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Sample records for zwitterionic dodecylphosphocholine micelle

  1. 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...... in the micellar core and the polar side chains protruding into the aqueous phase. There is overwhelming evidence that points to the significant and indispensable participation of hydrophobic residues in binding to the zwitterionic interface. The simulation starts with a conformation that is unbiased toward...

  2. Interactions of myelin basic protein with mixed dodecylphosphocholine/palmitoyllysophosphatidic acid micelles

    International Nuclear Information System (INIS)

    Mendz, G.L.; Brown, L.R.; Martenson, R.E.

    1990-01-01

    The interactions of myelin basic protein and peptides derived from it with detergent micelles of lysophosphatidylglycerol, lysophosphatidylserine, palmitoyllysophosphatidic acid, and sodium lauryl sulfate, and with mixed micelles of the neutral detergent dodecylphosphocholine and the negatively charged detergent palmitoyllysophosphatidic acid, were investigated by 1 H NMR spectroscopy and circular dichroic spectropolarimetry. The results with single detergents suggested that there are discrete interaction sites in the protein molecule for neutral and anionic detergent micelles and that at least some of these sites are different for each type of detergent. The data on the binding of the protein and peptides to mixed detergent micelles suggested that intramolecular interactions in the intact protein and in one of the longer peptides limited the formation of helices and also that a balance between hydrophobic and ionic forces is achieved in the interactions of the peptides with the detergents. At high detergent/protein molar ratios, hydrophobic interactions appeared to be favored

  3. Structural Study of a New HIV-1 Entry Inhibitor and Interaction with the HIV-1 Fusion Peptide in Dodecylphosphocholine Micelles.

    Science.gov (United States)

    Pérez, Yolanda; Gómara, Maria José; Yuste, Eloísa; Gómez-Gutierrez, Patricia; Pérez, Juan Jesús; Haro, Isabel

    2017-08-25

    Previous studies support the hypothesis that the envelope GB virus C (GBV-C) E1 protein interferes the HIV-1 entry and that a peptide, derived from the region 139-156 of this protein, has been defined as a novel HIV-1 entry inhibitor. In this work, we firstly focus on the characterization of the structural features of this peptide, which are determinant for its anti-HIV-1 activity and secondly, on the study of its interaction with the proposed viral target (i.e., the HIV-1 fusion peptide). We report the structure of the peptide determined by NMR spectroscopy in dodecylphosphocholine (DPC) micelles solved by using restrained molecular dynamics calculations. The acquisition of different NMR experiments in DPC micelles (i.e., peptide-peptide titration, diffusion NMR spectroscopy, and addition of paramagnetic relaxation agents) allows a proposal of an inhibition mechanism. We conclude that a 18-mer peptide from the non-pathogenic E1 GBV-C protein, with a helix-turn-helix structure inhibits HIV-1 by binding to the HIV-1 fusion peptide at the membrane level, thereby interfering with those domains in the HIV-1, which are critical for stabilizing the six-helix bundle formation in a membranous environment. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Dodecylphosphocholine Micelles Induce Amyloid Formation of the PrP(110-136 Peptide via an α-Helical Metastable Conformation.

    Directory of Open Access Journals (Sweden)

    Simon Sauvé

    Full Text Available A peptide encompassing the conserved hydrophobic region and the first β-strand of the prion protein (PrP(110-136 shown to interact with the surface of dodecylphosphocholine micelles adopts an α-helical conformation that is localized below the head-group layer. This surface-bound peptide has a half-life of one day, and readily initiates the formation of amyloid fibrils. The presence of the latter was confirmed using birefringence microscopy upon Congo red binding and thioflavin T-binding induced fluorescence. The observation of this metastable α-helical conformer provides a unique snapshot of the early steps of the inter-conversion pathway. These findings together with the body of evidence from the prion literature allowed us to propose a mechanism for the conversion of PrPC to amyloid material.

  5. Two-dimensional 1H NMR experiments show that the 23-residue magain in antibiotic peptide is an α-helix in dodecylphosphocholine micelles, sodium dodecylsulfate micelles, and trifluoroethanol/water solution

    International Nuclear Information System (INIS)

    Gesell, Jennifer; Zasloff, Michael; Opella, Stanley J.

