commonly used for membrane protein studies are systematically investigated. Using small-angle X-ray scattering (SAXS, micelle shapes and sizes are determined for phosphocholines with 10, 12, and 14 alkyl carbons, glucosides with 8, 9, and 10 alkyl carbons, maltosides with 8, 10, and 12 alkyl carbons, and lysophosphatidyl glycerols with 14 and 16 alkyl carbons. The SAXS profiles are well described by two-component ellipsoid models, with an electron rich outer shell corresponding to the detergent head groups and a less electron dense hydrophobic core composed of the alkyl chains. The minor axis of the elliptical micelle core from these models is constrained by the length of the alkyl chain, and increases by 1.2-1.5 Å per carbon addition to the alkyl chain. The major elliptical axis also increases with chain length; however, the ellipticity remains approximately constant for each detergent series. In addition, the aggregation number of these detergents increases by ∼16 monomers per micelle for each alkyl carbon added. The data provide a comprehensive view of the determinants of micelle shape and size and provide a baseline for correlating micelle properties with protein-detergent interactions.

  19. pH-sensitive micelles for targeted drug delivery prepared using a novel membrane contactor method.

    Science.gov (United States)

    Laouini, Abdallah; Koutroumanis, Konstantinos P; Charcosset, Catherine; Georgiadou, Stella; Fessi, Hatem; Holdich, Richard G; Vladisavljević, Goran T

    2013-09-25

    A novel membrane contactor method was used to produce size-controlled poly(ethylene glycol)-b-polycaprolactone (PEG-PCL) copolymer micelles composed of diblock copolymers with different average molecular weights, Mn (9200 or 10,400 Da) and hydrophilic fractions, f (0.67 or 0.59). By injecting 570 L m(-2) h(-1) of the organic phase (a 1 mg mL(-1) solution of PEG-PCL in tetrahydrofuran) through a microengineered nickel membrane with a hexagonal pore array and 200 μm pore spacing into deionized water agitated at 700 rpm, the micelle size linearly increased from 92 nm for a 5-μm pore size to 165 nm for a 40-μm pore size. The micelle size was finely tuned by the agitation rate, transmembrane flux and aqueous to organic phase ratio. An encapsulation efficiency of 89% and a drug loading of ~75% (w/w) were achieved when a hydrophobic drug (vitamin E) was entrapped within the micelles, as determined by ultracentrifugation method. The drug-loaded micelles had a mean size of 146 ± 7 nm, a polydispersity index of 0.09 ± 0.01, and a ζ potential of -19.5 ± 0.2 mV. When drug-loaded micelles where stored for 50 h, a pH sensitive drug release was achieved and a maximum amount of vitamin E (23%) was released at the pH of 1.9. When a pH-sensitive hydrazone bond was incorporated between PEG and PCL blocks, no significant change in micelle size was observed at the same micellization conditions.

  20. Pharmacokinetics and antitumor efficacy of micelles assembled from multiarmed amphiphilic copolymers with drug conjugates in comparison with drug-encapsulated micelles.

    Science.gov (United States)

    Luo, Xiaoming; Chen, Maohua; Zhang, Yun; Chen, Zhoujiang; Li, Xiaohong

    2016-01-01

    The premature drug release and structural dissociation before reaching pathological sites have posed major challenges for self-assembled micelles. To address these challenges, star-shaped amphiphilic copolymers derived from 4-armed poly(ethylene glycol) (PEG) were proposed for chemical conjugation of chemotherapeutic drugs and assembly into drug-conjugated micelles (DCM) with reductive sensitivity. The current study aimed to elucidate the in vitro and in vivo performance of DCM and a comparison with conventional drug-encapsulated micelles (DEM) was initially launched. DEM carriers were constructed with a similar structure to DCM from 4-armed PEG, and disulfide linkages were located between the hydrophilic and hydrophobic segments. Both DCM and DEM had an average size of around 130 nm, camptothecin (CPT) loadings of around 7.7% and critical micelle concentrations of around 0.95 μg/ml. Compared with DEM, DCM showed a lower initial drug release, a lower sensitivity of drug release to glutathione, and a higher structural stability after incubation with human serum albumin (HSA). The CPT derivatives (CPT-SH) released from DCM indicated cytotoxicities similar to CPT and remained a higher lactone stability than CPT in the presence of HSA. DCM showed slightly higher cytotoxicities to 4T1 cells and significantly lower cytotoxicities to normal cells than DEM. Pharmacokinetic analyses after intravenous administration of DCM indicated around 2.65 folds higher AUC0-∞, 2.66 folds lower clearance, and 1.87 folds higher tumor accumulation than those of DEM. In addition to a less disturbance to hematological and biochemical parameters and a lower acute toxicity to small intestines, DCM showed more significant tumor suppression efficacy and less tumor metastasis to lungs than DEM. It is suggested that DCM could overcome the limitation of conventional micelles by alleviating the premature drug release during blood circulation, relieving the systemic toxicity and promoting the

  1. Biophysical studies of cholesterol in unsaturated phospholipid model membranes

    Science.gov (United States)

    Williams, Justin Adam

    Cellular membranes contain a staggering diversity of lipids. The lipids are heterogeneously distributed to create regions, or domains, whose physical properties differ from the bulk membrane and play an essential role in modulating the function of resident proteins. Many basic questions pertaining to the formation of these lateral assemblies remain. This research employs model membranes of well-defined composition to focus on the potential role of polyunsaturated fatty acids (PUFAs) and their interaction with cholesterol (chol) in restructuring the membrane environment. Omega-3 (n-3) PUFAs are the main bioactive components of fish oil, whose consumption alleviates a variety of health problems by a molecular mechanism that is unclear. We hypothesize that the incorporation of PUFAs into membrane lipids and the effect they have on molecular organization may be, in part, responsible. Chol is a major constituent in the plasma membrane of mammals. It determines the arrangement and collective properties of neighboring lipids, driving the formation of domains via differential affinity for different lipids. The molecular organization of 1-[2H31]palmitoyl-2-eicosapentaenoylphosphatidylcholine (PEPC-d31) and 1-[2H31]palmitoyl-2-docosahexaenoylphosphatidylcholine (PDPC-d31) in membranes with sphingomyelin (SM) and chol (1:1:1 mol) was compared by solid-state 2H NMR spectroscopy. Eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids are the two major n-3 PUFAs found in fish oil, while PEPC-d31 and PDPC-d31 are phospholipids containing the respective PUFAs at the sn-2 position and a perdeuterated palmitic acid at the sn-1 position. Analysis of spectra recorded as a function of temperature indicates that in both cases, formation of PUFA-rich (less ordered) and SM-rich (more ordered) domains occurred. A surprisingly substantial proportion of PUFA was found to infiltrate the more ordered domain. There was almost twice as much DHA (65%) as EPA (30%). The implication is that n-3

  2. Amphiphilic Copolymeric Micelles for Doxorubicin and Curcumin Co-Delivery to Reverse Multidrug Resistance in Breast Cancer.

    Science.gov (United States)

    Lv, Li; Qiu, Kaifeng; Yu, Xiaoxia; Chen, Chuxiong; Qin, Fengchao; Shi, Yonghui; Ou, Jiebin; Zhang, Tao; Zhu, Hua; Wu, Junyan; Liu, Chunxia; Li, Guocheng

    2016-05-01

    Development of multidrug resistance against chemotherapeutic drugs is one of the major obstacles to successful cancer therapy in the clinic. Thus far, amphiphilic polymeric micelles and chemosensitizers have been used to overcome multidrug resistance in cancer. The goals of this study were to prepare poly(ethylene glycol)-bock-poly(lactide) (PEG(2k)-PLA(5k)) micelles for co-delivery of the chemotherapeutic drug doxorubicin (DOX) with a chemosensitizer curcumin (CUR), investigate the potential of the dual drug-loaded micelles ((DOX+CUR)-Micelles) to reverse multidrug resistance, and explore the underlying mechanisms. (DOX + CUR)-Micelles were prepared using an emulsion solvent evaporation method. The cellular uptake, drug efflux, down-regulation of P-glycoprotein expression and inhibition of ATP activity of (DOX+ CUR)-Micelles were studied in drug-resistant MCF-7/ADR cells. In vitro analyses demonstrated that (DOX + CUR)-Micelles were superior to free DOX, free drug combination (DOX + CUR), and DOX-loaded micelles in inhibiting proliferation of MCF-7/ADR cells. This effect of (DOX + CUR)-Micelles was partially attributable to their highest cellular uptake, lowest efflux rate of DOX, and strongest effects on down-regulation of P-glycoprotein and inhibition of ATP activity. Additionally, (DOX+CUR)-Micelles showed increased tumor accumulation and strong inhibitory effect on tumor growth in the xenograft model of drug-resistant MCF-7/ADR cells compared to that of other drug formulations. These results indicate that (DOX + CUR)-Micelles display potential for application in the therapy of drug-resistant breast carcinoma. PMID:27305819

  3. Biochemical characterization of the interactions between doxorubicin and lipidic GM1 micelles with or without paclitaxel loading

    Science.gov (United States)

    Leonhard, Victoria; Alasino, Roxana V; Bianco, Ismael D; Garro, Ariel G; Heredia, Valeria; Beltramo, Dante M

    2015-01-01

    Doxorubicin (Dox) is an anthracycline anticancer drug with high water solubility, whose use is limited primarily due to significant side effects. In this study it is shown that Dox interacts with monosialoglycosphingolipid (GM1) ganglioside micelles primarily through hydrophobic interactions independent of pH and ionic strength. In addition, Dox can be incorporated even into GM1 micelles already containing highly hydrophobic paclitaxel (Ptx). However, it was not possible to incorporate Ptx into Dox-containing GM1 micelles, suggesting that Dox could be occupying a more external position in the micelles. This result is in agreement with a higher hydrolysis of Dox than of Ptx when micelles were incubated at alkaline pH. The loading of Dox into GM1 micelles was observed over a broad range of temperature (4°C–55°C). Furthermore, Dox-loaded micelles were stable in aqueous solutions exhibiting no aggregation or precipitation for up to 2 months when kept at 4°C–25°C and even after freeze–thawing cycles. Upon exposure to blood components, Dox-containing micelles were observed to interact with human serum albumin. However, the amount of human serum albumin that ended up being associated to the micelles was inversely related to the amount of Dox, suggesting that both could share their binding sites. In vitro studies on Hep2 cells showed that the cellular uptake and cytotoxic activity of Dox and Ptx from the micellar complexes were similar to those of the free form of these drugs, even when the micelle was covered with albumin. These results support the idea of the existence of different nano-domains in a single micelle and the fact that this micellar model could be used as a platform for loading and delivering hydrophobic and hydrophilic active pharmaceutical ingredients. PMID:26005348

  4. NMR characterization of membrane protein-detergent micelle solutions by use of microcoil equipment.

    Science.gov (United States)

    Stanczak, Pawel; Horst, Reto; Serrano, Pedro; Wüthrich, Kurt

    2009-12-30

    Using microcoil NMR technology, the uniformly (2)H,(15)N-labeled integral membrane protein OmpX, and the phosphocholine derivative detergent Fos-10 (n-decylphosphocholine), we investigated solutions of mixed protein-detergent micelles to determine the influence of the detergent concentration on the NMR spectra of the protein. In a first step, we identified key parameters that influence the composition of the micelle solutions, which resulted in a new protocol for the preparation of well-defined concentrated protein solutions. This led to the observation that high-quality 2D [(15)N,(1)H]-transverse relaxation-optimized spectroscopy (TROSY) spectra of OmpX reconstituted in mixed micelles with Fos-10 were obtained only in a limited range of detergent concentrations. Outside of this range from about 90-180 mM, we observed a significant decrease of the average peak intensity. Relaxation-optimized NMR measurements of the rotational and translational diffusion coefficients of the OmpX/Fos-10 mixed micelles, D(r) and D(t), respectively, then showed that the stoichiometry and the effective hydrodynamic radius of the protein-containing micelles are not significantly affected by high Fos-10 concentrations and that the deterioration of NMR spectra is due to the increased viscosity at high detergent concentrations. The paper thus provides a basis for refined guidelines on the preparation of integral membrane proteins for structural studies.

  5. Preparation and Characterization of a pH-Responsive Core Cross-linked Polymer Micelle

    Energy Technology Data Exchange (ETDEWEB)

    Kousaka, Shouta; Sugahara, Makoto; Endo, Tatsuya; Yusa, Shin-ichi, E-mail: yusa@eng.u-hyogo.ac.jp [Department of Materials Science and Chemistry, Graduate School of Engineering, University of Hyogo, 2167 Shosha, Himeji, Hyogo 671-2280 (Japan)

    2011-01-01

    Poly(ethylene glycol)-b-poly(2-(diethylamino) ethyl methacrylate-co-2-cinnamoyl-oxyethyl acrylate) (PEG-b-P(DEA/CEA)) was prepared by reversible addition-fragmentation chain transfer (RAFT) controlled radical polymerization. pH-responsive association behaviour of PEG-b-P(DEA/CEA) in 0.1 M NaCl was characterized by dynamic light scattering (DLS). As solution pH is increased from an acidic pH, the hydrodynamic radius (R{sub h}) increases, indicative of the polymer micelle formation. The formation of a micelle was also supported by static light scattering (SLS) data. The cinnamoyl groups in the core of the polymer micelle undergo photodimerization, yielding cross-links between polymer chains. The core of the polymer micelle was fixed, which was confirmed by DLS, SLS, and small angle X-ray scattering (SAXS) techniques. When pH is decreased to 3, R{sub h} of the core cross-linked (CCL) polymer micelle slightly increases due to the protonation of the DEA unit in the cross-linked core. The reversible pH-induced swelling and shrinking behaviour can be observed.

  6. Comparative evaluation of polymersome versus micelle structures as vehicles for the controlled release of drugs

    International Nuclear Information System (INIS)

    Di-block copolymers composed of two biocompatible polymers, poly(ethylene glycol) and poly(d,l-lactide), were synthesized by ring-opening polymerization for the preparation of doxorubicin-loaded self-assembled nanostructures, including polymeric vesicles (polymersomes) and micelles. The capability and stability of the nanostructures prepared for the controlled release of DOX are discussed in this paper. The in vitro drug release at 37 °C was evaluated up to 6 days at pH 7.4 and 5.5 and in the presence of 50 % FBS. The cellular uptake and cytotoxicity effect of both formulations were also evaluated in the MCF-7 cell line. The SEM and AFM images confirmed the hollow spherical structure of the polymersomes and the solid round structures of the micelles. The TEM results also revealed the uniformity in size and shape of the drug-loaded micelle and polymersome nanostructures. The DOX-loaded micelles and polymersomes presented efficient anticancer performance, as verified by flow cytometry and MTT assay tests. The most important finding of this study is that the prepared nanopolymersomes presented significant increases in the doxorubicin encapsulation efficiency and the stability of the formulation in comparison with the micelle formulation. In vitro studies revealed that polymersomes may be stable in the blood circulation and meet the requirements for an effective drug delivery system

  7. Effect of A Long Chain Carboxylate Acid on Sodium Dodecyl Sulfate Micelle Structure: A SANS Study

    Science.gov (United States)

    Patriati, Arum; Giri Rachman Putra, Edy; Seok Seong, Baek

    2010-01-01

    The effect of a different hydrocarbon chain length of carboxylate acid, i.e. dodecanoic acid, CH3(CH)10COOH or lauric acid and hexadecanoic acid, CH3(CH2)14COOH or palmitic acid as a co-surfactant in the 0.3 M sodium dedecyl sulfate, SDS micellar solution has been studied using small angle neutron scattering (SANS). The present of lauric acid has induced the SDS structural micelles. The ellipsoid micelles structures changed significantly in length (major axis) from 22.6 Å to 37.1 Å at a fixed minor axis of 16.7 Å in the present of 0.005 M to 0.1 M lauric acid. Nevertheless, this effect did not occur in the present of palmitic acid with the same concentration range. The present of palmitic acid molecules performed insignificant effect on the SDS micelles growth where the major axis of the micelle was elongated from 22.9 Å to 25.3 Å only. It showed that the appropriate hydrocarbon chain length between surfactant and co-surfactant molecules emerged as one of the determining factors in forming a mixed micelles structure.

  8. Polymeric micelles for apoptosis-targeted optical imaging of cancer and intraoperative surgical guidance.

    Directory of Open Access Journals (Sweden)

    Hyunah Cho

    Full Text Available In a two-step strategy, an intraperitoneal (IP injection of poly(ethylene glycol-block-poly(ε-caprolactone (PEG-b-PCL micelles containing paclitaxel (PTX, cyclopamine (CYP, and gossypol (GSP at 30, 30, and 30 mg/kg, respectively, debulked tumor tissues by 1.3-fold, based on loss of bioluminescence with <10% body weight change, and induced apoptosis in peritoneal tumors when used as neoadjuvant chemotherapy (NACT in an ES-2-luc-bearing xenograft model for ovarian cancer. In a second step, a single intravenous (i.v. injection of apoptosis-targeting GFNFRLKAGAKIRFGS-PEG-b-PCL micelles containing a near-infrared (NIR fluorescence probe, DiR (1,1'-dioctadecyltetramethyl indotricarbocyanine iodide, resulted in increased peritoneal DiR accumulation in apoptosis-induced ES-2-luc tumor tissues (ex vivo by 1.5-fold compared with DiR molecules delivered by methoxy PEG-b-PCL micelles (non-targeted at 48 h after i.v. injection in a second step. As a result, a tandem of PEG-b-PCL micelles enabled high-resolution detection of ca. 1 mm diameter tumors, resulting in resection of approximately 90% of tumors, and a low peritoneal cancer index (PCI of ca. 7. Thus, a tandem of PEG-b-PCL micelles used for NCAT and NIR fluorescence imaging of therapy-induced apoptosis for intraoperative surgical guidance may be a promising treatment strategy for metastatic ovarian cancer.