    1997-01-01

    Magainin2 is a 23-residue antibiotic peptide that disrupts the ionic gradient across certain cell membranes. Two-dimensional 1H NMR spectroscopy was used to investigate the structure of the peptide in three of the membrane environments most commonly employed in biophysical studies. Sequence-specific resonance assignments were determined for the peptide in perdeuterated dodecylphosphocholine (DPC) and sodium dodecylsulfate micelles and confirmed for the peptide in 2,2,2-trifluoroethanol solution. The secondary structure is shown to be helical in all of the solvent systems. The NMR data were used as a set of restraints for a simulated annealing protocol that generated a family of three-dimensional structures of the peptide in DPC micelles, which superimposed best between residues 4 and 20. For these residues, the mean pairwise rms difference for the backbone atoms is 0.47 ± 0.10A from the average structure. The calculated peptide structures appear to be curved,with the bend centered at residues Phe12 and Gly13

  6. Polymeric microcapsules assembled from a cationic/zwitterionic pair of responsive block copolymer micelles.

    Science.gov (United States)

    Addison, Timothy; Cayre, Olivier J; Biggs, Simon; Armes, Steven P; York, David

    2010-05-04

    Using a layer-by-layer (LbL) approach, this work presents the preparation of hollow microcapsules with a membrane constructed entirely from a cationic/zwitterionic pair of pH-responsive block copolymer micelles. Our previous work with such systems highlighted that, in order to retain the responsive nature of the individual micelles contained within the multilayer membranes, it is important to optimize the conditions required for the selective dissolution of the sacrificial particulate templates. Consequently, here, calcium carbonate particles have been employed as colloidal templates as they can be easily dissolved in aqueous environments with the addition of chelating agents such as ethylenediaminetetraacetic acid (EDTA). Furthermore, the dissolution can be carried out in solutions buffered to a desirable pH so not to adversely affect the pH sensitive micelles forming the capsule membranes. First, we have deposited alternating layers of anionic poly[2-(dimethylamino)ethyl methacrylate-block-poly(2-(diethylamino)ethyl methacrylate)] (PDMA-PDEA) and cationic poly(2-(diethylamino)ethyl)methacrylate-block-poly(methacrylic acid) (PDEA-PMAA) copolymer micelles onto calcium carbonate colloidal templates. After deposition of five micelle bilayers, addition of dilute EDTA solution resulted in dissolution of the calcium carbonate and formation of hollow polymer capsules. The capsules were imaged using atomic force microscopy (AFM) and scanning electron microscopy (SEM), which shows that the micelle/micelle membrane is sufficiently robust to withstand dissolution of the supporting template. Quartz crystal microbalance studies were conducted and provide good evidence that the micelle multilayer structure is retained after EDTA treatment. In addition, a hydrophobic dye was incorporated into the micelle cores prior to adsorption. After dissolution of the particle template, the resulting hollow capsules retained a high concentration of dye, suggesting that the core

  7. Specific Binding of Adamantane Drugs and Direction of their Polar Amines in the Pore of the Influenza M2 Transmembrane Domain in Lipid Bilayers and Dodecylphosphocholine Micelles Determined by NMR Spectroscopy

    Science.gov (United States)

    Cady, Sarah D.; Wang, Jun; Wu, Yibing; DeGrado, William F.; Hong, Mei

    2011-01-01

    The transmembrane domain of the influenza M2 protein (M2TM) forms a tetrameric proton channel important for the virus lifecycle. The proton-channel activity is inhibited by amine-containing adamantyl drugs amantadine and rimantadine, which have been shown to bind specifically to the pore of M2TM near Ser31. However, whether the polar amine points to the N- or C-terminus of the channel has not yet been determined. Elucidating the polar group direction will shed light on the mechanism by which drug binding inhibits this proton channel and will facilitate rational design of new inhibitors. In this study, we determine the polar amine direction using M2TM reconstituted in lipid bilayers as well as DPC micelles. 13C-2H rotational-echo double-resonance NMR experiments of 13C-labeled M2TM and methyl-deuterated rimantadine in lipid bilayers showed that the polar amine pointed to the C-terminus of the channel, with the methyl group close to Gly34. Solution NMR experiments of M2TM in dodecylphosphocholine (DPC) micelles indicate that drug binding causes significant chemical shift perturbations of the protein that are very similar to those seen for M2TM and M2(18–60) bound to lipid bilayers. Specific 2H-labeling of the drugs permitted the assignment of drug-protein cross peaks, which indicate that amantadine and rimantadine bind to the pore in the same fashion as for bilayer-bound M2TM. These results strongly suggest that adamantyl inhibition of M2TM is achieved not only by direct physical occlusion of the pore but also by perturbing the equilibrium constant of the proton-sensing residue His37. The reproduction of the pharmacologically relevant specific pore-binding site in DPC micelles, which was not observed with a different detergent, DHPC, underscores the significant influence of the detergent environment on the functional structure of membrane proteins. PMID:21381693

  8. Synthesis of mesoporous nano-hydroxyapatite by using zwitterions surfactant

    Science.gov (United States)

    Mesoporous nano-hydroxyapatite (mn-HAP) was successfully synthesized via a novel micelle-templating method using lauryl dimethylaminoacetic acid as zwitterionic surfactant. The systematic use of such a surfactant in combination with microwave energy inputenables the precise contr...

  9. Molecular dynamics investigation of the influence of anionic and zwitterionic interfaces on antimicrobial peptides' structure: implications for peptide toxicity and activity

    DEFF Research Database (Denmark)

    Khandelia, Himanshu; Kaznessis, Yiannis N

    2006-01-01

    Molecular dynamics simulations of three related helical antimicrobial peptides have been carried out in zwitterionic diphosphocholine (DPC) micelles and anionic sodiumdodecylsulfate (SDS) micelles. These systems can be considered as model mammalian and bacterial membrane interfaces, respectively...

  10. How can a beta-sheet peptide be both a potent antimicrobial and harmfully toxic? Molecular dynamics simulations of protegrin-1 in micelles

    DEFF Research Database (Denmark)

    Langham, Allison A; Khandelia, Himanshu; Kaznessis, Yiannis N

    2006-01-01

    In this work, the naturally occurring beta-hairpin antimicrobial peptide protegrin-1 (PG-1) is studied by molecular dynamics simulation in all-atom sodium dodecylsulfate and dodecylphosphocholine micelles. These simulations provide a high-resolution picture of the interactions between the peptide...

  11. Critical micelle concentration values for different surfactants measured with solid-phase microextraction fibers

    NARCIS (Netherlands)

    Haftka, Joris J H; Scherpenisse, Peter; Oetter, G??nter; Hodges, Geoff; Eadsforth, Charles V.; Kotthoff, Matthias; Hermens, Joop L M

    The amphiphilic nature of surfactants drives the formation of micelles at the critical micelle concentration (CMC). Solid-phase microextraction (SPME) fibres were used in the present study to measure CMC values of twelve nonionic, anionic, cationic and zwitterionic surfactants. The SPME derived CMC

  12. Conjugated polymer zwitterions and solar cells comprising conjugated polymer zwitterions

    Science.gov (United States)

    Emrick, Todd; Russell, Thomas; Page, Zachariah; Liu, Yao

    2018-06-05

    A conjugated polymer zwitterion includes repeating units having structure (I), (II), or a combination thereof ##STR00001## wherein Ar is independently at each occurrence a divalent substituted or unsubstituted C3-30 arylene or heteroarylene group; L is independently at each occurrence a divalent C1-16 alkylene group, C6-30arylene or heteroarylene group, or alkylene oxide group; and R1 is independently at each occurrence a zwitterion. A polymer solar cell including the conjugated polymer zwitterion is also disclosed.

  13. Effect of micelle interface on the binding of anticoccidial PW2 peptide

    International Nuclear Information System (INIS)

    Tinoco, Luzineide W.; Gomes-Neto, Francisco; Valente, Ana Paula; Almeida, Fabio C. L.

    2007-01-01

    PW2 is an anticoccidial peptide active against Eimeria acervulina and Eimeria tenella. We determined the structure of PW2 in dodecylphosphocholine micelles. The structure showed two distinct regions: an amphipathic N-terminal 3 10 helix and an aromatic region containing WWR interface-binding motif. The aromatic region acted as a scaffold of the protein in the interface and shared the same structure in both DPC and SDS micelles. N-terminal helix interacted with DPC but not with SDS interface. Chemical shift change was slow when SDS was added to PW2 in DPC and fast when DPC was added to PW2 in SDS, indicating that interaction with DPC micelles was kinetically more stable than with SDS micelles. Also, DPC interface was able to accommodate PW2, but it maintained the conformational arrangement in the aromatic region observed for SDS micelles. This behavior, which is different from that observed for other antimicrobial peptides with WWR motif, may be associated with the absence of PW2 antibacterial activity and its selectivity for Eimeria parasites

  14. Effect of micelle interface on the binding of anticoccidial PW2 peptide

    Energy Technology Data Exchange (ETDEWEB)

    Tinoco, Luzineide W. [Universidade Federal do Rio de Janeiro, Nucleo de Pesquisas de Produtos Naturais (Brazil); Gomes-Neto, Francisco; Valente, Ana Paula; Almeida, Fabio C. L. [Universidade Federal do Rio de Janeiro, Centro Nacional de Ressonancia Magnetica Nuclear Jiri Jonas, Instituto de Bioquimica Medica, Programa de Biologia Estrutural (Brazil)], E-mail: falmeida@cnrmn.bioqmed.ufrj.br

    2007-12-15

    PW2 is an anticoccidial peptide active against Eimeria acervulina and Eimeria tenella. We determined the structure of PW2 in dodecylphosphocholine micelles. The structure showed two distinct regions: an amphipathic N-terminal 3{sub 10} helix and an aromatic region containing WWR interface-binding motif. The aromatic region acted as a scaffold of the protein in the interface and shared the same structure in both DPC and SDS micelles. N-terminal helix interacted with DPC but not with SDS interface. Chemical shift change was slow when SDS was added to PW2 in DPC and fast when DPC was added to PW2 in SDS, indicating that interaction with DPC micelles was kinetically more stable than with SDS micelles. Also, DPC interface was able to accommodate PW2, but it maintained the conformational arrangement in the aromatic region observed for SDS micelles. This behavior, which is different from that observed for other antimicrobial peptides with WWR motif, may be associated with the absence of PW2 antibacterial activity and its selectivity for Eimeria parasites.