  9. Direct Measurement of the Thermodynamics of Chiral Recognition in Bile Salt Micelles.

    Science.gov (United States)

    Anderson, Shauna L; Rovnyak, David; Strein, Timothy G

    2016-04-01

    Isothermal titration calorimetry (ITC) is shown to be a sensitive reporter of bile salt micellization and chiral recognition. Detailed ITC characterization of bile micelle formation as well as the chiral recognition capabilities of sodium cholate (NaC), deoxycholate (NaDC), and taurodeoxycholate (NaTDC) micelle systems are reported. The ΔH(demic) of these bile salt micelle systems is directly observable and is strongly temperature-dependent, allowing also for the determination of ΔCp(demic). Using the pseudo-phase separation model, ΔG(demic) and TΔS(demic) were also calculated. Chirally selective guest-host binding of model racemic compounds 1,1'-bi-2-napthol (BN) and 1,1'-binaphthyl-2,2'-diylhydrogenphosphate (BNDHP) to bile salt micelles was then investigated. The S-isomer was shown to bind more tightly to the bile salt micelles in all cases. A model was developed that allows for the quantitative determination of the enthalpic difference in binding affinity that corresponds to chiral selectivity, which is on the order of 1 kJ mol(-1).

  10. Oleyl-hyaluronan micelles loaded with upconverting nanoparticles for bio-imaging

    Energy Technology Data Exchange (ETDEWEB)

    Pospisilova, Martina, E-mail: martina.pospisilova@contipro.com; Mrazek, Jiri; Matuska, Vit; Kettou, Sofiane; Dusikova, Monika; Svozil, Vit; Nesporova, Kristina; Huerta-Angeles, Gloria; Vagnerova, Hana; Velebny, Vladimir [Contipro Biotech (Czech Republic)

    2015-09-15

    Hyaluronan (HA) represents an interesting polymer for nanoparticle coating due to its biocompatibility and enhanced cell interaction via CD44 receptor. Here, we describe incorporation of oleate-capped β–NaYF{sub 4}:Yb{sup 3+}, Er{sup 3+} nanoparticles (UCNP-OA) into amphiphilic HA by microemulsion method. Resulting structures have a spherical, micelle-like appearance with a hydrodynamic diameter of 180 nm. UCNP-OA-loaded HA micelles show a good stability in PBS buffer and cell culture media. The intensity of green emission of UCNP-OA-loaded HA micelles in water is about five times higher than that of ligand-free UCNP, indicating that amphiphilic HA effectively protects UCNP luminescence from quenching by water molecules. We found that UCNP-OA-loaded HA micelles in concentrations up to 50 μg mL{sup −1} increase cell viability of normal human dermal fibroblasts (NHDF), while viability of human breast adenocarcinoma cells MDA–MB–231 is reduced at these concentrations. The utility of UCNP-OA-loaded HA micelles as a bio-imaging probe was demonstrated in vitro by successful labelling of NHDF and MDA–MB–231 cells overexpressing the CD44 receptor.

  11. Micelles assembled with carbocyanine dyes for theranostic near-infrared fluorescent cancer imaging and photothermal therapy.

    Science.gov (United States)

    Yang, Hong; Mao, Huajian; Wan, Zhihui; Zhu, Aijun; Guo, Miao; Li, Yanli; Li, Xinming; Wan, Jiangling; Yang, Xiangliang; Shuai, Xintao; Chen, Huabing

    2013-12-01

    It is an emerging focus to explore a theranostic nanocarrier for simultaneous cancer imaging and therapy. Herein, we demonstrate a theranostic micelle system for cancer near infrared fluorescent (NIRF) imaging with enhanced signal to noise ratio and superior photothermal therapy. The copolymers consisting of monomethoxy poly(ethylene glycol) and alkylamine-grafted poly(L-aspartic acid) are assembled with carbocyanine dyes into theranostic micelles, which exhibit small size, high loading capacity, good stability, sustained release behavior, and enhanced cellular uptake. The micelles achieve the preferable biodistribution and long-term retention of carbocyanine dyes at tumor, which result in enhanced NIRF imaging by generating stable retention of NIRF signals at both hypervascular and hypovascular tumors during a long-term imaging period of up to 8 day, accompanying with negligible noise at normal tissues. The photostability of carbocyanine dye (Cypate) plays an important role for long-term cancer imaging with enhanced SNR. Moreover, the micelles exhibit severe photothermal damage on cancer cells via the destabilization of subcellular organelles upon photoirradiation, causing superior photothermal tumor regress. The micelles act as a powerful theranostic nanocarrier for simultaneous cancer imaging with high contrast and superior photothermal therapy.

  12. Shape Transformation of Light-Responsive Pyrene-Containing Micelles and Their Influence on Cytoviability.

    Science.gov (United States)

    Wang, Haisheng; Zhang, Wenbo; Gao, Changyou

    2015-08-10

    The amphiphilic pyrene-containing random copolymers with light-responsive pyrene ester bonds were synthesized by copolymerizing 1-pyrenemethyl acrylate (PA) and N,N-dimethylacrylamide (DMA). The P(DMA-co-PA) copolymers formed spherical micelles in water, which were transformed into nanorods as a result of cleavage of the pyrene ester bonds under UV irradiation. In vitro culture with A549 cells and Raw cells showed that compared to the nonphotodegradable ones, the photodegradable P(DMA-co-PA) micelles caused significantly higher cytotoxicity under the same UV irradiation. The intracellular reactive oxygen species (ROS) level had a positive correlation with the cytotoxicity regardless of the cell types. The nonphotodegradable pyrene-containing micelles produced a lower level of ROS under UV irradiation. However, the photodecomposable P(DMA-co-PA) micelles produced a significant higher level of ROS under the same trigger of UV irradiation, which caused the shape transformation of micelles to nanorods and higher cytotoxicity simultaneously. PMID:26133965

  13. Mesoscopic simulation studies on the formation mechanism of drug loaded polymeric micelles.

    Science.gov (United States)

    Wang, Yan; Zhu, Dan Dan; Zhou, Jian; Wang, Qi Lei; Zhang, Can Yang; Liu, Yue Jin; Wu, Zhi Min; Guo, Xin Dong

    2015-12-01

    In this work, the formation of polymeric micelles as drug delivery vehicles in an aqueous environment is investigated by dissipative particle dynamics (DPD) simulations. Doxorubicin (DOX) is selected as the model drug, whereas docosahexaenoic acid (DHA) conjugated His10Lys10 (DHA-His10Lys10) as the drug carrier. It is shown from DPD simulation that drug molecules and DHA-His10Lys10 molecules could aggregate and form micelles under a defined composition recipe; drug molecules are homogeneously distributed inside the carrier matrix, on whose surface the stabilizer lysine segments are absorbed. Under different compositions of drug and water, aggregate morphologies of polymeric micelles are observed as spherical, columnar, and lamellar structures. We finally proposed the formation mechanism of drug loaded polymeric micelles and apply it in practice by analyzing the simulated phenomena. All the results can effectively guide the experimental preparation of drug delivery system with desired properties or explore a novel polymeric micelle with high performance. PMID:26454543

  14. Solubilization of n-alkylbenzenes into gemini surfactant micelles in aqueous medium.

    Science.gov (United States)

    Nakahara, Hiromichi; Kojima, Yui; Moroi, Yoshikiyo; Shibata, Osamu

    2014-05-27

    Solubilization of benzene, toluene, ethylbenzene, n-propylbenzene, n-butylbenzene, and n-pentylbenzene into micelles of decanediyl-1-10-bis(dimethyltetradecylammonium bromide) (14-10-14,2Br(-)) has been investigated in the temperature range from 288.2 to 308.2 K. The equilibrium concentrations of all the solubilizates are determined spectrophotometrically. The concentration of the solubilizates remains constant below the critical micelle concentration (cmc) and increases linearly with an increase in 14-10-14,2Br(-) concentration above the cmc. Compared to the mother micelle, the solubilized micelles indicate much larger hydrodynamic diameters, which are determined by dynamic light scattering. Therefore, the Gibbs energy change for the solubilization of n-alkylbenzenes has been evaluated by the partitioning of the solubilizates between the aqueous and micellar phases. Furthermore, the enthalpy and entropy changes for the solubilization could be calculated from temperature dependence of the Gibbs energy change. From the thermodynamic parameters, it is found that the solubilization for the present system is entropy-driven and that the location of the solubilizates moves into the inner core of the micelle with an elongation of their alkyl chains. The movement on the location is also supported by the results of absorption spectra, Fourier transform infrared (FTIR) spectra, and two-dimensional nuclear Overhauser effect spectroscopy (2-D NOESY). PMID:24802668

  15. Comparative evaluation of polymersome versus micelle structures as vehicles for the controlled release of drugs

    Energy Technology Data Exchange (ETDEWEB)

    Alibolandi, Mona [Mashhad University of Medical Sciences, Biotechnology Research Center, School of Pharmacy (Iran, Islamic Republic of); Ramezani, Mohammad; Abnous, Khalil [Mashhad University of Medical Sciences, Pharmaceutical Research Center, School of Pharmacy (Iran, Islamic Republic of); Sadeghi, Fatemeh, E-mail: sadeghif@mums.ac.ir [Mashhad University of Medical Sciences, Targeted Drug Delivery Research Center, School of Pharmacy (Iran, Islamic Republic of); Hadizadeh, Farzin, E-mail: hadizadehf@mums.ac.ir [Mashhad University of Medical Sciences, Biotechnology Research Center, School of Pharmacy (Iran, Islamic Republic of)

    2015-02-15

    Di-block copolymers composed of two biocompatible polymers, poly(ethylene glycol) and poly(d,l-lactide), were synthesized by ring-opening polymerization for the preparation of doxorubicin-loaded self-assembled nanostructures, including polymeric vesicles (polymersomes) and micelles. The capability and stability of the nanostructures prepared for the controlled release of DOX are discussed in this paper. The in vitro drug release at 37 °C was evaluated up to 6 days at pH 7.4 and 5.5 and in the presence of 50 % FBS. The cellular uptake and cytotoxicity effect of both formulations were also evaluated in the MCF-7 cell line. The SEM and AFM images confirmed the hollow spherical structure of the polymersomes and the solid round structures of the micelles. The TEM results also revealed the uniformity in size and shape of the drug-loaded micelle and polymersome nanostructures. The DOX-loaded micelles and polymersomes presented efficient anticancer performance, as verified by flow cytometry and MTT assay tests. The most important finding of this study is that the prepared nanopolymersomes presented significant increases in the doxorubicin encapsulation efficiency and the stability of the formulation in comparison with the micelle formulation. In vitro studies revealed that polymersomes may be stable in the blood circulation and meet the requirements for an effective drug delivery system.

  16. Photoinduced electron transfer and geminate recombination in the group head region of micelles

    International Nuclear Information System (INIS)

    A pump-probe spectroscopic study of photoinduced forward electron transfer and geminate recombination between donors and acceptors located in the head group regions of micelles is presented. The hole donor is octadecyl-rhodamine B (ODRB) and the hole acceptor is N,N-dimethyl-aniline (DMA). The experiments are conducted as a function of the DMA concentration in the dodecyltrimethylammonium bromide and tetradecyltrimethylammonium bromide micelles. In spite of the fact that the absorptions of both the ODRB radical and ground state bleach spectrally overlap with the ODRB excited state absorption, a procedure that makes it possible to determine the geminate recombination dynamics is presented. These experiments are the first to measure the dynamics of geminate recombination in micelles, and the experiments have two orders of magnitude better time resolution than previous studies of forward transfer. The experimental data are compared to statistical mechanics theoretical calculations of both the forward transfer and the geminate recombination. The theory includes important aspects of the topology of the micelle and the diffusion of the donor-acceptors in the micelle head group region. A semiquantitative but nonquantitative agreement between theory and experiments is achieved

  17. Small angle neutron scattering study of doxorubicin–surfactant complexes encapsulated in block copolymer micelles

    Indian Academy of Sciences (India)

    Jayita Bhattacharjee; Gunjan Verma; V K Aswal; P A Hassan

    2008-11-01

    Self-assembling behaviour of block copolymers and their ability to evade the immune system through polyethylene oxide stealth makes it an attractive candidate for drug encapsulation. Micelles formed by polyethylene oxide–polypropylene oxide–polyethylene oxide triblock copolymers (PEO–PPO–PEO), pluronic P123, have been employed for encapsulating the anti-cancer drug doxorubicin hydrochloride. The binding affinity of doxorubicin within the micelle carrier is enhanced through complex formation of drug and anionic surfactant, aerosol OT (AOT). Electrostatic binding of doxorubicin with negatively charged surfactants leads to the formation of hydrophobic drug–surfactant complexes. Surfactant-induced partitioning of the anti-cancer drug into nonpolar solvents such as chloroform is investigated. SANS measurements were performed on pluronic P123 mi-celles in the presence of drug–surfactant complex. No significant changes in the structure of the micelles are observed upon drug encapsulation. This demonstrates that surfactant–drug complexes can be encapsulated in block copolymer micelles without disrupting the structure of aggregates.

  18. Cellular internalization and in vivo tracking of thermosensitive luminescent micelles based on luminescent lanthanide chelate.

    Science.gov (United States)

    Li, Yong-Yong; Cheng, Han; Zhang, Zhi-Guo; Wang, Chang; Zhu, Jing-Ling; Liang, Yong; Zhang, Ke-Li; Cheng, Si-Xue; Zhang, Xian-Zheng; Zhuo, Ren-Xi

    2008-01-01

    An amphiphilic tris(dibenzoylmethanato)europium(III) (Eu(DBM)(3)) coordinated P(MMA-co-EIPPMMA)-co-P(NIPAAm-co-NDAPM) copolymer was synthesized, which exhibited good biocompatibility and emitted strong red luminescence (MMA, methyl methacrylate; EIPPMMA, 4-(1-ethyl-1H-imidazo[4,5-f][1,10]phenanthrolin-2-yl)phenyl methacrylate; NIPAAm, N-isopropylacrylamide; NDAPM, (N-(3-dimethylamino)propyl)methacrylamide). The copolymer could self-assemble into micelles of size around 260 nm, and the micelles were thermosensitive at around body temperature. The drug-loaded micelles showed thermosensitive controlled drug release, and the paclitaxel loaded micelles were capable of being internalized into the tumor cells (A549) and exhibited obvious inhibition to the growth of A549 cells. Importantly, in vivo study showed the self-assembled micelles of Eu(DBM)(3) coordinated P(MMA-co-EIPPMMA)-co-P(NIPAAm-co-NDAPM) copolymer uptaken by the larvae of zebrafish could be easily tracked and be eliminated from the body within several days. PMID:19206556

  19. Entropic effects, shape, and size of mixed micelles formed by copolymers with complex architectures.

    Science.gov (United States)

    Kalogirou, Andreas; Gergidis, Leonidas N; Moultos, Othonas; Vlahos, Costas

    2015-11-01

    The entropic effects in the comicellization behavior of amphiphilic AB copolymers differing in the chain size of solvophilic A parts were studied by means of molecular dynamics simulations. In particular, mixtures of miktoarm star copolymers differing in the molecular weight of solvophilic arms were investigated. We found that the critical micelle concentration values show a positive deviation from the analytical predictions of the molecular theory of comicellization for chemically identical copolymers. This can be attributed to the effective interactions between copolymers originated from the arm size asymmetry. The effective interactions induce a very small decrease in the aggregation number of preferential micelles triggering the nonrandom mixing between the solvophilic moieties in the corona. Additionally, in order to specify how the chain architecture affects the size distribution and the shape of mixed micelles we studied star-shaped, H-shaped, and homo-linked-rings-linear mixtures. In the first case the individual constituents form micelles with preferential and wide aggregation numbers and in the latter case the individual constituents form wormlike and spherical micelles. PMID:26651715

  20. Alteration of membrane phospholipid methylation by adenosine analogs does not affect T lymphocyte activation

    International Nuclear Information System (INIS)

    Membrane phospholipid methylation has been described during activation of various immune cells. Moreover recent data indicated modulation of immune cells functions by adenosine. As S-adenosyl-methionine and S-adenosyl-homocysteine are adenosine analogs and modulators of transmethylation reactions, the effects of SAH and SAM were investigated on membrane phospholipid methylation and lymphocyte activation. SAM was shown to induce the membrane phospholipid methylation as assessed by the 3Hmethyl-incorporation in membrane extract. This effect was inhibited by SAH. In contrast SAM and SAH did not affect the phytohemagglutinin-induced proliferative response of peripheral blood mononuclear cells. SAH neither modified the early internalization of membrane CD3 antigens nor did it prevent the late expression of HLA-DR antigens on lymphocytes activated by phytohemagglutinin. These results indicate that in vitro alteration of phospholipid methylation does not affect subsequent steps of human T lymphocyte activation and proliferation

  1. Transporting of a Cell-Sized Phospholipid Vesicle Across Water/Oil Interface

    CERN Document Server

    Hase, M; Hamada, T; Yoshikawa, K; Hase, Masahiko; Yamada, Ayako; Hamada, Tsutomu; Yoshikawa, Kenichi

    2006-01-01

    When a cell-sized water droplet, with a diameter of several tens of micro meter, is placed in oil containing phospholipids, a stable cell-sized vesicle is spontaneously formed as a water-in-oil phospholipid emulsion (W/O CE) with a phospholipid monolayer. We transferred the lipid vesicle thus formed in the oil phase to the water phase across the water/oil interface by micromanipulation, which suggests that the vesicle is transformed from a phospholipid monolayer as W/O CE into a bilayer. The lipid vesicle can then be transported back into the oil phase. This novel experimental procedure may be a useful tool for creating a model cellular system, which, together with a microreactor, is applicable as a micrometer-scale biochemical reaction field.