  15. Zwitterionic materials for antifouling membrane surface construction.

    Science.gov (United States)

    He, Mingrui; Gao, Kang; Zhou, Linjie; Jiao, Zhiwei; Wu, Mengyuan; Cao, Jialin; You, Xinda; Cai, Ziyi; Su, Yanlei; Jiang, Zhongyi

    2016-08-01

    Membrane separation processes are often perplexed by severe and ubiquitous membrane fouling. Zwitterionic materials, keeping electric neutrality with equivalent positive and negative charged groups, are well known for their superior antifouling properties and have been broadly utilized to construct antifouling surfaces for medical devices, biosensors and marine coatings applications. In recent years, zwitterionic materials have been more and more frequently utilized for constructing antifouling membrane surfaces. In this review, the antifouling mechanisms of zwitterionic materials as well as their biomimetic prototypes in cell membranes will be discussed, followed by the survey of common approaches to incorporate zwitterionic materials onto membrane surfaces including surface grafting, surface segregation, biomimetic adhesion, surface coating and so on. The potential applications of these antifouling membranes are also embedded. Finally, we will present a brief perspective on the future development of zwitterionic materials modified antifouling membranes. Membrane fouling is a severe problem hampering the application of membrane separation technology. The properties of membrane surfaces play a critical role in membrane fouling and antifouling behavior/performance. Antifouling membrane surface construction has evolved as a hot research issue for the development of membrane processes. Zwitterionic modification of membrane surfaces has been recognized as an effective strategy to resist membrane fouling. This review summarizes the antifouling mechanisms of zwitterionic materials inspired by cell membranes as well as the popular approaches to incorporate them onto membrane surfaces. It can help form a comprehensive knowledge about the principles and methods of modifying membrane surfaces with zwitterionic materials. Finally, we propose the possible future research directions of zwitterionic materials modified antifouling membranes. Copyright © 2016 Acta Materialia Inc

  16. Cell Nucleus-Targeting Zwitterionic Carbon Dots.

    Science.gov (United States)

    Jung, Yun Kyung; Shin, Eeseul; Kim, Byeong-Su

    2015-12-22

    An innovative nucleus-targeting zwitterionic carbon dot (CD) vehicle has been developed for anticancer drug delivery and optical monitoring. The zwitterionic functional groups of the CDs introduced by a simple one-step synthesis using β-alanine as a passivating and zwitterionic ligand allow cytoplasmic uptake and subsequent nuclear translocation of the CDs. Moreover, multicolor fluorescence improves the accuracy of the CDs as an optical code. The CD-based drug delivery system constructed by non-covalent grafting of doxorubicin, exhibits superior antitumor efficacy owing to enhanced nuclear delivery in vitro and tumor accumulation in vivo, resulting in highly effective tumor growth inhibition. Since the zwitterionic CDs are highly biocompatible and effectively translocated into the nucleus, it provides a compelling solution to a multifunctional nanoparticle for substantially enhanced nuclear uptake of drugs and optical monitoring of translocation.

  17. Interaction of primaquine and chloroquine with ionic micelles: 1 H NMR and electronic absorption spectroscopy

    International Nuclear Information System (INIS)

    Perussi, Janice R.; Monte, Shirley C.; Imasato, Hidetake; Tabak, Marcel; Yushmanov, Victor E.

    1995-01-01

    The characteristic of binding of primaquine (PQ) and chloroquine (CQ) to micelles of surfactants with different charge of headgroups were studied by 1 H-NMR and optical absorption spectroscopy. Cetyltrimethylammonium (CTAC) was used as a cationic surfactant, sodium dodecylsulfate (SDS) as an anionic surfactant and N-hexadecyl-N, N-dimethyl-3-ammonio-1-propanesulfonate (HPS) as zwitterionic. The pK values and binding constants were estimated. (author)

  18. High-resolution NMR structure of the antimicrobial peptide protegrin-2 in the presence of DPC micelles

    Energy Technology Data Exchange (ETDEWEB)

    Usachev, K. S., E-mail: k.usachev@kpfu.ru; Efimov, S. V.; Kolosova, O. A.; Filippov, A. V.; Klochkov, V. V. [Kazan Federal University (Russian Federation)