  2. Transbilayer dynamics of phospholipids in the plasma membrane of the Leishmania genus.

    Directory of Open Access Journals (Sweden)

    Marcos Gonzaga dos Santos

    Full Text Available Protozoans of the Leishmania genus are the etiological agents of a wide spectrum of diseases commonly known as leishmaniases. Lipid organization of the plasma membrane of the parasite may mimic the lipid organization of mammalian apoptotic cells and play a role in phagocytosis and parasite survival in the mammal host. Here, we analyzed the phospholipid dynamics in the plasma membrane of both the L. (Leishmania and the L. (Viannia subgenera. We found that the activity and substrate specificity of the inward translocation machinery varied between Leishmania species. The differences in activity of inward phospholipid transport correlated with the different sensitivities of the various species towards the alkyl-phospholipid analogue miltefosine. Furthermore, all species exhibited a phospholipid scramblase activity in their plasma membranes upon stimulation with calcium ionophores. However, binding of annexin V to the parasite surface was only detected for a subpopulation of parasites during the stationary growth phase and only marginally enhanced by scramblase activation.

  3. Effect of oral treatment with pantethine on platelet and plasma phospholipids in IIa hyperlipoproteinemia.

    Science.gov (United States)

    Prisco, D; Rogasi, P G; Matucci, M; Paniccia, R; Abbate, R; Gensini, G F; Neri Serneri, G G

    1987-03-01

    In a single-blind, crossover, completely randomized study, the effects of oral treatment with pantethine or placebo on fatty acid composition of plasma and platelet phospholipids were investigated in 10 IIa hyperlipoproteinemic patients. A significant decrease of total cholesterol and total phospholipids was observed both in plasma and in platelets after a twenty-eight-day treatment. In plasma, pantethine induced a decrease of the ratio sphingomyelin/phosphatidylcholine. Moreover, a relative increase of n3-polyunsaturated fatty acids both in plasma and in platelet phospholipids and a decrease of arachidonic acid in plasma phospholipids were observed. These results indicate that pantethine can affect plasma and platelet lipid composition with possibly favorable influences on the determinants of cell membrane fluidity. PMID:3551695

  4. Complex coacervate core micelles with a lysozyme-modified corona.

    Science.gov (United States)

    Danial, Maarten; Klok, Harm-Anton; Norde, Willem; Stuart, Martien A Cohen

    2007-07-17

    This paper describes the preparation, characterization, and enzymatic activity of complex coacervate core micelles (C3Ms) composed of poly(acrylic acid) (PAA) and poly(N-methyl-2-vinyl pyridinium iodide)-b-poly(ethylene oxide) (PQ2VP-PEO) to which the antibacterial enzyme lysozyme is end-attached. C3Ms were prepared by polyelectrolyte complex formation between PAA and mixtures containing different ratios of aldehyde and hydroxyl end-functionalized PQ2VP-PEO. This resulted in the formation of C3Ms containing 0-40% (w/w) of the aldehyde end-functionalized PQ2VP-PEO block copolymer (PQ2VP-PEO-CHO). Chemical conjugation of lysozyme was achieved via reductive amination of the aldehyde groups, which are exposed at the surface of the C3M, with the amine groups present in the side chains of the lysine residues of the protein. Dynamic and static light scattering indicated that the conjugation of lysozyme to C3Ms prepared using 10 and 20% (w/w) PQ2VP-PEO-CHO resulted in the formation of unimicellar particles. Multimicellar aggregates, in contrast, were obtained when lysozyme was conjugated to C3Ms prepared using 30 or 40% (w/w) PQ2VP-PEO-CHO. The enzymatic activity of the unimicellar lysozyme-C3M conjugates toward the hydrolysis of the bacterial substrate Micrococcus lysodeikticus was comparable to that of free lysozyme. For the multimicellar particles, in contrast, significantly reduced enzymatic rates of hydrolysis, altered circular dichroism, and red-shifted tryptophan fluorescence spectra were measured. These results are attributed to the occlusion of lysozyme in the interior of the multimicellar conjugates.

  5. Analysis of phospholipids in microalga Nitzschia closterium by UPLC-Q-TOF-MS

    Institute of Scientific and Technical Information of China (English)

    严小军; 李海英; 徐继林; 周成旭

    2010-01-01

    Precise structural identification of phospholipids in the microalga Nitzschia closterium has been established using ultra performance liquid chromatography-electrospray ionization-quadrupole-time of flight-mass spectrometry (UPLC-ESI-Q-TOF-MS) for direct analysis of total lipid extracts.Mass spectrometry was performed in reflective time-of-flight using electron spraying ionization in negative mode.Phospholipid molecular species identification was based on the characteristic product ions and neutral loss yie...

  6. Phospholipid liposomes acquire apolipoprotein E in atherogenic plasma and block cholesterol loading of cultured macrophages.

    OpenAIRE

    Williams, K J; Tall, A.R.; Bisgaier, C; Brocia, R

    1987-01-01

    A single infusion of phospholipid liposomes promptly and persistently abolished the ability of hypercholesterolemic rabbit plasma to cause cholesteryl ester loading in cultured macrophages. This phospholipid enrichment of plasma caused moderate stimulation of cellular cholesterol efflux and, unexpectedly, almost complete inhibition of cellular uptake of beta-very low density lipoprotein (beta-VLDL), the major cholesteryl ester-rich particle in hypercholesterolemic rabbit plasma. Cell viabilit...

  7. Reduction of peritoneal carcinomatosis by intraperitoneal administration of phospholipids in rats

    OpenAIRE

    Otto Jens; Jansen Petra; Lucas Stefan; Schumpelick Volker; Jansen Marc

    2007-01-01

    Abstract Background Intraperitoneal tumor cell attachment after resection of gastrointestinal cancer may lead to a developing of peritoneal carcinosis. Intraabdominal application of phospholipids shows a significant decrease of adhesion formation even in case of rising tumor cell concentration. Methods In experiment A 2*106 colonic tumor cells (DHD/K12/Trb) were injected intraperitonely in female BD-IX-rats. A total of 30 rats were divided into three groups with treatments of phospholipids at...

  8. Regulation of phospholipid synthesis in phosphatidylserine synthase-deficient (chol) mutants of Saccharomyces cerevisiae.

    OpenAIRE

    Letts, V A; Henry, S. A.

    1985-01-01

    chol mutants of Saccharomyces cerevisiae are deficient in the synthesis of the phospholipid phosphatidylserine owing to lowered activity of the membrane-associated enzyme phosphatidylserine synthase. chol mutants are auxotrophic for ethanolamine or choline and, in the absence of these supplements, cannot synthesize phosphatidylethanolamine or phosphatidylcholine (PC). We exploited these characteristics of the chol mutants to examine the regulation of phospholipid metabolism in S. cerevisiae. ...

  9. Effect of gentamicin on phospholipid metabolism in cultured rabbit proximal tubular cells

    International Nuclear Information System (INIS)

    We examined the hypothesis that the accumulation of phospholipid in cells exposed to gentamicin is due to impaired degradation. Experiments were performed in rabbit proximal tubular cells grown in primary culture. Cells exposed to 10(-3) M gentamicin manifested myeloid body formation and a progressive increase in total phospholipid that by day 6 was 44% higher than that of control cells and reflected increases of phosphatidylinositol of 235%, phosphatidylcholine of 60%, phosphatidylethanolamine of 90%, and phosphatidylserine of 55% above control values. Gentamicin impaired the degradation of these phospholipids. The t1/2 of the phospholipid pool labeled with [3H]myoinositol increased 146% from 1.17 (control) to 2.88 days (gentamicin); the t1/2 of the [3H]choline pool increased 34% from 1.77 to 2.38 days; the t1/2 of the [3H]ethanolamine pool increased 57% from 3.14 to 4.93 days; the t1/2 of the [3H] serine pool increased 37% from 6.30 to 8.63 days. Exposure of cells to gentamicin for 2 days also stimulated increased incorporation of [3H]myoinositol (68%) and [3H]ethanolamine (59%) into phospholipid. The data are consistent with the hypothesis that gentamicin inhibits the activity of lysosomal phospholipases that results in the accumulation of phospholipid within the lysosome in the form of myeloid bodies. Increased phospholipid synthesis may represent a compensatory response to the impaired lysosomal degradation of phospholipid. We postulate that the preferential increase of phosphatidylinositol reflects the capacity of the polycationic gentamicin to interact electrostatically with the anionic phosphoinositides and inhibit their turnover

  10. Serum Phospholipid Fatty Acids and Prostate Cancer Risk: Results From the Prostate Cancer Prevention Trial

    OpenAIRE

    Brasky, Theodore M.; Till, Cathee; White, Emily; Neuhouser, Marian L; Song, Xiaoling; Goodman, Phyllis; Thompson, Ian M; King, Irena B.; Albanes, Demetrius; Kristal, Alan R.

    2011-01-01

    Inflammation may be involved in prostate cancer development and progression. This study examined the associations between inflammation-related phospholipid fatty acids and the 7-year-period prevalence of prostate cancer in a nested case-control analysis of participants, aged 55–84 years, in the Prostate Cancer Prevention Trial during 1994–2003. Cases (n = 1,658) were frequency matched to controls (n = 1,803) on age, treatment, and prostate cancer family history. Phospholipid fatty acids were ...

  11. Effect of gramicidin A on the dipole potential of phospholipid membranes.

    OpenAIRE

    Shapovalov, V L; Kotova, E A; Rokitskaya, T I; Antonenko, Y N

    1999-01-01

    The effect of channel-forming peptide gramicidin A on the dipole potential of phospholipid monolayers and bilayers has been studied. Surface pressure and surface potential isotherms of monolayers have been measured with a Langmuir trough equipped with a Wilhelmy balance and a surface potential meter (Kelvin probe). Gramicidin has been shown to shift pressure-area isotherms of phospholipids and to reduce their monolayer surface potentials. Both effects increase with the increase in gramicidin ...

  12. VISUALIZATION AND ANALYSIS OF LPS DISTRIBUTION IN BINARY PHOSPHOLIPID BILAYERS

    Science.gov (United States)

    Florencia, Henning María; Susana, Sanchez; Laura, Bakás

    2010-01-01

    Lipopolysaccharide (LPS) is an endotoxin released from the outer membrane of Gram negative bacteria during infections. It have been reported that LPS may play a rol in the outer membrane of bacteria similar to that of cholesterol in eukaryotic plasma membranes. In this article we compare the effect of introducing LPS or cholesterol in liposomes made of dipalmitoylphosphatidylcholine/dioleoylphosphatidylcholine on the solubilization process by Triton X-100. The results show that liposomes containing LPS or Cholesterol are more resistant to solubilization by Triton X-100 than the binary phospholipid mixtures at 4°C. The LPS distribution was analyzed on GUVs of DPPC:DOPC using FITC-LPS. Solid and liquid-crystalline domains were visualized labeling the GUVs with LAURDAN and GP images were acquired using a two-photon microscope. The images show a selective distribution of LPS in gel domains. Our results support the hypothesis that LPS could aggregate and concentrate selectively in biological membranes providing a mechanism to bring together several components of the LPS-sensing machinery. PMID:19324006

  13. Probing Lipid Membrane Rafts (Microdomains) with Fluorescent Phospholipids

    Science.gov (United States)

    Gu, Yongwen; Mitchel, Drake

    2011-10-01

    Membrane rafts are enriched in sphingolipids and cholesterol, they exist in a more ordered state (the liquid-ordered phase; lo) than the bulk membrane (the liquid-disordered phase; ld). Ternary mixtures of palmitoyl-oleoyl-phosphocholine (POPC; 16:0,18:1 PC), sphingomyelin (SPM), and cholesterol (Chol) form membrane rafts over a wide range of molar ratios. We are examining the ability of two fluorescent probes, NBD linked to di-16:0 PE which partitions into the lo phase, and NBD linked to di-18:1 PE which partitions into the ld phase, to detect these two phases. We are also examining the effect of the highly polyunsaturated phospholipid stearoyl-docosahexanoyl-phosphocholine (SDPC; 18:0, 22:6 PC) on the size and stability of POPC/SPM/Chol membrane rafts. We report on the fluorescence lifetime and anisotropy decay dynamics of two fluorescent probes. Data were acquired via frequency-domain measurements from 5 to 250 MHz.

  14. Synthesis and characterisation of cationically modified phospholipid polymers.

    Science.gov (United States)

    Lewis, Andrew L; Berwick, James; Davies, Martyn C; Roberts, Clive J; Wang, Jin-Hai; Small, Sharon; Dunn, Anthony; O'Byrne, Vincent; Redman, Richard P; Jones, Stephen A

    2004-07-01

    Phospholipid-like copolymers based on 2-(methacryloyloxyethyl) phosphorylcholine were synthesised using monomer-starved free radical polymerisation methods and incorporating cationic charge in the form of the choline methacrylate monomer in amounts varying from 0 to 30 wt%, together with a 5 wt% silyl cross-linking agent in order to render them water-insoluble once thermally cured. Characterisation using a variety of techniques including nuclear magnetic resonance spectroscopy, high-pressure liquid chromatography and gel permeation chromatography showed the cationic monomer did not interfere with the polymerisation and that the desired amount of charge had been incorporated. Gravimetric and differential scanning calorimetry methods were used to evaluate the water contents of polymer membranes cured at 70 degrees C, which was seen to increase with increasing cation content, producing materials with water contents ranging from 50% to 98%. Surface plasmon resonance indicated that the coatings swelled rapidly in water, the rate and extent of swelling increasing with increasing cation level. Dynamic contact angle showed that coatings of all the polymers possessed a hydrophobic surface when dry in air, characteristic of the alkyl chains expressed at the surface (>100 degrees advancing angle). Rearrangement of the hydrophilic groups to the surface occurred once wet, to produce highly wettable surfaces with a decrease in advancing angle with increasing cation content. Atomic force microscopy showed all polymer films to be smooth with no features in topographical or phase imaging. Mechanical properties of the dry films were also unaffected by the increase in cation content.

  15. Essential phospholipids in fatty liver: a scientific update

    Science.gov (United States)

    Gundermann, Karl-Josef; Gundermann, Simon; Drozdzik, Marek; Mohan Prasad, VG

    2016-01-01

    Aim Although essential phospholipids (EPL) from soybean are often used in membrane-associated disorders and diseases, their high quality of purification and effects on prevalent liver diseases, especially on fatty liver diseases (FLDs) of different origin, are still widely unknown and a matter of continuous active research. The aim of this article is to review, discuss, and summarize the available results of EPL in the treatment of FLD. Methods Database research was carried out on Medline, Embase, Cochrane Library, country-specific journals, and follow-up literature citations for relevant hepatogastroenterological articles published between 1988 and 2014. We searched for and reviewed only those papers that indicated minimum extraction amount of 72% (3-sn-phosphatidyl)choline from soybean as being necessary to treat patients with a considerable amount of 1,2-dilinoleoylphosphatidylcholine as a key component in EPL. Results EPL has a well-established mode of action, therapeutic effectiveness, and lack of toxicity, which ensures clinically relevant efficacy-to-safety ratio. It influences membrane- dependent cellular functions and shows anti-inflammatory, antioxidant, antifibrogenic, anti apoptotic, membrane-protective, and lipid-regulating effects. Due to its positive effects on membrane composition and functions, it accelerates the improvement or normalization of subjective symptoms; pathological, clinical, and biochemical findings; hepatic imaging; and liver histology. It is justified to administer EPL together with other therapeutic measurements in the liver. Conclusion Pharmacological and clinical results confirm the efficacy of EPL in the treatment of FLD. PMID:27217791

  16. Anisotropic metal growth on phospholipid nanodiscs via lipid bilayer expansion.

    Science.gov (United States)

    Oertel, Jana; Keller, Adrian; Prinz, Julia; Schreiber, Benjamin; Hübner, René; Kerbusch, Jochen; Bald, Ilko; Fahmy, Karim

    2016-01-01

    Self-assembling biomolecules provide attractive templates for the preparation of metallic nanostructures. However, the intuitive transfer of the "outer shape" of the assembled macromolecules to the final metallic particle depends on the intermolecular forces among the biomolecules which compete with interactions between template molecules and the metal during metallization. The shape of the bio-template may thus be more dynamic than generally assumed. Here, we have studied the metallization of phospholipid nanodiscs which are discoidal particles of ~10 nm diameter containing a lipid bilayer ~5 nm thick. Using negatively charged lipids, electrostatic adsorption of amine-coated Au nanoparticles was achieved and followed by electroless gold deposition. Whereas Au nanoparticle adsorption preserves the shape of the bio-template, metallization proceeds via invasion of Au into the hydrophobic core of the nanodisc. Thereby, the lipidic phase induces a lateral growth that increases the diameter but not the original thickness of the template. Infrared spectroscopy reveals lipid expansion and suggests the existence of internal gaps in the metallized nanodiscs, which is confirmed by surface-enhanced Raman scattering from the encapsulated lipids. Interference of metallic growth with non-covalent interactions can thus become itself a shape-determining factor in the metallization of particularly soft and structurally anisotropic biomaterials. PMID:27216789

  17. Determination of phospholipid transfer proteins in rat tissues by immunoassays

    International Nuclear Information System (INIS)

    Several quantitative immunoassays have been developed for two phospholipid transfer proteins from rat liver, i.e. the phosphatidylcholine transfer protein and the non-specific lipid transfer protein. The development of a double-antibody radioimmunoassay for the phosphatidylcholine transfer protein is described. The transfer protein was labelled with iodine-125 by the mild glucose oxidase-lactoperoxidase method. Although less than one tyrosine residue per molecule of transfer protein was labelled, only 20% of the labelled transfer protein was immunoprecipitable. This value could be increased to 80% by purifying the labelled protein by affinity chromatography on a column of anti-phosphatidylcholine transfer protein-IgG coupled to Sepharose 4B. The radioimmunoassay was used to determine the levels of phosphatidylcholine transfer protein in homogenates and 105 000 xg supernatants from various rat tissues as well as several Morris hepatomas. An enzyme immunoassay for the non-specific lipid transfer protein is also described. The antiserum that was raised especially by the author was cross-reactive with the non-specific lipid transfer protein present in 105 000 xg supernatants from human, mouse and bovine liver. The non-specific lipid transfer protein lost its immunoreactivity upon labelling with iodine-125 using different labelling techniques. Therefore, a regular radioimmunoassay could not be developed. The results of these different assays were compared. (Auth.)

  18. Oral absorption of hyaluronic acid and phospholipids complexes in rats

    Institute of Scientific and Technical Information of China (English)

    Si-Ling Huang; Pei-Xue Ling; Tian-Min Zhang

    2007-01-01

    AIM: To prepare a complex of hyaluronic acid (HA) and phospholipids (PL), and study the improvement effect of PL on the oral absorption of HA.METHODS: The complex of HA-PL (named Haplex) was prepared by film dispersion and sonication method, its physico-chemical properties were identified by infrared spectra and differential scanning calorimetry (DSC). The oral absorption of Haplex was studied. Thirty-two healthy rats were divided into 4 groups randomly: (1) a normal saline (NS) control group; (2) an HA group; (3) a mixture group and (4) a Haplex group. After intragastric administration, the concentration of HA in serum was determined.RESULTS: The physico-chemical properties of Haplex were different from HA or PL or their mixture. After Haplex was administered to rats orally, the serum concentration of HA was increased when compared with the mixture or HA control groups from 4 h to 10 h (P < 0.05). The ΔAUCo-12 h of Haplex was also greater than that of the other three groups (P < 0.05).CONCLUSION: The method of film dispersion and sonication can prepare HA and PL complex, and PL can enhance the oral absorption of exogenous HA.

  19. Isolation and Analysis of Phospholipids in Dairy Foods.

    Science.gov (United States)

    Pimentel, Lígia; Gomes, Ana; Pintado, Manuela; Rodríguez-Alcalá, Luis Miguel

    2016-01-01

    The lipid fraction of milk is one of the most complex matrixes in foodstuffs due to the presence of a high number of moieties with different physical and chemical properties. Glycerolipids include glycerol and two fatty acids esterified in positions sn-1 and sn-2 with higher concentration of unsaturated fatty acids than in the triglyceride fraction of milk. Sphingolipids consist of a sphingoid base linked to a fatty acid across an amide bond. Their amphiphilic nature makes them suitable to be added into a variety of foods and recent investigations show that phospholipids, mainly phosphatidylserine and sphingomyelin, can exert antimicrobial, antiviral, and anticancer activities as well as positive effects in Alzheimer's disease, stress, and memory decline. Polar lipids can be found as natural constituents in the membranes of all living organisms with soybean and eggs as the principal industrial sources, yet they have low contents in phosphatidylserine and sphingomyelin. Animal products are rich sources of these compounds but since there are legal restrictions to avoid transmission of prions, milk and dairy products are gaining interest as alternative sources. This review summarizes the analysis of polar lipids in dairy products including sample preparation (extraction and fractionation/isolation) and analysis by GC or HPLC and the latest research works using ELSD, CAD, and MS detectors. PMID:27610267

  20. Primary Structural Characterization of Phospholipid Hydroperoxide Glutathione Peroxidase

    Institute of Scientific and Technical Information of China (English)

    王泽斌; 杨晓东; 赵南明; 刘进元

    2002-01-01

    More than 20 sequences of phospholipid hydroperoxide glutathione peroxidase (PHGPX) from a sequence database were analyzed. The analyses show that the primary structures of most PHGPX proteins have three highly conserved regions forming a catalytic center and have more than 50% amino acid sequence identity in common. However, two PHGPXs from bovine and swine with the same function have very low similarity with typical PHGPXs and do not have the three highly conserved regions. Thus, the PHGPX proteins are divided into two types: those with the three highly conserved regions, designated as PHGPX-I, and the others as PHGPX-II. In general, type I proteins are composed of ca.170 amino acid residues; a few of them have an extra signal peptide sequence at the N-terminal of the protein. The composition of plant and animal PHGPX amino acids is very different, with most plant PHGPXs being weak acidic, while most animal ones are alkaline. Another specific conservative motif is also found in plant PHGPX proteins. System evolution analysis shows that ortholog and paralog evolution models both exist in PHGPXs, with the plant PHGPX and the animal PHGPX diverging exclusively into two branches in PHGPX-I. The information revealed by the evolution tree agrees with the general species evolution process from low to advanced and from simple to complicated.

  1. Incorporation of peptides in phospholipid aggregates using ultrasound.

    Science.gov (United States)

    Silva, Raquel; Little, Collin; Ferreira, Helena; Cavaco-Paulo, Artur

    2008-09-01

    This study presents the highlights of ultrasonic effects on peptides incorporated on phospholipid aggregates (liposomes). These liposomes or vesicles are known as transport agents in skin drug delivery and for hair treatment. They might be a good model to deliver larger peptides into hair to restore fibre strength after hair coloration, modelling, permanent wave and/or straightening. The preparation of liposomes 1,2-dipalmitoyl-sn-glycerol-3-phosphocholine (DPPC) with peptides (LLLLK LLLLK LLLLK LLLLK; LLLLL LCLCL LLKAK AK) was made by the thin film hydration method. The LUVs (uni-lamellar vesicles) were obtained by sonication, applying different experimental conditions, such as depth (mm) and power intensity (%). Photon-correlation spectroscopy (PCS) and electronic microscopy (EM) results confirmed that the incorporation of these peptides, with different sequence of amino acids, presented differences on the diameter, zeta-potential of membrane surface and shape of liposomes. The liposomes that included peptide LLLLK LLLLK LLLLK LLLLK present an increased in zeta-potential values after using ultrasound and an "amorphous" aspect. Conversely, the liposomes that incorporated the peptide LLLLL LCLCL LLKAK AK presented a define shape (rod shape) and the potential surface of liposome did not change significantly by the use of ultrasound. PMID:18467154

  2. Isolation and Analysis of Phospholipids in Dairy Foods

    Directory of Open Access Journals (Sweden)

    Lígia Pimentel

    2016-01-01

    Full Text Available The lipid fraction of milk is one of the most complex matrixes in foodstuffs due to the presence of a high number of moieties with different physical and chemical properties. Glycerolipids include glycerol and two fatty acids esterified in positions sn-1 and sn-2 with higher concentration of unsaturated fatty acids than in the triglyceride fraction of milk. Sphingolipids consist of a sphingoid base linked to a fatty acid across an amide bond. Their amphiphilic nature makes them suitable to be added into a variety of foods and recent investigations show that phospholipids, mainly phosphatidylserine and sphingomyelin, can exert antimicrobial, antiviral, and anticancer activities as well as positive effects in Alzheimer’s disease, stress, and memory decline. Polar lipids can be found as natural constituents in the membranes of all living organisms with soybean and eggs as the principal industrial sources, yet they have low contents in phosphatidylserine and sphingomyelin. Animal products are rich sources of these compounds but since there are legal restrictions to avoid transmission of prions, milk and dairy products are gaining interest as alternative sources. This review summarizes the analysis of polar lipids in dairy products including sample preparation (extraction and fractionation/isolation and analysis by GC or HPLC and the latest research works using ELSD, CAD, and MS detectors.

  3. Isolation and Analysis of Phospholipids in Dairy Foods

    Science.gov (United States)

    Pimentel, Lígia; Gomes, Ana; Pintado, Manuela

    2016-01-01

    The lipid fraction of milk is one of the most complex matrixes in foodstuffs due to the presence of a high number of moieties with different physical and chemical properties. Glycerolipids include glycerol and two fatty acids esterified in positions sn-1 and sn-2 with higher concentration of unsaturated fatty acids than in the triglyceride fraction of milk. Sphingolipids consist of a sphingoid base linked to a fatty acid across an amide bond. Their amphiphilic nature makes them suitable to be added into a variety of foods and recent investigations show that phospholipids, mainly phosphatidylserine and sphingomyelin, can exert antimicrobial, antiviral, and anticancer activities as well as positive effects in Alzheimer's disease, stress, and memory decline. Polar lipids can be found as natural constituents in the membranes of all living organisms with soybean and eggs as the principal industrial sources, yet they have low contents in phosphatidylserine and sphingomyelin. Animal products are rich sources of these compounds but since there are legal restrictions to avoid transmission of prions, milk and dairy products are gaining interest as alternative sources. This review summarizes the analysis of polar lipids in dairy products including sample preparation (extraction and fractionation/isolation) and analysis by GC or HPLC and the latest research works using ELSD, CAD, and MS detectors. PMID:27610267

  4. Association of anti-phospholipid antibodies with connective tissue diseases

    Directory of Open Access Journals (Sweden)

    Reena Rai

    2015-01-01

    Full Text Available Background: The antiphospholipid antibodies (APLA are directed against phospholipids and their binding proteins and are frequently found in association with connective tissue disorders. Systemic lupus erythematoses (SLE with APLA may cause a diagnostic dilemma as there are several manifestations like haemolytic anemia, thrombocytopenia, neurologic manifestations, leg ulcerations, serositis proteinuria which overlap in both these conditions. We conducted a study to find out the association of antiphospholipid antibodies with connective tissue diseases and compared the clinical and laboratory parameters between antiphoshpolipid antibody positive and antiphoshpolipid antibody negative group. Materials and Methods: This study was carried out in 102 patients diagnosed with connective tissue diseases. APLA testing was done at baseline and for those positive, the test was repeated after 12 weeks. Results: 14.7 % of patients with connective tissue diseases tissue had positive antiphoshpolipid antibodies. Positive antiphoshpolipid antibody was detected in 73.3% of patients with SLE group, 13.3% of patients with mixed connective tissue disease (MCTD and 13.3% of patients with systemic sclerosis. APLA positivity was seen in SLE patients with leg ulcers (87.2%, neurologic manifestation (72.7%, hemolytic anemia (62.3%, thrombocytopenia (72.7%, serositis (27.8% and proteinuria(19.6%. Conclusions: Antiphoshpolipid antibodies should be tested in all patients with connective tissue disease.

  5. Anisotropic metal growth on phospholipid nanodiscs via lipid bilayer expansion

    Science.gov (United States)

    Oertel, Jana; Keller, Adrian; Prinz, Julia; Schreiber, Benjamin; Hübner, René; Kerbusch, Jochen; Bald, Ilko; Fahmy, Karim

    2016-05-01

    Self-assembling biomolecules provide attractive templates for the preparation of metallic nanostructures. However, the intuitive transfer of the “outer shape” of the assembled macromolecules to the final metallic particle depends on the intermolecular forces among the biomolecules which compete with interactions between template molecules and the metal during metallization. The shape of the bio-template may thus be more dynamic than generally assumed. Here, we have studied the metallization of phospholipid nanodiscs which are discoidal particles of ~10 nm diameter containing a lipid bilayer ~5 nm thick. Using negatively charged lipids, electrostatic adsorption of amine-coated Au nanoparticles was achieved and followed by electroless gold deposition. Whereas Au nanoparticle adsorption preserves the shape of the bio-template, metallization proceeds via invasion of Au into the hydrophobic core of the nanodisc. Thereby, the lipidic phase induces a lateral growth that increases the diameter but not the original thickness of the template. Infrared spectroscopy reveals lipid expansion and suggests the existence of internal gaps in the metallized nanodiscs, which is confirmed by surface-enhanced Raman scattering from the encapsulated lipids. Interference of metallic growth with non-covalent interactions can thus become itself a shape-determining factor in the metallization of particularly soft and structurally anisotropic biomaterials.

  6. Visualization and analysis of lipopolysaccharide distribution in binary phospholipid bilayers

    Energy Technology Data Exchange (ETDEWEB)

    Henning, Maria Florencia [Instituto de Investigaciones Bioquimicas La Plata (INIBIOLP), CCT-La Plata, CONICET, Facultad de Ciencias Medicas, UNLP, Calles 60 y 120, 1900 La Plata (Argentina); Sanchez, Susana [Laboratory for Fluorescence Dynamics, University of California-Irvine, Irvine, CA (United States); Bakas, Laura, E-mail: lbakas@biol.unlp.edu.ar [Instituto de Investigaciones Bioquimicas La Plata (INIBIOLP), CCT-La Plata, CONICET, Facultad de Ciencias Medicas, UNLP, Calles 60 y 120, 1900 La Plata (Argentina); Departamento de Ciencias Biologicas, Facultad de Ciencias Exactas, UNLP, Calles 47 y 115, 1900 La Plata (Argentina)

    2009-05-22

    Lipopolysaccharide (LPS) is an endotoxin released from the outer membrane of Gram-negative bacteria during infections. It have been reported that LPS may play a role in the outer membrane of bacteria similar to that of cholesterol in eukaryotic plasma membranes. In this article we compare the effect of introducing LPS or cholesterol in liposomes made of dipalmitoylphosphatidylcholine/dioleoylphosphatidylcholine on the solubilization process by Triton X-100. The results show that liposomes containing LPS or cholesterol are more resistant to solubilization by Triton X-100 than the binary phospholipid mixtures at 4 {sup o}C. The LPS distribution was analyzed on GUVs of DPPC:DOPC using FITC-LPS. Solid and liquid-crystalline domains were visualized labeling the GUVs with LAURDAN and GP images were acquired using a two-photon microscope. The images show a selective distribution of LPS in gel domains. Our results support the hypothesis that LPS could aggregate and concentrate selectively in biological membranes providing a mechanism to bring together several components of the LPS-sensing machinery.

  7. Mixed Micelles made of Poly(ethylene glycol)-Phosphatidylethanolamine Conjugate and D-α-tocopheryl Polyethylene Glycol 1000 Succinate as Pharmaceutical Nanocarriers for Camptothecin

    OpenAIRE

    Mu, L; Elbayoumi, T.A.; Torchilin, V.P.

    2005-01-01

    Micelles from the mixture of poly(ethylene glycol)-phosphatidyl ethanolamine conjugate (PEG-PE) and D-α-tocopheryl polyetheyene glycol 1000 succinate (TPGS) were prepared loaded with the poorly soluble anticancer drug camptothecin (CPT). The solubilization of CPT by the mixed micelles was more efficient than with earlier described micelles made of PEG-PE alone. CPT-loaded mixed micelles were stable upon storage and dilution and firmly retained the incorporated drug. The cytotoxicity of the CP...

  8. pH and ionic strength responsive polyelectrolyte block copolymer micelles prepared by ring opening metathesis polymerization

    NARCIS (Netherlands)

    Stubenrauch, K.; Voets, I.K.; Popovski, G.F.; Trimmel, G.

    2009-01-01

    Well-defined amphiphilic block copolymers were prepared by ring opening metathesis polymerization and their stimuli responsive behavior of formed micelles in aqueous solution was investigated. The hydrophobic core of the micelles consists of either a poly[5,6-bis(ethoxymethyl)bicyclo[2.2.1]hept-2-en

  9. pH-Responsive Hyaluronic Acid-Based Mixed Micelles for the Hepatoma-Targeting Delivery of Doxorubicin

    Directory of Open Access Journals (Sweden)

    Jing-Liang Wu

    2016-03-01

    Full Text Available The tumor targetability and stimulus responsivity of drug delivery systems are crucial in cancer diagnosis and treatment. In this study, hepatoma-targeting mixed micelles composed of a hyaluronic acid–glycyrrhetinic acid conjugate and a hyaluronic acid-l-histidine conjugate (HA–GA/HA–His were prepared through ultrasonic dispersion. The formation and characterization of the mixed micelles were confirmed via 1H-NMR, particle size, and ζ potential measurements. The in vitro cellular uptake of the micelles was evaluated using human liver carcinoma (HepG2 cells. The antitumor effect of doxorubicin (DOX-loaded micelles was investigated in vitro and in vivo. Results indicated that the DOX-loaded HA–GA/HA–His micelles showed a pH-dependent controlled release and were remarkably absorbed by HepG2 cells. Compared with free DOX, the DOX-loaded HA–GA/HA–His micelles showed a higher cytotoxicity to HepG2 cells. Moreover, the micelles effectively inhibited tumor growth in H22 cell-bearing mice. These results suggest that the HA–GA/HA–His mixed micelles are a good candidate for drug delivery in the prevention and treatment of hepatocarcinoma.