    2015-04-15

    PG-1 adopts a dimeric structure in dodecylphosphocholine (DPC) micelles, and a channel is formed by the association of several dimers but the molecular mechanisms of the membrane damage by non-α-helical peptides are still unknown. The formation of the PG-1 dimer is important for pore formation in the lipid bilayer, since the dimer can be regarded as the primary unit for assembly into the ordered aggregates. It was supposed that only 12 residues (RGGRL-CYCRR-RFCVC-V) are needed to endow protegrin molecules with strong antibacterial activity and that at least four additional residues are needed to add potent antifungal properties. Thus, the 16-residue protegrin (PG-2) represents the minimal structure needed for broad-spectrum antimicrobial activity encompassing bacteria and fungi. As the peptide conformation and peptide-to-membrane binding properties are very sensitive to single amino acid substitutions, the solution structure of PG-2 in solution and in a membrane mimicking environment are crucial. In order to find evidence if the oligomerization state of PG-1 in a lipid environment will be the same or not for another protegrins, we investigate in the present work the PG-2 NMR solution structure in the presence of perdeuterated DPC micelles. The NMR study reported in the present work indicates that PG-2 form a well-defined structure (PDB: 2MUH) composed of a two-stranded antiparallel β-sheet when it binds to DPC micelles.

  19. Cell membrane-inspired polymeric micelles as carriers for drug delivery.

    Science.gov (United States)

    Liu, Gongyan; Luo, Quanqing; Gao, Haiqi; Chen, Yuan; Wei, Xing; Dai, Hong; Zhang, Zongcai; Ji, Jian

    2015-03-01

    In cancer therapy, surface engineering of drug delivery systems plays an essential role in their colloidal stability, biocompatibility and prolonged blood circulation. Inspired by the cell membrane consisting of phospholipids and glycolipids, a zwitterionic phosphorylcholine functionalized chitosan oligosaccharide (PC-CSO) was first synthesized to mimic the hydrophilic head groups of those amphipathic lipids. Then hydrophobic stearic acid (SA) similar to lipid fatty acids was grafted onto PC-CSO to form amphiphilic PC-CSO-SA copolymers. Cell membrane-mimetic micelles with a zwitterionic surface and a hydrophobic SA core were prepared by the self-assembly of PC-CSO-SA copolymers, showing excellent stability under extreme conditions including protein containing media, high salt content or a wide pH range. Doxorubicin (DOX) was successfully entrapped into polymeric micelles through the hydrophobic interaction between DOX and SA segments. After fast internalization by cancer cells, sustained drug release from micelles to the cytoplasm and nucleus was achieved. This result suggests that these biomimetic polymeric micelles may be promising drug delivery systems in cancer therapy.

  20. Modeling of chemical reactions in micelle: water-mediated keto-enol interconversion as a case study.

    Science.gov (United States)

    Marracino, Paolo; Amadei, Andrea; Apollonio, Francesca; d'Inzeo, Guglielmo; Liberti, Micaela; di Crescenzo, Antonello; Fontana, Antonella; Zappacosta, Romina; Aschi, Massimiliano

    2011-06-30

    The effect of a zwitterionic micelle environment on the efficiency of the keto-enol interconversion of 2-phenylacetylthiophene has been investigated by means of a joint application of experimental and theoretical/computational approaches. Results have revealed a reduction of the reaction rate constant if compared with bulk water essentially because of the different solvation conditions experienced by the reactant species, including water molecules, in the micelle environment. The slight inhibiting effect due to the application of a static electric field has also been theoretically investigated and presented.

  1. Controllable self-assembly of sodium caseinate with a zwitterionic vitamin-derived bolaamphiphile.

    Science.gov (United States)

    Sun, Li-Hui; Sun, Yu-Long; Yang, Li-Jun; Zhang, Jian; Chen, Zhong-Xiu

    2013-11-06

    The control of self-assembly of sodium caseinate (SC) including the formation of mixed layers, microspheres, or nanoparticles is highly relevant to the microstructure of food and the design of promising drug delivery systems. In this paper, we designed a structure-switchable zwitterionic bolaamphiphile, 1,12-diaminododecanediorotate (DDO), from orotic acid, which has special binding sites and can guide the self-assembly of SC. Complexation between SC and DDO was investigated using dynamic light scattering, transmission electron microscopy, differential scanning calorimetry, and fluorescence spectra measurements. Monomeric DDO was bound to the negatively charged sites on the SC micelle and made the structure of SC more compact with decreased electrostatic repulsion between the head groups. Vesicular DDO led to reassociation of vesicles with enlarged size via preferable hydrophobic interactions. Moreover, the aggregation between SC and DDO was found to be temperature-dependent and reversible. This research provides an effective way to control the reversible self-assembly of SC by the zwitterionic vitamin-derived bolaamphiphile.

  2. Alkylation of Zwitterionic Thiooxalic Acid Derivatives

    Directory of Open Access Journals (Sweden)

    Manfred Michalik

    2001-05-01

    Full Text Available The new S-alkyl thiooxal-1-hydrazono-2-amidrazonium halides 2-4 were synthesized by reaction of the corresponding zwitterionic thiooxalic acid derivatives 1 with alkyl halides in methanol. The structures of compounds 4b and 4d were proven by X-ray structural analysis. Both compounds form an interesting intermolecular network of hydrogen bonds in the solid state.

  3. Reactivity in inverse micelles

    International Nuclear Information System (INIS)

    Brochette, Pascal

    1987-01-01

    This research thesis reports the study of the use of micro-emulsions of water in oil as reaction support. Only the 'inverse micelles' domain of the ternary mixing (water/AOT/isooctane) has been studied. The main addressed issues have been: the micro-emulsion disturbance in presence of reactants, the determination of reactant distribution and the resulting kinetic theory, the effect of the interface on electron transfer reactions, and finally protein solubilization [fr

  4. A molecular receptor selective for zwitterionic alanine.

    Science.gov (United States)

    Rubio, Omayra H; Taouil, Rachid; Muñiz, Francisco M; Monleón, Laura M; Simón, Luis; Sanz, Francisca; Morán, Joaquín R

    2017-01-04

    A molecular receptor has been synthesized joining an aza-crown ether with a chiral chromane which mimics the oxyanion hole of the enzymes. With this receptor an apolar host-guest complex with zwitterionic alanine has been achieved through the formation of up to seven H-bonds. This complex allows the extraction of aqueous alanine to a chloroform phase, while other natural amino acids are poorly extracted or are not extracted at all. Due to the chiral nature of the receptor, enantioselective extraction from the aqueous alanine solution to a chloroform phase takes place. X-Ray analysis combined with anisotropic effects, NOE and CD studies revealed the absolute configuration of both strong and weak complexes. Modelling studies also support the proposed structures. The presence of an oxyanion-hole motif in this structure was corroborated by X-ray diffraction studies.

  5. Enzymatic reactions in reversed micelles

    NARCIS (Netherlands)

    Hilhorst, M.H.

    1984-01-01

    It has been recognised that enzymes in reversed micelles have potential for application in chemical synthesis. Before these expectations will be realised many problems must be overcome. This thesis deals with some of them.
    In Chapter 1 the present knowledge about reversed micelles and

  6. Gas sorption properties of zwitterion-functionalized carbon nanotubes

    Energy Technology Data Exchange (ETDEWEB)

    Surapathi, Anil; Chen, Hang-yan; Marand, Eva; Karl Johnson, J.; Sedlakova, Zdenka

    2013-02-01

    We have functionalized carbon nanotubes with carboxylic acid and zwitterion groups. We have evaluated the effect of functionalization by measuring the sorption of CO{sub 2}, CH{sub 4}, and N{sub 2} at 35°C for pressures up to 10 bar. Zwitterion functionalized nanotubes were found to be highly hygroscopic. Thermal gravimetric analysis indicates that water can be desorbed at about 200°C. The adsorption of gases in zwitterion functionalized nanotubes is dramatically reduced compared with nanotubes functionalized with carboxylic acid groups. The presence of water on the zwitterion functionalized nanotube reduces the sorption even further. Molecular simulations show that three or more zwitterion groups per tube entrance are required to significantly reduce the flux of CO{sub 2} into the tubes. Simulations also show that gas phase water is rapidly sorbed into the zwitterion functionalized nanotubes, both increasing the free energy barrier to CO{sub 2} entering the tube and also lowering the equilibrium adsorption through competitive adsorption.

  7. Supercritical fluid reverse micelle separation

    Science.gov (United States)

    Fulton, J.L.; Smith, R.D.

    1993-11-30

    A method of separating solute material from a polar fluid in a first polar fluid phase is provided. The method comprises combining a polar fluid, a second fluid that is a gas at standard temperature and pressure and has a critical density, and a surfactant. The solute material is dissolved in the polar fluid to define the first polar fluid phase. The combined polar and second fluids, surfactant, and solute material dissolved in the polar fluid is maintained under near critical or supercritical temperature and pressure conditions such that the density of the second fluid exceeds the critical density thereof. In this way, a reverse micelle system defining a reverse micelle solvent is formed which comprises a continuous phase in the second fluid and a plurality of reverse micelles dispersed in the continuous phase. The solute material is dissolved in the polar fluid and is in chemical equilibrium with the reverse micelles. The first polar fluid phase and the continuous phase are immiscible. The reverse micelles each comprise a dynamic aggregate of surfactant molecules surrounding a core of the polar fluid. The reverse micelle solvent has a polar fluid-to-surfactant molar ratio W, which can vary over a range having a maximum ratio W[sub o] that determines the maximum size of the reverse micelles. The maximum ratio W[sub o] of the reverse micelle solvent is then varied, and the solute material from the first polar fluid phase is transported into the reverse micelles in the continuous phase at an extraction efficiency determined by the critical or supercritical conditions. 27 figures.