  10. A small-angle neutron scattering study of sodium dodecyl sulfate-poly(propylene oxide) methacrylate mixed micelles.

    Science.gov (United States)

    Bastiat, Guillaume; Grassl, Bruno; Borisov, Oleg; Lapp, Alain; François, Jeanne

    2006-03-15

    Mixed micelle of protonated or deuterated sodium dodecyl sulfate (SDS and SDSd25, respectively) and poly(propylene oxide) methacrylate (PPOMA) are studied by small-angle neutron scattering (SANS). In all the cases the scattering curves exhibit a peak whose position changes with the composition of the system. The main parameters which characterize mixed micelles, i.e., aggregation numbers of SDS and PPOMA, geometrical dimensions of the micelles and degree of ionisation are evaluated from the analysis of the SANS curves. The position q(max) of the correlation peak can be related to the average aggregation numbers of SDS-PPOMA and SDSd25-PPOMA mixed micelles. It is found that the aggregation number of SDS decreases upon increasing the weight ratio PPOMA/SDS (or SDSd25). The isotopic combination, which uses the "contrast effect" between the two micellar systems, has allowed us to determine the mixed micelle composition. Finally, the SANS curves were adjusted using the RMSA for the structure factor S(q) of charged spherical particles and the form factor P(q) of spherical core-shell particle. This analysis confirms the particular core-shell structure of the SDS-PPOMA mixed micelle, i.e., a SDS "core" micelle surrounded by the shell formed by PPOMA macromonomers. The structural parameters of mixed micelles obtained from the analysis of the SANS data are in good agreement with those determined previously by conductimetry and fluorescence studies.

  11. Specific pools of phospholipids are used for lipoprotein secretion by cultured rat hepatocytes

    International Nuclear Information System (INIS)

    The role of phospholipid biosynthesis in lipoprotein secretion from cultured rat hepatocytes has been investigated. In liver, phosphatidylcholine (PC) is made both by the CDP-choline pathway and by the methylation of phosphatidyl-ethanolamine (PE), which in turn is derived from both serine (via phosphatidylserine) and ethanolamine (via CDP-ethanol-amine). Monolayer cultures of rat hepatocytes were incubated in the presence of [methyl-3H]choline, [2-3H]ethanolamine or [3-3H]serine. The specific radioactivity of the phospholipids derived from each of these precursors was measured in the cells and in the secreted lipoproteins of the culture medium. The specific radioactivities of PC and PE derived from [1-3H]ethanolamine were markedly lower (approximately 1/2 and less than 1/10, respectively) in the secreted phospholipids than in the cellular phospholipids. Thus, ethanolamine was not an effective precursor of the phospholipids in lipoproteins. On the contrary, the specific radioactivity of PC made from [methyl-3H]choline was approximately equal in cells and lipoproteins. In addition, over the first 4 h of incubation with [3-3H]serine, the specific radioactivities of PC and PE were significantly higher in the lipoproteins than in the cells. These data indicate that specific pools of phospholipids are selected on the basis of their routes of biosynthesis, for secretion into lipoproteins

  12. Regulation of phospholipid synthesis in phosphatidylserine synthase-deficient (chol) mutants of Saccharomyces cerevisiae

    International Nuclear Information System (INIS)

    Saccharomyces cerevisiae mutants, chol, are deficient in the synthesis of the phospholipid phosphatidylserine owing to lowered activity of the membrane-associated enzyme phosphatidylserine synthase. These mutants are auxotrophic for ethanolamine or choline and, in the absence of these supplements, cannot synthesize phosphatidylethanolamine or phosphatidylcholine (PC). The authors exploited these characteristics of the chol mutants to examine the regulation of phospholipid metabolism in S. cerevisiae. Macromolecular synthesis and phospholipid metabolism were examined in chol cells starved for ethanolamine. Coupled to the decline in PC biosynthesis was a simultaneous decrease in the overall rate of phospholipid synthesis. In particular, the rate of synthesis of phosphatidylinositol decreased in parallel with the decline in PC biosynthesis. However, under conditions of ethanolamine deprivation in chol cells, the cytoplasmic enzyme inositol-1-phosphate synthase could not be repressed by exogenous inositol, and the endogenous synthesis of the phospholipid precursor inositol appeared to be elevated. The implications of these findings with respect to the coordinated regulation of phospholipid synthesis are discussed

  13. Influence of molecular packing and phospholipid type on rates of cholesterol exchange

    International Nuclear Information System (INIS)

    The rates of [14C]cholesterol transfer from small unilamellar vesicles containing cholesterol dissolved in bilayers of different phospholipids have been determined to examine the influence of phospholipid-cholesterol interactions on the rate of cholesterol desorption from the lipid-water interface. At 370C, for vesicles containing 10 mol % cholesterol, the half-times for exchange are about 1, 13, and 80 h, respectively, for unsaturated PC, saturated PC, and SM. In order to probe how differences in molecular packing in the bilayers cause the rate constants for cholesterol desorption to be in the order unsaturated PC > saturated PC > SM, nuclear magnetic resonance (NMR) and monolayer methods were used to evaluate the cholesterol physical state and interactions with phospholipid. The NMR relaxation parameters for [4-13C] cholesterol reveal no differences in molecular dynamics in the above bilayers. The greater van der Waals interaction in the SM monolayer (or bilayer) compared to PC gives rise to a larger condensation by cholesterol. This is a direct demonstration of the greater interaction of cholesterol with SM compared to PC. An estimate of the van der Waals interactions between cholesterol and these phospholipids has been used to derive a relationship between the ratio of the rate constants for cholesterol desorption and the relative molecular areas (lateral packing density) in two bilayers. This analysis suggests that differences in cholesterol-phospholipid van der Waals interaction energy are an important cause of varying rates of cholesterol exchange from different host phospholipid bilayers

  14. Reverse micelles extraction of nattokinase: From model system to real system

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Nattokinase is a novel fibrinolytic enzyme, which is homologous to Subtilisin Carlsberg. In this paper, Subtilisin Carlsberg was taken as a model protein of nattokinase. Effects of pH, ionic strength, concentration of isopropanol on the extraction of Subtilisin Carlsberg with AOT/isooctane reverse micelles system were investigated. Further, the process of reverse micelles extraction of nattokinase from fermentation broth was studied. By taking the reverse micelles of AOT/isooctane as extractant to perform a full extraction cycle, it was found that about eighty percent of the total activity of nattokinase in the fermentation broth could be recovered and the purification factor was about 2.5. Homologous protein could be reasonably used as model protein of a target protein.

  15. Activity and stability of yeast alcohol dehydrogenase (YADH) entrapped in aerosol OT reverse micelles.

    Science.gov (United States)

    Sarcar, S; Jain, T K; Maitra, A

    1992-02-20

    The activity and stability of yeast alcohol dehydrogenase (YADH) entrapped in aerosol OT reverse micellar droplets have been investigated spectrophotometrically. Various physical parameters, e.g., water pool size, w(0), pH, and temperature, were optimized for YADH in water/AOT/isooctane reverse micelles. It was found that the enzyme exhibits maximum activity at w(0) = 28 and pH 8.1. It was more active in reverse micelles than in aqueous buffers at a particular temperature and was denatured at about 307 degrees C in both the systems. At a particular temperature YADH entrapped in reverse micelles was less stable than when it was dissolved in aqueous buffer.

  16. Pharmacokinetic considerations in the development of labeled liposomes and micelle for diagnostic imaging

    Energy Technology Data Exchange (ETDEWEB)

    Torchilin, V. P. [Massachusetts General Hospital, Boston (United States). Center for Imaging and Pharmaceutical Research]|[Harvard Medical School, Boston (United States)

    1997-06-01

    The current status of application of liposomes and micelles as carriers for diagnostic imaging agents in experimental and clinical medicine is considered. Liposomes and micelles loaded with appropriate contrast agents have been shown to be suitable for all imaging modalities, including gamma-, magnetic resonance (MR) and computed tomography (CT). The methods are briefly described to prepare liposomes loaded with various contrast agents, as well as some basic data on their in vitro and in vivo properties and biodistribution. The application of contrast-loaded liposomes in different modalities for the experimental and clinical imaging of various organs, tissues, and pathological conditions is briefly reviewed. New trends in the preparation and use of contrast-loaded liposomes and micelles are also considered, such as the application of amphiphilic polychelating polymers and polymers for steric protection of micro particulate pharmaceutical carriers.

  17. The effect of PEO block lengths on the size and stability of complex coacervate core micelles.

    Science.gov (United States)

    Adams, Dave J; Rogers, Sue H; Schuetz, Peter

    2008-06-15

    We report on a series of polyion complexes from mixtures of poly(ethylene oxide)-block-poly(N,N-diethylaminoethylmethacrylate) (PEO-PDEAMA) and poly(ethylene oxide)-block-poly(aspartic acid) (PEO-PAsp). As expected, the micelle size, polydispersity and stability are dependant on the relative and absolute lengths of the polyelectrolyte chains. However, we also demonstrate that whilst the length of the charged polyelectrolyte blocks is important, the length of the PEO chains is an equally relevant variable in determining both the size and stability of the final micelles as well as the degree of charge neutralisation at which micellisation occurs. We also show that the kinetics of formation can result in very different stability of the final micelles.

  18. Dissolution and enzymatic hydrolysis of casein micelles studied by dynamic light scattering

    Institute of Scientific and Technical Information of China (English)

    LIU Rui; QI Wei; SU Rongxin; ZHANG Yubin; JIN Fengmin; HE Zhimin

    2007-01-01

    The effects of temperature,ionic strength,and enzymatic hydrolysis on the average hydrodynamic radius (Rh) of casein micelles in phosphate buffer were studied by using dynamic light scattering.The results showed that the average Rh value of casein mieelles decreased irreversibly during the heating,decreased with the increase of ionic strength in lower ionic strength solution (less than 0.05 tool/L),but opposite in higher ionic strength solution (above 0.1 tool/L).The Rh value of casein increased rapidly during the process of enzymatic hydrolysis,and the structural model of casein micelles in the enzymatic hydrolysis process was also proposed,i.e.the casein micelle changed from compact sphere into unfolded and regularly flocky peptides.

  19. Biocompatible Polyhydroxyethylaspartamide-based Micelles with Gadolinium for MRI Contrast Agents

    Directory of Open Access Journals (Sweden)

    Kim Hyo Jeong

    2010-01-01

    Full Text Available Abstract Biocompatible poly-[N-(2-hydroxyethyl-d,l-aspartamide]-methoxypoly(ethyleneglycol-hexadecylamine (PHEA-mPEG-C16 conjugated with 1,4,7,10-tetraazacyclododecan-1,4,7,10-tetraacetic acid-gadolinium (DOTA-Gd via ethylenediamine (ED was synthesized as a magnetic resonance imaging (MRI contrast agent. Amphiphilic PHEA-mPEG-C16-ED-DOTA-Gd forms micelle in aqueous solution. All the synthesized materials were characterized by proton nuclear magnetic resonance (1H NMR. Micelle size and shape were examined by dynamic light scattering (DLS and atomic force microscopy (AFM. Micelles with PHEA-mPEG-C16-ED-DOTA-Gd showed higher relaxivities than the commercially available gadolinium contrast agent. Moreover, the signal intensity of a rabbit liver was effectively increased after intravenous injection of PHEA-mPEG-C16-ED-DOTA-Gd.

  20. Uniform patchy and hollow rectangular platelet micelles from crystallizable polymer blends

    Science.gov (United States)

    Qiu, Huibin; Gao, Yang; Boott, Charlotte E.; Gould, Oliver E. C.; Harniman, Robert L.; Miles, Mervyn J.; Webb, Stephen E. D.; Winnik, Mitchell A.; Manners, Ian

    2016-05-01

    The preparation of colloidally stable, self-assembled materials with tailorable solid or hollow two-dimensional (2D) structures represents a major challenge. We describe the formation of uniform, monodisperse rectangular platelet micelles of controlled size by means of seeded-growth methods that involve the addition of blends of crystalline-coil block copolymers and the corresponding crystalline homopolymer to cylindrical micelle seeds. Sequential addition of different blends yields solid platelet block comicelles with concentric rectangular patches with distinct coronal chemistries. These complex nano-objects can be subject to spatially selective processing that allows their disassembly to form perforated platelets, such as well-defined hollow rectangular rings. The solid and hollow 2D micelles provide a tunable platform for further functionalization and potential for a variety of applications.

  1. Hyperbranched polycarbonate-based multimolecular micelle with enhanced stability and loading efficiency.

    Science.gov (United States)

    Su, Wei; Luo, Xiao-Hua; Wang, Hua-Fen; Li, Lei; Feng, Jun; Zhang, Xian-Zheng; Zhuo, Ren-Xi

    2011-02-16

    We herein develop a facile catalyst-free method to prepare hyperbranched hydroxyl-enriched aliphatic polycarbonate according to SCROP strategy. PEG-attached multiarm hyperbranched copolymer HEHDO-star-mPEG was further designed. It was found that HEHDO-star-mPEG can self-assemble into supramolecular multimolecular micelles in water. HEHDO-star-mPEG micelle showed excellent stability with respect to micellar size upon dilution, and displayed good cell-biocompatibility. An anticancer drug of doxorubicin with hydrogen-bonding functionality was incorporated into obtained micelles to establish a drug delivery system model. A high drug-loading content as well as sustained release pattern for HEHDO-star-mPEG based delivery system was achieved.

  2. Biocompatible Polyhydroxyethylaspartamide-based Micelles with Gadolinium for MRI Contrast Agents

    Science.gov (United States)

    Jeong, Sang Young; Kim, Hyo Jeong; Kwak, Byung-Kook; Lee, Ha-Young; Seong, Hasoo; Shin, Byung Cheol; Yuk, Soon Hong; Hwang, Sung-Joo; Cho, Sun Hang

    2010-12-01

    Biocompatible poly-[ N-(2-hydroxyethyl)- d, l-aspartamide]-methoxypoly(ethyleneglycol)-hexadecylamine (PHEA-mPEG-C16) conjugated with 1,4,7,10-tetraazacyclododecan-1,4,7,10-tetraacetic acid-gadolinium (DOTA-Gd) via ethylenediamine (ED) was synthesized as a magnetic resonance imaging (MRI) contrast agent. Amphiphilic PHEA-mPEG-C16-ED-DOTA-Gd forms micelle in aqueous solution. All the synthesized materials were characterized by proton nuclear magnetic resonance (1H NMR). Micelle size and shape were examined by dynamic light scattering (DLS) and atomic force microscopy (AFM). Micelles with PHEA-mPEG-C16-ED-DOTA-Gd showed higher relaxivities than the commercially available gadolinium contrast agent. Moreover, the signal intensity of a rabbit liver was effectively increased after intravenous injection of PHEA-mPEG-C16-ED-DOTA-Gd.

  3. Polymerization of o-Phenylenediamine Catalyzed by Hemeproteins Encapsulated in Reversed Micelle

    Institute of Scientific and Technical Information of China (English)

    YANG Yong; MAO Lu-yuan; LI Liu-zhu; LIU Xiao-guang; SHI Jun; CAO Shao-kui

    2004-01-01

    Hemeproteins encapsulated in reversed micelle formulated with di-2-ethylhexyl sulfosuccinate (AOT)was found to catalyze the polymerization of o-phenylenediamine (o-PDA) with hydrogen peroxide, whereas o-PDA catalyzed by hemeproteins dissolved in water could only form its trimers. As the nanostructural environment in reversed micelle acts as a certain orientation surrounding medium, it offers a strong electrostatic field that alters the reductive potential of Fe3+/Fe2+ (Em7) in the heme of hemeproteins and thus increases the catalytic activity of peroxidase accordingly. According to the results of UV-Vis, 1H NMR and FTIR, the polymer catalyzed by hemoglobin(Hb) in reversed micelle was presumed to be constructed of lines and trapeziforms alternatively.

  4. Formation of reverse micelles in supercritical carbon dioxide and its thermodynamics

    Institute of Scientific and Technical Information of China (English)

    WEN Zhen; DANG Zhi; ZONG Minhua; ZHU Zhixin

    2007-01-01

    The solubilization behavior of methyl orange as a solvation probe in multiple systems composed of supercritical carbon dioxide,surfactants and co-solvents,is studied.It is coneluded that some surfactants,such as sodium bis-(2-ethylhexyl)sulfosuccinate(AOT)and isooctyl phenol polyethoxylate (TX-10),could form reverse micelles in supercritical carbon dioxide under the action of butanol.The formation of reverse micelles is a spontaneous process thermodynamically.Specifically for the nonionic surfactant TX-10,the formation of reverse micelles is dependent on the entropy increase in the system,while for the anionic surfactant AOT,the micellization is mainly dominated by the increase in enthalpy at higher temperatures,but by the increase in entropy at lower temperatures.