  8. 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.

  9. Tuning the probe location on zwitterionic micellar system with variation of pH and addition of surfactants with different alkyl chains: solvent and rotational relaxation studies.

    Science.gov (United States)

    Banerjee, Chiranjib; Mandal, Sarthak; Ghosh, Surajit; Rao, Vishal Govind; Sarkar, Nilmoni

    2012-09-13

    In this manuscript, we have modulated the location of an anionic probe, Coumarin-343 (C-343) in a zwitterionic (N-hexadecyl-N,N-dimethylammonio-1-propanesulfonate (SB-16)) micellar system by three different approaches. The effect of addition of the surfactant sodium dodecyl sulfate (SDS) and the room temperature ionic liquid (RTIL), 1-ethyl-3-methylimidazolium octylsulfate (EmimOs) and N,N-dimethylethanol hexanoate (DAH), to the micellar solution has been studied. The effect of pH variation has been studied as well using solvent and rotational measurements. Migration of the anionic probe, C-343, from the palisade layer of SB-16 micelle to the bulk water has been observed to varying extents with the addition of SDS and EmimOs. The effect is much more pronounced in the presence of SDS and can be ascribed to the presence of the long alkyl (dodecyl) chain on SDS which can easily orient itself and fuse inside the SB-16 micelle and facilitate the observed migration of the probe molecule. This phenomenon is confirmed by faster solvation and rotational relaxation of the investigated probe molecule. The analogous fusion process is difficult in case of EmimOs and DAH because of their comparatively smaller alkyl (octyl and hexanoate) chain. However, the direction of C-343 migration is reversed with the decrease of pH of the SB-16 micellar medium. An increase in the average solvation and rotational relaxation time of the probe in acidic medium has been observed. Since experimental conditions are maintained such that the probe molecules and the zwitterionic SB-16 micelles remain oppositely charged, the observed results can be attributed to the increased electrostatic interaction (attractive) between them. Temperature dependent study also supports this finding.

  10. New zwitterionic monoterpene indole alkaloids from Uncaria rhynchophylla.

    Science.gov (United States)

    Guo, Qiang; Yang, Hongshuai; Liu, Xinyu; Si, Xiali; Liang, Hong; Tu, Pengfei; Zhang, Qingying

    2018-01-31

    Four new zwitterionic monoterpene indole alkaloids, rhynchophyllioniums A-D (1-4), together with eight known alkaloids (5-12), were isolated from the hook-bearing stems of Uncaria rhynchophylla. Their structures were elucidated by extensive spectroscopic data analysis of MS, 1D and 2D NMR, and ECD, and the zwitterionic forms and absolute configurations of 1 and 2 were unambiguously confirmed by single crystal X-ray diffraction analysis. All the isolates, including the monoterpene indole alkaloids with free C-22 carboxyl group and those with C-22 carboxyl methyl ester, were proved to be naturally coexisting in the herb by LC-MS analysis. This is the first report of monoterpene indole alkaloids that exist in the form of zwitterion. Additionally, the cytotoxic activities of all isolates against A549, HepG2, and MCF-7 cell lines are reported. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. Gas sorption properties of zwitterion-functionalized carbon nanotubes

    Czech Academy of Sciences Publication Activity Database

    Surapathi, A.; Chen, H.-Y.; Marand, E.; Johnson, J. K.; Sedláková, Zdeňka

    2013-01-01

    Roč. 429, 15 February (2013), s. 88-94 ISSN 0376-7388 R&D Projects: GA MŠk ME09058 Institutional support: RVO:61389013 Keywords : carbon nanotube * zwitterion functionalized membrane * adsorption of gas es Subject RIV: CD - Macromolecular Chemistry Impact factor: 4.908, year: 2013

  12. Sulfobetaine as a zwitterionic mediator for 3D hydroxyapatite mineralization.

    Science.gov (United States)

    Liu, Pingsheng; Song, Jie

    2013-03-01

    Both positively and negatively charged residues play pivotal roles in recruiting precursor ions or ion clusters, and lowering interfacial energy in natural biomineralization process. Synergistic utilization of opposite charges, however, has rarely been implemented in the design of cytocompatible synthetic scaffolds promoting hydroxyapatite (HA)-mineralization and osteointegration. We report the use of cytocompatible zwitterionic sulfobetaine ligands to enable 3-dimensional in vitro mineralization of HA across covalently crosslinked hydrogels. The overall charge-neutral zwitterionic hydrogel effectively recruited oppositely charged precursor ions while overcame excessive swelling exhibited by anionic and cationic hydrogels under physiological conditions, resulting in denser and structurally well-integrated mineralized composites. Further controls over the size, content, and spatial distribution of the mineral domains within the zwitterionic hydrogel are accomplished by facile adjustments of hydrogel crosslinking densities and the supersaturation rate governing heterogeneous mineral nucleation and growth. These findings should inspire many creative uses of zwitterionic polymers and polymer coatings for skeletal tissue repair and regeneration. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. Rapid, facile synthesis of conjugated polymer zwitterions in ionic liquids