  5. Improving aqueous solubility and antitumor effects by nanosized gambogic acid-mPEG2000 micelles

    Directory of Open Access Journals (Sweden)

    Cai LL

    2013-12-01

    Full Text Available Lulu Cai,1,* Neng Qiu,2,* Mingli Xiang,3,* Rongsheng Tong,1 Junfeng Yan,1 Lin He,1 Jianyou Shi,1 Tao Chen,4 Jiaolin Wen,3 Wenwen Wang,3 Lijuan Chen31Department of Pharmacy, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, 2College of Materials and Chemistry and Chemical Engineering, Chengdu University of Technology, 3State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China; 4Faculty of Pharmacy, University of Montreal, Montreal, QC, Canada *These authors contributed equally to this paperAbstract: The clinical application of gambogic acid, a natural component with promising antitumor activity, is limited due to its extremely poor aqueous solubility, short half-life in blood, and severe systemic toxicity. To solve these problems, an amphiphilic polymer-drug conjugate was prepared by attachment of low molecular weight (ie, 2 kDa methoxy poly(ethylene glycol methyl ether (mPEG to gambogic acid (GA-mPEG2000 through an ester linkage and characterized by 1H nuclear magnetic resonance. The GA-mPEG2000 conjugates self-assembled to form nanosized micelles, with mean diameters of less than 50 nm, and a very narrow particle size distribution. The properties of the GA-mPEG2000 micelles, including morphology, stability, molecular modeling, and drug release profile, were evaluated. MTT (3-(4,5-dimethylthiazol-2-yl-2,5 diphenyl tetrazolium bromide tests demonstrated that the GA-mPEG2000 micelle formulation had obvious cytotoxicity to tumor cells and human umbilical vein endothelial cells. Further, GA-mPEG2000 micelles were effective in inhibiting tumor growth and prolonged survival in subcutaneous B16-F10 and C26 tumor models. Our findings suggest that GA-mPEG2000 micelles may have promising applications in tumor therapy.Keywords: gambogic acid, poly(ethylene glycol-drug conjugate, micelle, antitumor, toxicity

  6. A biocompatible cobaltporphyrin-based complex micelle constructed via supramolecular assembly for oxygen transfer.

    Science.gov (United States)

    Shen, Liangliang; Qu, Rui; Shi, Hejin; Huang, Fan; An, Yingli; Shi, Linqi

    2016-05-26

    Herein, a complex micelle as an oxygen nano-carrier is constructed through the hierarchical assembly of the diblock copolymer poly(ethylene glycol)-block-poly(l-lysine) (PEG-b-PLys), tetrakis(4-sulfonatophenyl)porphinato cobalt(ii) (Co(ii)TPPS), a heptapeptide (Cys-His-His-His-His-His-His) and heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin (TM-β-CD). Co(ii)TPPS was encapsulated into the cavities of TM-β-CDs driven by the host-guest interaction so that the irreversible formation of a μ-oxo-dimer of Co(ii)TPPS can be effectively prevented. The imidazole groups of the heptapeptide were selected as good axial ligands coordinating to the centric cobalt of Co(ii)TPPS, which subtly constituted the five-coordinated precursor serving as an active functional centre for oxygen binding. The sixth position of Co(ii)TPPS can bind oxygen. Furthermore, the host-guest inclusion (TM-β-CD/Co(ii)TPPS) was loaded into the hydrophobic core of the complex micelle and tightly fixed with PLys chains. The hydrophilic PEG blocks stretched in the aqueous solution constitute the shells which stabilize the structure of the complex micelle as well as impart the complex micelle sufficient blood circulation time. Moreover, the complex micelle exhibited excellent biocompatibility and cellular uptake. Therefore, the rationally designed amphiphilic structure can work as promising artificial O2 carriers in vivo. Potentially, the complex micelle can be expected to change the anaerobic microenvironment and find applications in the repair of the cells damaged by cellular hypoxia. PMID:27009911

  7. Efficient gene delivery system mediated by cis-aconitate-modified chitosan-g-stearic acid micelles

    Directory of Open Access Journals (Sweden)

    Yao JJ

    2014-06-01

    Full Text Available Jing-Jing Yao, Yong-Zhong Du, Hong Yuan, Jian You, Fu-Qiang HuCollege of Pharmaceutical Sciences, Zhejiang University, Hangzhou, People’s Republic of ChinaAbstract: Cis-aconitate-modified chitosan-g-stearic acid (CA-CSO-SA micelles were ­synthesized in this study to improve the gene transfection efficiency of chitosan-g-stearic acid (CSO-SA. The CA-CSO-SA micelles had a similar size, critical micelle concentration, and ­morphology, but their zeta potential and cytotoxicity were reduced compared with CSO-SA micelles. After modification with cis-aconitate, the CA-CSO-SA micelles could also compact plasmid DNA (pDNA to form nanocomplexes. However, the DNA binding ability of CA-CSO-SA was slightly reduced compared with that of CSO-SA. The transfection efficiency mediated by CA-CSO-SA/pDNA against HEK-293 cells reached up to 37%, and was much higher than that of CSO-SA/pDNA (16%. Although the cis-aconitate modification reduced cellular uptake kinetics in the initial stages, the total amount of cellular uptake tended to be the same after 24 hours of incubation. An endocytosis inhibition experiment showed that the internalization mechanism of CA-CSO-SA/pDNA in HEK-293 cells was mainly via clathrin-mediated endocytosis, as well as caveolae-mediated endocytosis and macropinocytosis. Observation of intracellular trafficking indicated that the CSO-SA/pDNA complexes were trapped in endolysosomes, but CA-CSO-SA/pDNA was more widely distributed in the cytosol. This study suggests that modification with cis-aconitate improves the transfection efficiency of CSO-SA/pDNA.Keywords: chitosan-g-stearic acid, cis-aconitate, micelles, transfection efficiency, intracellular trafficking

  8. Amphiphilic polymeric micelle as pseudostationary phase in electrokinetic chromatography for analysis of eight corticosteroids in cosmetics.

    Science.gov (United States)

    Xu, Xiaojin; Ni, Xinjiong; Cao, Yuhua; Zhuo, Xiaolu; Yang, Xiaoxiao; Cao, Guangqun

    2014-03-01

    Amphiphilic polymeric micelle, as a novel pseudostationary phase in EKC was used to determine eight kinds of corticosteroids namely hydrocortisone, prednisolone, hydrocortisone acetate, prednisone, cortisone acetate, prednisolone acetate, dexamethasone, and triamcinolone acetonide in cosmetics. Amphiphilic random copolymer poly(methyl methacrylate-co-methacrylic acid) (P(MMA-co-MAA)) was micellizated via neutralization in alkaline aqueous solution. The influences of the molar ratio of monomer MMA to MAA, the concentration of polymer and pH on the polymeric micelle microstructure and EKC performances were investigated. As molar ratio of MMA to MAA in P(MMA-co-MAA) increased, both CMC and environmental polarity of the inner core in polymeric micelle decreased dramatically. With increasing monomer ratio, the size of polymeric micelles increased firstly, and then decreased, finally increased again. ζ potential of the micelle had a slight decline trend. As increment of polymer concentration, the size of the polymeric micelle increased steadily. By optimizing the monomer ratio, the polymer concentration, and pH of the running buffer, as well as operation conditions such as separation voltage and temperature, the eight analytes could be separated within 16.5 min using 7.5 mg/mL polymer with the monomer ratio of 7:3 dissolved in pH 9.2 borax buffer as the running buffer. The method has been used for analysis of corticosteroids in cosmetic samples with simple extraction; the recoveries for eight analytes were between 85.9 and 106%. This method was of accuracy, repeatability, pretreatment simplicity, and could be applied to the quality control of cosmetics. PMID:24338855

  9. Biodegradable micelles enhance the antiglioma activity of curcumin in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Zheng S

    2016-06-01

    Full Text Available Songping Zheng,1,* Xiang Gao,1,2,* Xiaoxiao Liu,1 Ting Yu,1 Tianying Zheng,1 Yi Wang,1 Chao You1 1Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, People’s Republic of China; 2Department of Pharmacology, Yale School of Medicine, Yale University, New Haven, CT, USA *These authors contributed equally to this work Abstract: Curcumin (Cur, a natural polyphenol of Curcuma longa, has been recently reported to possess antitumor activities. However, due to its poor aqueous solubility and low biological availability, the clinical application of Cur is quite limited. The encapsulation of hydrophobic drugs into nanoparticles is an effective way to improve their pharmaceutical activities. In this research, nanomicelles loaded with Cur were formulated by a self-assembly method with biodegradable monomethoxy poly(ethylene glycol-poly(lactide copolymers (MPEG-PLAs. After encapsulation, the cellular uptake was increased and Cur could be released from MPEG-PLA micelles in a sustained manner. The Cur-loaded MPEG-PLA micelles (Cur/MPEG-PLA micelles exhibited an enhanced toxicity on C6 and U251 glioma cells and induced more apoptosis on C6 glioma cells compared with free Cur. Moreover, the therapy efficiency of Cur/MPEG-PLA micelles was evaluated at length on a nude mouse model bearing glioma. The Cur/MPEG-PLA micelles were more effective on suppressing tumor growth compared with free Cur, which indicated that Cur/MPEG-PLA micelles improved the antiglioma activity of Cur in vivo. The results of immunohistochemical and immunofluorescent analysis indicated that the induction of apoptosis, antiangiogenesis, and inhibition of cell proliferation may contribute to the improvement in antiglioma effects. Our data suggested that Cur/MPEG-PLA may have potential clinic applications in glioma therapy. Keywords: curcumin, glioma, cell apoptosis, cell proliferation, angiogenesis 

  10. Photorheologically reversible micelle composed of polymerizable cationic surfactant and 4-phenylazo benzoic acid☆

    Institute of Scientific and Technical Information of China (English)

    Jie Chen; Bo Fang; Hao Jin; Licheng Yu; Meng Tian; Kejing Li; Leiping Jin; Mo Yang

    2016-01-01

    A photorheologically reversible micelle composed of polymerizable cationic surfactant n-cetyl dimethylallyl am-monium chloride (CDAAC) and trans-4-phenylazo benzoic acid (trans-ACA) was prepared. The effects of molar ratio of CDAAC/trans-ACA, time of UV and visible light irradiation and temperature on the rheological properties of micellar system were investigated. The results show that before UV irradiation the system with an optimum CDAAC/trans-ACA molar ratio of 1.4 forms viscoelastic micelles at 45 °C. After 365 nm UV irradiation, the viscos-ities of micel e systems with different concentrations at fixed molar ratio of 1.4 are decreased by 85%–95%. The CDAAC/trans-ACA (14 mmol·L−1/10 mmol·L−1) micel e system exhibits shear thinning property and its viscos-ity is decreased obviously with the increases of UV irradiation time less than 1 h. The rheological process during UV irradiation for CDAAC/trans-ACA (14 mmol·L−1/10 mmol·L−1) micelle proves that viscosity, elastic modulus G′and viscous modulus G″will reduce quickly with the UV light. Furthermore, the micelle system after 1 h UV-irradiation is able to revert to its initial high viscosity with 460 nm visible light irradiation for 4 h, and the micelle can be cycled between low and high viscosity states by repetitive UV and visible light irradiations. The UV–Vis spectra of CDAAC/trans-ACA micelle indicate that its photosensitive rheological properties are related closely to photoisomerization of trans-ACA to cis-ACA.

  11. Cisplatin-loaded core cross-linked micelles: comparative pharmacokinetics, antitumor activity, and toxicity in mice

    Directory of Open Access Journals (Sweden)

    Oberoi HS

    2012-06-01

    Full Text Available Hardeep S Oberoi,1 Natalia V Nukolova,1,2 Frederic C Laquer,3 Larisa Y Poluektova,4 Jiangeng Huang,1 Yazen Alnouti,1 Masanao Yokohira,5 Lora L Arnold,5 Alexander V Kabanov,1,2 Samuel M Cohen,5 Tatiana K Bronich,1,21Department of Pharmaceutical Sciences and Center for Drug Delivery and Nanomedicine, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, USA; 2Department of Chemistry, MV Lomonosov Moscow State University, Leninskie Gory, Moscow, Russia; 3Department of Chemistry, University of Nebraska at Omaha, 4Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, 5Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USAAbstract: Polymer micelles with cross-linked ionic cores are shown here to improve the therapeutic performance of the platinum-containing anticancer compound cisplatin. Biodistribution, antitumor efficacy, and toxicity of cisplatin-loaded core cross-linked micelles of poly(ethylene glycol-b-poly(methacrylic acid were evaluated in a mouse ovarian cancer xenograft model. Cisplatin-loaded micelles demonstrated prolonged blood circulation, increased tumor accumulation, and reduced renal exposure. Improved antitumor response relative to free drug was seen in a mouse model. Toxicity studies with cisplatin-loaded micelles indicate a significantly improved safety profile and lack of renal abnormalities typical of free cisplatin treatment. Overall, the study supports the fundamental possibility of improving the potential of platinum therapy using polymer micelle-based drug delivery.Keywords: cross-linked micelle, cisplatin, ovarian cancer, block ionomer complex, drug delivery

  12. Amphiphilic polymeric micelle as pseudostationary phase in electrokinetic chromatography for analysis of eight corticosteroids in cosmetics.

    Science.gov (United States)

    Xu, Xiaojin; Ni, Xinjiong; Cao, Yuhua; Zhuo, Xiaolu; Yang, Xiaoxiao; Cao, Guangqun

    2014-03-01

    Amphiphilic polymeric micelle, as a novel pseudostationary phase in EKC was used to determine eight kinds of corticosteroids namely hydrocortisone, prednisolone, hydrocortisone acetate, prednisone, cortisone acetate, prednisolone acetate, dexamethasone, and triamcinolone acetonide in cosmetics. Amphiphilic random copolymer poly(methyl methacrylate-co-methacrylic acid) (P(MMA-co-MAA)) was micellizated via neutralization in alkaline aqueous solution. The influences of the molar ratio of monomer MMA to MAA, the concentration of polymer and pH on the polymeric micelle microstructure and EKC performances were investigated. As molar ratio of MMA to MAA in P(MMA-co-MAA) increased, both CMC and environmental polarity of the inner core in polymeric micelle decreased dramatically. With increasing monomer ratio, the size of polymeric micelles increased firstly, and then decreased, finally increased again. ζ potential of the micelle had a slight decline trend. As increment of polymer concentration, the size of the polymeric micelle increased steadily. By optimizing the monomer ratio, the polymer concentration, and pH of the running buffer, as well as operation conditions such as separation voltage and temperature, the eight analytes could be separated within 16.5 min using 7.5 mg/mL polymer with the monomer ratio of 7:3 dissolved in pH 9.2 borax buffer as the running buffer. The method has been used for analysis of corticosteroids in cosmetic samples with simple extraction; the recoveries for eight analytes were between 85.9 and 106%. This method was of accuracy, repeatability, pretreatment simplicity, and could be applied to the quality control of cosmetics.

  13. 阴离子蠕虫胶束%Anionic Wormlike Micelles

    Institute of Scientific and Technical Information of China (English)

    赵剑曦; 谢丹华

    2012-01-01

    The molecular geometry and the driving factor of Gibbs free energy are acted as the preconditions for wormlike micelle construction. Bearing this in mind, the formation and properties of the wormlike micelles by conventional anionic surfactants are summarized. The reasons restricting the wormlike micelle formation and high viscoelasticity in conventional anionic surfactant systems are illustrated. The molecular structure advantage of Gemini surfactant in forming wormlike micelles is introduced. Recent advances in anionic wormlike micelle construction, especially for those formed by anionic Gemini surfactants with long and rigid spacer are described in detail. Finally, as a conclusion, it is specially pointed out that based on the superiority of novel molecular structures, Gemini surfactants could become main candidates in constructing wormlike micelles.%本文从分析蠕虫胶束形成的分子几何条件和自由能驱动因素入手,总结了传统阴离子表面活性剂蠕虫胶束的形成和性质,指出制约其构筑和产生优良黏弹性的原因。在此基础上,介绍了Gemini表面活性剂构筑蠕虫胶束的分子结构优势,以及由此构筑阴离子蠕虫胶束的研究进展,尤其是长刚性联接链Gemini表面活性剂形成的蠕虫胶束。最后特别指出,基于新颖分子结构优势,Gemini表面活性剂可望成为蠕虫胶束构筑的主要分子对象。

  14. Growth Behavior, Geometrical Shape, and Second CMC of Micelles Formed by Cationic Gemini Esterquat Surfactants.

    Science.gov (United States)

    Bergström, L Magnus; Tehrani-Bagha, Alireza; Nagy, Gergely

    2015-04-28

    Micelles formed by novel gemini esterquat surfactants have been investigated with small-angle neutron scattering (SANS). The growth behavior of the micelles is found to differ conspicuously depending on the length of the gemini surfactant spacer group. The gemini surfactant with a long spacer form rather small triaxial ellipsoidal tablet-shaped micelles that grow weakly with surfactant concentration in the entire range of measured concentrations. Geminis with a short spacer, on the other hand, form weakly growing oblates or tablets at low concentrations that start to grow much more strongly into polydisperse rodlike or wormlike micelles at higher concentrations. The latter behavior is consistent with the presence of a second CMC that marks the transition from the weakly to the strongly growing regime. It is found that the growth behavior in terms of aggregation number as a function of surfactant concentration always appear concave in weakly growing regimes, while switching to convex behavior in strongly growing regimes. As a result, we are able to determine the second CMC of the geminis with short spacer by means of suggesting a rather precise definition of it, located at the point of inflection of the growth curve that corresponds to the transition from concave to convex growth behavior. Our SANS results are rationalized by comparison with the recently developed general micelle model. In particular, this theory is able to explain and reproduce the characteristic appearances of the experimental growth curves, including the presence of a second CMC and the convex strongly growing regime beyond. By means of optimizing the agreement between predictions from the general micelle model and results from SANS experiments, we are able to determine the three bending elasticity constants spontaneous curvature, bending rigidity, and saddle-splay constant for each surfactant. PMID:25835031

  15. Supersaturation induced by Itraconazole/Soluplus® micelles provided high GI absorption in vivo

    Directory of Open Access Journals (Sweden)

    Yue Zhong

    2016-04-01

    Full Text Available To investigate the effect of supersaturation induced by micelle formation during dissolution on the bioavailability of itraconazole (ITZ/Soluplus® solid dispersion. Solid dispersions prepared by hot melt extrusion (HME were compressed into tablets directly with other excipients. Dissolution behavior of ITZ tablets was studied by dissolution testing and the morphology of micelles in dissolution media was studied using transmission electron microscopy (TEM. Drug transferring from stomach into intestine was simulated to obtain a supersaturated drug solution. Bioavailability studies were performed on the ITZ tablets and Sporanox® in beagle dogs. The morphology of micelles in the dissolution media was observed to be spherical in shape, with an average size smaller than 100 nm. The supersaturated solutions formed by Soluplus® micelles were stable and no precipitation took place over a period of 180 min. Compared with Sporanox®, ITZ tablets exhibited a 2.50-fold increase in the AUC(0–96 of ITZ and a 1.95-fold increase in its active metabolite hydroxyitraconazole (OH-ITZ in the plasma of beagle dogs. The results obtained provided clear evidence that not only the increase in the dissolution rate in the stomach, but also the supersaturation produced by micelles in the small intestine may be of great assistance in the successful development of poorly water-soluble drugs. The micelles formed by Soluplus® enwrapped the molecular ITZ inside the core which promoted the amount of free drug in the intestinal cavity and carried ITZ through the aqueous boundary layer (ABL, resulting in high absorption by passive transportation across biological membranes. The uptake of intact micelles through pinocytosis together with the inhibition of P-glycoprotein-mediated drug efflux in intestinal epithelia contributed to the absorption of ITZ in the gastrointestinal tract. These results indicate that HME with Soluplus®, which can induce supersaturation by micelle

  16. Hydrogen-bonded multilayers of micelles of a dually responsive dicationic block copolymer

    OpenAIRE

    Erel, İrem; Karahan, H. Enis; Demirel, A. Levent; Tuncer, Cansel; Bütün, Vural

    2012-01-01

    We report the fabrication of hydrogen-bonded multilayers of micelles of a dually responsive, dicationic block copolymer, poly[2-(N-morpholino)ethyl methacrylate-block-2-(diisopropylamino)ethyl methacrylate] (PMEMA-b-PDPA). By taking advantage of the difference in the hydrophilicity of PMEMA and PDPA blocks, micelles with a PMEMA-corona and a PDPA-core were obtained above pH 6.5 and were assembled layer-by-layer at the surface with tannic acid (TA) at pH 7.4 through hydrogen bonding interactio...

  17. SANS study on the complex of cationic micelles and anionic polyelectrolytes

    International Nuclear Information System (INIS)

    We investigated the complex of cationic micelles and anionic polyelectrolytes. The cationic micelles have the composition of nonionic surfactant, Octa-ethyleneglycol mono n-tetradecyl ether (C14E8) and cationic surfactant, Tetradecyltrimethylammonium Bromide (TTAB), and the polyelectrolyte is Poly Styrene Sulfonic Acid, Sodium Salt (Mw.= 73900, PSS80k). By the charge interaction, they formed the complexes in the aqueous solution. This complex was studied by Small Angle Neutron Scattering (SANS). SANS study showed that the size distribution changed by the cationic surfactant-to-polyelectrolyte charge ratio. The structure of this complex was also studied

  18. Pluronic® P123/F127 mixed micelles delivering sorafenib and its combination with verteporfin in cancer cells

    Science.gov (United States)

    Pellosi, Diogo Silva; Moret, Francesca; Fraix, Aurore; Marino, Nino; Maiolino, Sara; Gaio, Elisa; Hioka, Noboru; Reddi, Elena; Sortino, Salvatore; Quaglia, Fabiana

    2016-01-01

    Here, we developed Pluronic® P123/F127 (poloxamer) mixed micelles for the intravenous delivery of the anticancer drug sorafenib (SRB) or its combination with verteporfin (VP), a photosensitizer for photodynamic therapy that should complement well the cytotoxicity profile of the chemotherapeutic. SRB loading inside the core of micelles was governed by the drug:poloxamer weight ratio, while in the case of the SRB–VP combination, a mutual interference between the two drugs occurred and only specific ratios could ensure maximum loading efficiency. Coentrapment of SRB did not alter the photophysical properties of VP, confirming that SRB did not participate in any bimolecular process with the photosensitizer. Fluorescence resonance energy-transfer measurement of micelles in serum protein-containing cell-culture medium demonstrated the excellent stability of the system in physiologically relevant conditions. These results were in line with the results of the release study showing a release rate of both drugs in the presence of proteins slower than in phosphate buffer. SRB release was sustained, while VP remained substantially entrapped in the micelle core. Cytotoxicity studies in MDA-MB231 cells revealed that at 24 hours, SRB-loaded micelles were more active than free SRB only at very low SRB concentrations, while at 24+24 hours a prolonged cytotoxic effect of SRB-loaded micelles was observed, very likely mediated by the block in the S phase of the cell cycle. The combination of SRB with VP under light exposure was less cytotoxic than both the free combination and VP-loaded micelles + SRB-loaded micelles combination. This behavior was clearly explainable in terms of micelle uptake and intracellular localization. Besides the clear advantage of delivering SRB in poloxamer micelles, our results provide a clear example that each photochemotherapeutic combination needs detailed investigations on their particular interaction, and no generalization on enhanced cytotoxic

  19. Polymer micelles with hydrophobic core and ionic amphiphilic corona. 1. Statistical distribution of charged and nonpolar units in corona.

    Science.gov (United States)

    Lysenko, Evgeny A; Kulebyakina, Alevtina I; Chelushkin, Pavel S; Rumyantsev, Artem M; Kramarenko, Elena Yu; Zezin, Alexander B

    2012-12-11

    Polymer micelles with hydrophobic polystyrene (PS) core and ionic amphiphilic corona from charged N-ethyl-4-vinylpyridinium bromide (EVP) and uncharged 4-vinylpyridine (4VP) units spontaneously self-assembled from PS-block-poly(4VP-stat-EVP) macromolecules in mixed dimethylformamide/methanol/water solvent. The fraction of statistically distributed EVP units in corona-forming block is β = [EVP]/([EVP]+[4VP]) = 0.3-1. Micelles were transferred into water via dialysis technique, and pH was adjusted to 9, where 4VP is insoluble. Structural characteristics of micelles were investigated both experimentally and theoretically as a function of corona composition β. Methods of dynamic and static light scattering, electrophoretic mobility measurements, sedimentation velocity, transmission electron microscopy, and UV spectrophotometry were applied. All micelles possessed spherical morphology. The aggregation number, structure, and electrophoretic mobility of micelles changed in a jumplike manner near β ~ 0.6-0.75. Below and above this region, micelle characteristics were constant or insignificantly changed upon β. Theoretical dependencies for micelle aggregation number, corona dimensions, and fraction of small counterions outside corona versus β were derived via minimization the micelle free energy, taking into account surface, volume, electrostatic, and elastic contributions of chain units and translational entropy of mobile counterions. Theoretical estimations also point onto a sharp structural transition at a certain corona composition. The abrupt reorganization of micelle structure at β ~ 0.6-0.75 entails dramatic changes in micelle dispersion stability in the presence of NaCl or in the presence of oppositely charged polymeric (sodium polymethacrylate) or amphiphilic (sodium dodecyl sulfate) complexing agents.

  20. Ascorbyl palmitate interaction with phospholipid monolayers: electrostatic and rheological preponderancy.

    Science.gov (United States)

    Mottola, Milagro; Wilke, Natalia; Benedini, Luciano; Oliveira, Rafael Gustavo; Fanani, Maria Laura

    2013-11-01

    Ascorbyl palmitate (ASC16) is an anionic amphiphilic molecule of pharmacological interest due to its antioxidant properties. We found that ASC16 strongly interacted with model membranes. ASC16 penetrated phospholipid monolayers, with a cutoff near the theoretical surface pressure limit. The presence of a lipid film at the interface favored ASC16 insertion compared with a bare air/water surface. The adsorption and penetration time curves showed a biphasic behavior: the first rapid peak evidenced a fast adsorption of charged ASC16 molecules to the interface that promoted a lowering of surface pH, thus partially neutralizing and compacting the film. The second rise represented an approach to the equilibrium between the ASC16 molecules in the subphase and the surface monolayer, whose kinetics depended on the ionization state of the film. Based on the Langmuir dimiristoylphosphatidylcholine+ASC16 monolayer data, we estimated an ASC16 partition coefficient to dimiristoylphosphatidylcholine monolayers of 1.5×10(5) and a ΔGp=-6.7kcal·mol(-1). The rheological properties of the host membrane were determinant for ASC16 penetration kinetics: a fluid membrane, as provided by cholesterol, disrupted the liquid-condensed ASC16-enriched domains and favored ASC16 penetration. Subphase pH conditions affected ASC16 aggregation in bulk: the smaller structures at acidic pHs showed a faster equilibrium with the surface film than large lamellar ones. Our results revealed that the ASC16 interaction with model membranes has a highly complex regulation. The polymorphism in the ASC16 bulk aggregation added complexity to the equilibrium between the surface and subphase form of ASC16, whose understanding may shed light on the pharmacological function of this drug. PMID:23806650

  1. Interaction of Puerarin with Phospholipid in Solid Dispersion

    Institute of Scientific and Technical Information of China (English)

    ZHAIGuang-xi; LOUHong-xiang; BIDian-zhou; ZOULi-jia

    2003-01-01

    Aim:To study the interaction of puerarin(PU) with phospholipid(PL)in solid dispersion.Methods:PU/PL solid dispersion was prepared with solvent evaporation and the interaction between PU and PL was studied by analysis of their ultraviolet spectra,infrared spectra,1H NMR spectra and thin layer chromatogram.Results:In chloroform the maximum absorption peak of pu in PU/PL mixture was located at 243nm,but 251nm for that of PU in solid dispersion.Howerver in methanol,QU in mixture or solid dispersion had the same maximum absorption peak location in ultraviolet spectra.Compared with the infrared spectra of mixture,that of solid dispersion showed the specific absorption peak location of berzene ring framework in PU molecule was markedly changed,the stretching vibration peak of P=O in PL molecule was shifted to high wavernumbers and the stretching vibration peak of C=C in PL molecule was disappeared.In 1H NMR spectra,most of the signals form PU in solid dispersion were weaken markedly or disappeared and the signals from the polar part of PL molecule were significantly changed.PU and PL in solid dispersion could be spearated on silica gel plate with the mixed solvent of chloroform,methanol and water (65:25:5)or ethyl acetate and methanol(10:1).Conclusion:In solid dispersion the benzene ring framework of PU molecule could act with the polar part and unsaturated part of PL molecule through charges transfer,and the interacted part could be surrounded by fat chains of PL molecule.

  2. Functional redundancy of CDP-ethanolamine and CDP-choline pathway enzymes in phospholipid biosynthesis: ethanolamine-dependent effects on steady-state membrane phospholipid composition in Saccharomyces cerevisiae.

    OpenAIRE

    McGee, T. P.; Skinner, H B; Bankaitis, V A

    1994-01-01

    It has been established that yeast membrane phospholipid content is responsive to the inositol and choline content of the growth medium. Alterations in the levels of transcription of phospholipid biosynthetic enzymes contribute significantly to this response. We now describe conditions under which ethanolamine can exert significant influence on yeast membrane phospholipid composition. We demonstrate that mutations which block a defined subset of the reactions required for the biosynthesis of ...

  3. Stable polymer micelle systems as anti-cancer drug delivery carriers

    Science.gov (United States)

    Zeng, Yi

    2005-07-01

    Several temporarily stable polymer micelle systems that might be used as ultrasonic-activated drug delivery carriers were synthesized and investigated. These polymeric micelle systems were PlurogelRTM, Tetronic RTM, poly(ethylene oxide)-b-poly(N-isopropylacrylamide) and poly(ethylene oxide)-b-poly(N-isopropylacrylamide-co-2-hydroxyethyl methacrylate-lactate n). In previous work in our lab, Pruitt et al. developed a stabilized drug carrier named PlurogelRTM [5, 6]. Unfortunately, the rate of the successful PlurogelRTM synthesis was only about 30% by simply following Pruitt's process. In this work, this rate was improved to 60% by combining the process of adding 0.15 M NaCl and/or 10 mul/ml n-butanol and by preheating the solution before polymerization. TetronicsRTM were proved not to be good candidates to form temporarily stable polymeric micelle system by polymerizing interpenetrating networks inside their micelle cores. Tetronic micelle systems treated by this process still were not stable at concentrations below their critical micelle concentration (CMC). Poly(ethylene oxide)-b-poly(N-isopropylacrylamide)-N,N-bis(acryloyl)cystamine micelle-like nanoparticles were developed and characterized. When the N,N-bis(acryloyl)cystamine (BAC) was from 0.2 wt% to 0.75 wt% of the mass of poly(N-isopropylacrylamide), diameters of the nanoparticles at 40°C were less than 150 nm. The cores of the nanoparticles were hydrophobic enough to sequester 1,6-diphenylhexatriene (DPH) and the anti-cancer drug doxorubicin (DOX). Nanoparticles with 0.5 wt% BAC stored at room temperature in 0.002 mg/ml solutions were stable for up to two weeks. Poly(ethylene oxide)-b-poly(N-isopropylacrylamide-co-2-hydroxyethyl methacrylate-lactate n) micelle systems were synthesized and characterized. The degree of polymerization of lactate side group, n, was 3 or 5. The copolymers with N-isopropylacrylamide:2-hydroxyethyl methacrylate-lactate3: poly(ethylene oxide) (NIPAAm:HEMA-lactate 3:PEO) ratios of

  4. Neural modeling of bromelain extraction by reversed micelles

    Directory of Open Access Journals (Sweden)

    Ana Maria Frattini Fileti

    2010-04-01

    Full Text Available A pulsed-cap microcolumn was used for bromelain extraction from pineapple juice by reversed micelles. The cationic micellar solution used BDBAC as the surfactant, isooctane as the solvent and hexanol as the co-solvent. In order to capture the dynamic behavior and the nonlinearities of the column, the operating conditions were modified in accordance with the central composite design for the experiment, using the ratio between the light phase flow rate and the total flow rate, and the time interval between pulses. The effects on the purification factor and on total protein yield were modeled via neural networks. The best topology was defined as 16-9-2, and the input layer was a moving window of the independent variables. The neural model successfully predicted both the purification factor and the total protein yield from historical data. At the optimal operating point, a purification factor of 4.96 and a productivity of 1.29 mL/min were obtained.Uma micro-coluna com campânulas pulsantes foi utilizada para a extração de bromelina a partir de suco de abacaxi, usando micelas reversas. A solução catiônica micelar foi composta do surfactante BDBAC, do solvente iso-octano e do co-solvente hexanol. Seguindo um planejamento experimental, perturbações foram impostas à coluna de extração com o objetivo de capturar seu comportamento dinâmico e suas não-linearidades, usando a razão entre a vazão da fase leve e vazão total, e o intervalo de tempo entre os pulsos. Os efeitos das variáveis independentes sobre o fator de purificação e sobre o rendimento em proteínas totais foram modelados via redes neurais artificiais. A melhor topologia de rede obtida foi definida como 16-9-2, usando um esquema de janela móvel no tempo das variáveis independentes. O modelo neural obtido do histórico do processo se mostrou adequado para predizer simultaneamente o fator de purificação e o rendimento do processo em proteínas totais. No ponto ótimo de

  5. Batch and continuous extraction of bromelain enzyme by reversed micelles

    Directory of Open Access Journals (Sweden)

    Ana Maria Frattini Fileti

    2009-10-01

    Full Text Available The main aim of this study was to optimize the conditions for bromelain extraction by reversed micelles from pineapple juice (Ananas comosus. The purification was carried out in batch extraction and a micro-column with pulsed caps for continuous extraction. The cationic micellar solution was made of BDBAC as a surfactant, isooctane as a solvent and hexanol as a co-solvent. For the batch process, a purification factor of 3 times at the best values of surfactant agent, co-solvent and salt concentrations, pH of the back and forward extractions were, 100 mM, 10% v/v, 1 M, 3.5 and 8, respectively. For the continuous operation, independent variables optimal point was determined: ratio between light phase flow rate and total flow rate equal to 0.67 and 1 second for the time interval between the pulses. This optimal point led to a productivity of 1.29 mL/min and a purification factor of 4.96.Este trabalho teve como objetivo principal otimizar as condições para extração da bromelina do suco do abacaxi (Ananas comosus por micelas reversas. A purificação foi feita usando o processo de extração em batelada e contínuo, este último em uma micro-coluna de campânulas pulsantes. A solução micelar catiônica foi preparada com o surfactante BDBAC, i-octano como solvente e hexanol como co-solvente. Na extração em batelada encontrou-se um fator de purificação de 3 vezes, e seus melhores valores de concentração do agente surfactante, co-solvente e sal, de pH da re-extração e extração, foram respectivamente iguais a: 100 mM, 10% v/v, 1 M, 3,5 e 8. Para a operação contínua, as variáveis independentes ótimas foram: 0,67 para a razão entre as taxas de fluxos da fase leve e a total e 1 s para o intervalo de tempo entre pulsos das campânulas. Este ponto ótimo leva a uma produtividade de 1,29 mL/min e a um fator de purificação igual a 4,96.

  6. Correlating phospholipid fatty acids (PLFA) in a landfill leachate polluted aquifer with biogeochemical factors by multivariate statistical methods

    DEFF Research Database (Denmark)

    Ludvigsen, Liselotte; Albrechtsen, Hans-Jørgen; Rootzén, Helle;

    1997-01-01

    effect and to redox processes and the second principal component described the geological and geochemical features of the samples. Dependent on the data transformation of the phospholipid fatty acid profiles in either absolute concentrations (logarithm transformed) or in mol% of total phospholipid fatty...... acids, different groups of samples and outliers were revealed by the principal component analysis. The principal component analysis on data in absolute concentrations revealed that many phospholipid fatty acids reflected the pollution effect on the biomass composition. In contrast, the phospholipid...... fatty acids in mol% divided the samples into one group of the more polluted samples and another with the nearly unpolluted samples. The important phospholipid fatty acids for this grouping were mainly a few of the normal saturated phospholipid fatty acids (10:0, 16:0 and 18:0). Discriminant analysis...

  7. The influence of blood on the efficacy of intraperitoneally applied phospholipids for prevention of adhesions

    Directory of Open Access Journals (Sweden)

    Oettinger Alexander P

    2007-07-01

    Full Text Available Abstract Background The formation of adhesions following abdominal surgery is a well known problem. In previous studies we demonstrated the efficacy and safety of intraperitoneally applied phospholipids in order to prevent adhesion formation. This study evaluates the influence of blood on the efficacy of intraperitoneally applied phospholipids for prevention of adhesions. Methods In 40 Chinchilla rabbits adhesions were induced by median laparotomy, standardized abrasion of the visceral and parietal peritoneum in defined areas of the ventral abdominal wall and the caecum. The animals were randomly divided into four groups. They received either phospholipids 3.0% or normal saline (NaCl 0,9% (5 ml/kg body weight. In 50% of the rabbits we simulated intraperitoneal bleeding by administration of blood (1,5 ml/kg body weight. The other half served as control group. Ten days following the operation the animals were sacrificed and adhesion formation was assessed by computer aided planimetry and histopathologic examination. Results The median adhesion surface area in the NaCl-group (n = 9 amounted to 68,72 mm2, in the NaCl+Blood-group (n = 10 147,68 mm2. In the Phospholipid (PhL-group (n = 9 the median adhesion surface area measured 9,35 mm2, in the PhL+Blood-group (n = 9 11,95 mm2. The phospholipid groups had a significantly smaller adhesion surface area (p Conclusion Again these results confirm the efficacy of phospholipids in the prevention of adhesions in comparison to NaCl (p = 0,04. We also demonstrated the adhesion preventing effect of phospholipids in the presence of intraperitoneal blood.

  8. Some effects of sulphuric dioxide and irradiation on lung surfactant system phospholipids

    International Nuclear Information System (INIS)

    The pulmonary surfactant phospholipid alterations following the combined treatment with sulphuric dioxide and gamma radiation have been examined. Male Wistar rats have been exposed for eight days (five hours daily) to 70 mg/m-3 sulphuric dioxide inhalation, followed by a single dose of 4 Gy (Δ1=1,8 mm, 1 mm Cu filter 220 kV). Samples have been taken of bronchoalveolar lavage fluid (BAL) and lung tissue homogenates (LT) on days 1, 15 and 30 after the X-ray exposure. The total phospholipids, cholesterol and protein are measured. Phospholipids were separated by one-phase one-dimensional thin-layer chromatography using silica gel precoated plates. For the phospholipids an increase of 30-40 % in BAL on days 1 and 15 post-treatment has been observed. The cholesterol indicates a considerable elevation on day 15 markedly pronounced upon combined treatment. For the lung tissue the results are controversial: phospholipids markedly decrease mainly due to their enhanced exocytosis into the alveolar spaces (BAL), but the cholesterol is increased on day 15 after the X-ray irradiation. Nevertheless that the relative contribution of the whole cell free homogenate is almost unaltered, an augmentation in the phosphatidylcholine and phosphatydylglycerol has been found. The phosphatidylcholine content in BAL has been augmented until day 15 post-treatment, whereas the phosphatidylglycerol content has been the highest on the first day and mostly pronounced after combined SO2-inhalation and irradiation. In the lung tissue a simultaneous decrease of the phospholipids has been noticed. The results show that deleterious agents not only affect the upper respiratory airways, but the lung parenchima and the type 2 pneumocytes that synthesize and secrete the pulmonary surfactant complex as well. The values of the phospholipids, both in BAL and lung tissue, close to those of the controls in later period (30 days), have been viewed as intensified restorative processes in type 2 pneumocytes

  9. Synthesis of sn-1 functionalized phospholipids as substrates for secretory phospholipase A2

    DEFF Research Database (Denmark)

    Linderoth, Lars; Peters, Günther H.J.; Jørgensen, K.;

    2007-01-01

    of the allyl-substituents by a zinc mediated allylation. Small unilamellar liposomes composed of phospholipids 1 and 2 were subjected to sPLA2 activity measurements. Our results show that only phospholipid 1 is hydrolyzed by the enzyme. Molecular dynamics simulations revealed that the lack of hydrolysis...... of phospholipid 2 is due to steric hindrance caused by the bulky side chain of the substrate allowing only limited access of water molecules to the active site....

  10. Phospholipid Synthesis by Staphylococcus aureus during (Sub)Lethal Attack by Mammalian 14-Kilodalton Group IIA Phospholipase A2

    OpenAIRE

    Foreman-Wykert, Amy K.; Weiss, Jerrold; Elsbach, Peter

    2000-01-01

    Killing of gram-positive bacteria by mammalian group IIA phospholipases A2 (PLA2) requires the catalytic activity of the enzyme. However, nearly complete degradation of the phospholipids can occur with little effect on bacterial viability, suggesting that PLA2-treated bacteria can biosynthetically replace phospholipids that are lost due to PLA2 action. In the presence of albumin, phospholipid degradation products are quantitatively sequestered extracellularly. In the absence of albumin, the b...

  11. Recent advances and future prospects of phyto-phospholipid complexation technique for improving pharmacokinetic profile of plant actives.

    Science.gov (United States)

    Khan, Junaid; Alexander, Amit; Ajazuddin; Saraf, Swarnlata; Saraf, Shailendra

    2013-05-28

    The phyto-phospholipid complexation technique has emerged as one of the leading methods of improving bioavailability of phytopharmaceuticals having poor competency of solubilizing and crossing the biological membranes. Several plant actives in spite having potent in vitro pharmacological activities have failed to demonstrate similar in vivo response. Such plant actives have been made more effective systemically by incorporating them with dietary phospholipids forming new cellular structures which are amphipathic in nature. In the last few years phospholipids have been extensively explored for improved bioavailability and efficacy of plant drugs. Further, it is also much relevant to mention that phospholipids show unique compatibility with biological membranes and have inherent hepatoprotective activity. Different methods have been adopted to formulate phospholipid complexes of plant extractives utilizing varying solvent systems, molar ratios of drug/phospholipids and different drying techniques. Some methods of formulating such drug-phospholipid complexes have been patented as well. However, the stability of phyto-phospholipid complexes is still a matter of concern which needs attention. But still a number of products exploiting this technique are under clinical trials and some of them are now in market. The current review highlights key findings of recent years with our own viewpoints which can give the new directions to this strategy and also includes advancements in the technical aspects of phyto-phospholipid formulations which have been done in the recent past with future challenges. PMID:23474031

  12. Ramping of pH Across the Water-Pool of a Reverse Micelle.

    Science.gov (United States)

    Mukherjee, Puspal; Gupta, Shradhey; Rafiq, Shahnawaz; Yadav, Rajeev; Jain, Vipin Kumar; Raval, Jayraj; Sen, Pratik

    2016-02-23

    In this work, we have addressed the problem of "acidity" of the water-pool of a reverse micelle (RM) through the well-known inversion of sucrose reaction as a tool of investigation. This reaction has been performed inside positively and negatively charged RM and the rates are compared with that in bulk water. We propose that the buffer-like action in a water-pool is much stronger than expected earlier. The rate of sucrose hydrolysis slowed down in the negatively charged AOT reverse micelle while it sped up for the positively charged CTAB reverse micelle. However, temperature-dependent measurements showed that the activation energy remained the same for all the cases. It has been concluded that a proton gradient exists inside the water-pool of the reverse micelle and it determines the buffer-like action of the water-pool that persists until about 2 N of HCl in AOT RM of w(0) = 10.5.

  13. Oscillatory structural forces due to nonionic surfactant micelles: data by colloidal-probe AFM vs theory.

    Science.gov (United States)

    Christov, Nikolay C; Danov, Krassimir D; Zeng, Yan; Kralchevsky, Peter A; von Klitzing, Regine

    2010-01-19

    Micellar solutions of nonionic surfactants Brij 35 and Tween 20 are confined between two surfaces in a colloidal-probe atomic-force microscope (CP-AFM). The experimentally detected oscillatory forces due to the layer-by-layer expulsion of the micelles agree very well with the theoretical predictions for hard-sphere fluids. While the experiment gives parts of the stable branches of the force curve, the theoretical model allows reconstruction of the full oscillatory curve. Therewith, the strength and range of the ordering could be determined. The resulting aggregation number from the fits of the force curves for Brij 35 is close to 70 and exhibits a slight tendency to increase with the surfactant concentration. The last layer of micelles cannot be pressed out. The measured force-vs-distance curve has nonequilibrium portions, which represent "jumps" from one to another branch of the respective equilibrium oscillatory curve. In the case of Brij 35, at concentrations force oscillations are almost suppressed, which implies that the micelles of this surfactant are labile and are demolished by the hydrodynamic shear stresses due to the colloidal-probe motion. The comparison of the results for the two surfactants demonstrates that in some cases the micelles can be destroyed by the CP-AFM, but in other cases they can be stable and behave as rigid particles. This behavior correlates with the characteristic times of the slow micellar relaxation process for these surfactants. PMID:20067306

  14. Deactivation kinetics of yeast alcohol dehydrogenase in aerosol OT/isooctane reverse micelles

    Energy Technology Data Exchange (ETDEWEB)

    Chen, D.; Chen, H.; Huang, T. [National Cheng Kung University, Tainan (Taiwan, Province of China)

    1995-10-10

    The deactivation kinetics of yeast alcohol dehydrogenase (YADH) in both aerosol OT/isooctane reverse micelles and aqueous buffer were studied. The YADH entrapped in reverse micelles could retain activity for above 24 hr although it was less stable than dissolved in aqueous buffer. Both the activity-time curves for the YADH in reverse micelles and in aqueous buffer exhibited a rather rapid exponential decay within the early 2 hr, followed by a slower exponential decay during the remaining period. A series-type enzyme deactivation model involving two first-order steps and one active intermediate was used to describe the deactivation behavior of YADH. The kinetic parameters of the deactivation rate equations were obtained by optimization method. In aqueous buffer, the deactivation rate of YADH exhibited a maximum around a Tris concentration of 0.1 mol{center_dot}m{sup -3}. The deactivation rate of YADH in reverse micelles was strongly dependent on Tris concentration and the molar ratio of water to surfactant ({omega}0). The residual activity percentage of the active intermediate increased with the increase of {omega}0 and Tris concentration, while both the rate constants for the first and second first-order deactivation steps decreased with the increase of Tris concentration. 30 refs., 2 figs., 2 tabs.

  15. Selective Affinity Separation of Yeast Alcohol Dehydrogenase by Reverse Micelles with Unbound Triazine Dye*

    Institute of Scientific and Technical Information of China (English)

    张天喜; 刘会洲; 陈家镛

    2001-01-01

    The reversed micelles were formed with cationic cetyltrimethylammonium bromide (CTAB) as surfactant and n-hexanol as cosolvent in the CTAB (50 mmol·L- 1)/hexanol (15% by volume)/hexane system. Cibacron Blue 3GA (CB) as an affinity ligand in the aqueous phase was directly introduced to the reversed micelles with electrostatic interaction between anionic CB and cationic surfactant. High molecular weight (Mr) protein, yeast alcohol dehydrogenase (YADH, Mr = 141000) from baker's yeast, has been purified using the affinity reversed micelles by the phase transfer method. Various parameters, such as CB concentration, pH and ionic strength, on YADH forward and backward transfer were studied. YADH can be transferred into and out from the reversed micelles under mild conditions (only by regulation of solution pH and salt concentration) with the successful recoveryof most YADH activity. Both forward and backward extractions occurred when the aqueous phase pH>pI with electrostatic attraction between YADH and CTAB. The recovery of YADH activity and purification factor have been improved with addition of a small amount of affinity CB. The recovery of YADH activity obtained was 99% and the purification factor was about 4.0-fold after one cycle of full forward and backward extraction. The low ionic strength in the initial aqueous phase might be responsible for the YADH transfer into the reversed micellar phase.

  16. Porphyrins in Reverse Micelles:the Side-chain Length and the Triplet-state Lifetime

    Institute of Scientific and Technical Information of China (English)

    Jun Hua YU; Yu Xiang WENG; Xue Song WANG; Lei ZHANG; Bao Wen ZHANG; Yi CAO

    2003-01-01

    Using bis(2-ethylhexyl) sodium sulfosuccinate (AOT) as surfactant, two amphiphilic porphyrin terminated with imidazole were studied in AOT/iso-octane/water reverse micelles, intending to mimic the relationship between microenvironments in organism and the amphiphilic properties of porphyrins for photodynamic therapy drugs.

  17. Photoinduced formation of threadlike micelles from mixtures of a cationic surfactant and a stilbene amphiphile.

    Science.gov (United States)

    Takahashi, Yutaka; Kishimoto, Mai; Kondo, Yukishige

    2016-05-15

    This study examined the influence of ultraviolet (UV) irradiation on aqueous surfactant solutions containing an anionic stilbene derivative (sodium [4-[(E)-2-(4-butylphenyl)ethenyl]phenoxy]acetate; C4StilNa) as a photoresponsive skeleton. Prior to UV irradiation, an aqueous solution of cetyltrimethylammonium bromide (CTAB) and C4StilNa was a low-viscosity fluid forming spheroidal micelles. Exposure of the low-viscosity fluid to UV light resulted in the formation of threadlike micelles and an increase in the viscosity of the aqueous CTAB/C4StilNa solution. (1)H nuclear magnetic resonance spectroscopy indicated that the photochemically induced isomerization and dimerization reactions of C4StilNa molecules had occurred in the aggregates due to UV irradiation. Overall, the structural transformation of the stilbene groups in the C4StilNa molecules with the photochemical reactions leads to an increase in the critical packing parameter and consequently a photoinduced transition of spheroidal micelles to threadlike micelles. PMID:26967168

  18. Unimolecular micelles of amphiphilic cyclodextrin-core star-like block copolymers for anticancer drug delivery.

    Science.gov (United States)

    Xu, Zhigang; Liu, Shiying; Liu, Hui; Yang, Cangjie; Kang, Yuejun; Wang, Mingfeng

    2015-11-11

    Well-defined star-like amphiphilic polymers composed of a β-cyclodextrin core, from which 21 hydrophobic poly(lactic acid) arms and hydrophilic poly(ethylene glycol) arms are grafted sequentially, form robust and uniform unimolecular micelles that are biocompatible and efficient in the delivery of anticancer drugs. PMID:26121632

  19. Peptide micelle-mediated curcumin delivery for protection of islet β-cells under hypoxia.

    Science.gov (United States)

    Han, Jaesik; Oh, Jungju; Ihm, Sung-Hee; Lee, Minhyung

    2016-08-01

    Islet transplantation is one of many therapeutic approaches for the treatment of diabetes. During transplant procedures, the isolated islets are subjected to hypoxic conditions, and undergo the apoptotic process. Curcumin has a cytoprotective effect, and may therefore be useful for the protection of islets under hypoxia. However, curcumin is hydrophobic, and an efficient curcumin carrier is required for effective treatment. In this study, R3V6 peptide micelles, composed of a 3-arginine stretch and 6-valine stretch, were evaluated as a curcumin carrier to INS-1 insulinoma cells. Curcumin was loaded into R3V6 micelles at a weight ratio of 10:3 (R3V6:curcumin). The size and surface charge of the curcumin-loaded R3V6 micelles (R3V6-curcumin) were approximately 250 nm and 17.49 mV, respectively. R3V6-curcumin delivered curcumin to the INS-1 cells more efficiently than either curcumin alone or a simple mixture of R3V6 and curcumin. MTT assay indicated that under hypoxia, R3V6-curcumin protected INS-1 cells more efficiently than curcumin alone. TUNEL and reactive oxygen species (ROS) assays suggested that R3V6-curcumin reduced INS-1 cell apoptosis under hypoxia. These results demonstrate that R3V6 peptide micelles are an effective carrier of curcumin, and that R3V6-curcumin may improve the viability of pancreatic β-cells in islet transplantation. PMID:26768151

  20. Inulin based micelles loaded with curcumin or celecoxib with effective anti-angiogenic activity.

    Science.gov (United States)

    Mandracchia, Delia; Tripodo, Giuseppe; Trapani, Adriana; Ruggieri, Simona; Annese, Tiziana; Chlapanidas, Theodora; Trapani, Giuseppe; Ribatti, Domenico

    2016-10-10

    Curcumin (CUR) and celecoxib (CLX) are two highly hydrophobic drugs which show bioavailability problems due to their poor aqueous solubility. The aim of this study was to encapsulate each of these drugs in micelles based on biodegradable and amphiphilic polymers to investigate their anti-angiogenesis activity. Here we use an amphiphilic polymer, based on two natural substances from renewable resources (Inulin and Vitamin E, INVITE), as a self-assembling system for the drug delivery of CUR and CLX. By the in vivo assay of chick embryo chorioallantoic membrane (CAM) it was assessed that both INVITE-CUR and INVITE-CLX micelles possess remarkable anti-angiogenic activity, while the INVITE micelles alone resulted intrinsically pro-angiogenic. Furthermore, it has been shown that encapsulation of CUR and CLX in INVITE micelles enhances of several magnitudes the water-solubility of CUR and CLX (14·10(5) and 3·10(2) times for CUR and CLX, respectively). These results may have interesting implications not only in anticancer or diabetic maculopathy therapy based on the anti-angiogenesis strategy but also for regenerative medicine where over-production of new vessels is required.