    Energy Technology Data Exchange (ETDEWEB)

    Page, Zachariah A. [Polymer Science & Engineering Department; Conte Center for Polymer Research; University of Massachusetts; Amherst, USA; Liu, Feng [Polymer Science & Engineering Department; Conte Center for Polymer Research; University of Massachusetts; Amherst, USA; Russell, Thomas P. [Polymer Science & Engineering Department; Conte Center for Polymer Research; University of Massachusetts; Amherst, USA; Emrick, Todd [Polymer Science & Engineering Department; Conte Center for Polymer Research; University of Massachusetts; Amherst, USA

    2014-01-01

    Ionic liquids (ILs) were utilized for the rapid air-stable Suzuki polymerization of polar zwitterionic thiophene monomers, precluding the need for volatile organic solvents, phosphine ligands and phase transfer catalysts typically used in conjugated polymer synthesis.

  14. Micelle assisted thin-film solid phase microextraction: a new approach for determination of quaternary ammonium compounds in environmental samples.

    Science.gov (United States)

    Boyacı, Ezel; Pawliszyn, Janusz

    2014-09-16

    Determination of quaternary ammonium compounds (QACs) often is considered to be a challenging undertaking owing to secondary interactions of the analytes' permanently charged quaternary ammonium head or hydrophobic tail with the utilized labware. Here, for the first time, a micelle assisted thin-film solid phase microextraction (TF-SPME) using a zwitterionic detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS) as a matrix modifier is introduced as a novel approach for in-laboratory sample preparation of the challenging compounds. The proposed micelle assisted TF-SPME method offers suppression/enhancement free electrospray ionization of analytes in mass spectrometric detection, minimal interaction of the micelles with the TF-SPME coating, and chromatographic stationary phase and analysis free of secondary interactions. Moreover, it was found that the matrix modifier has multiple functions; when its concentration is found below the critical micelle concentration (CMC), the matrix modifier primarily acts as a surface deactivator; above its CMC, it acts as a stabilizer for QACs. Additionally, shorter equilibrium extraction times in the presence of the modifier demonstrated that micelles also assist in the transfer of analytes from the bulk of the sample to the surface of the coating. The developed micelle assisted TF-SPME protocol using the 96-blade system requires only 30 min of extraction and 15 min of desorption. Together with a conditioning step (15 min), the entire method is 60 min; considering the advantage of using the 96-blade system, if all the blades in the brush are used, the sample preparation time per sample is 0.63 min. Moreover, the recoveries for all analytes with the developed method were found to range within 80.2-97.3%; as such, this method can be considered an open bed solid phase extraction. The proposed method was successfully validated using real samples.

  15. Spectroscopic investigation of the pH controlled inclusion of doxycycline and oxytetracycline antibiotics in cationic micelles and their magnesium driven release.

    Science.gov (United States)

    Cesaretti, Alessio; Carlotti, Benedetta; Gentili, Pier Luigi; Clementi, Catia; Germani, Raimondo; Elisei, Fausto

    2014-07-24

    This work presents a steady-state and time-resolved UV-visible spectroscopic investigation of two antibiotics belonging to the family of tetracyclines (doxycycline and oxytetracycline) in the micellar medium provided by p-dodecyloxybenzyltrimethylammonium bromide (pDoTABr). The spectroscopic analysis has been performed in absorption and emission with femtosecond time resolution, and at pH 5.0 and 8.7 where doxycycline and oxytetracycline are present in their neutral-zwitterionic and monoanionic forms, respectively. The experimental data have been processed by sophisticated data mining methods such as global/target analysis and the maximum entropy method. The results unambiguously indicate that, when doxycycline and oxytetracycline are in their zwitterionic form, they are entrapped within the micelle, while when they are in their monoanionic form, they preferentially show a strong one-to-one interaction with the positively charged surfactant heads. Thus, the pH of the solution controls the inclusion of the investigated drugs into the micelle. When the drugs are entrapped inside the micelles, their spectroscopic and dynamical properties after photoexcitation change appreciably. Interestingly, the entrapped drugs are still able to strongly bind Mg(2+) cations, crucial in determining the biological functioning of tetracyclines. The femtosecond resolved measurements reveal that the drugs are efficiently pulled out of the micelles by Mg(2+). In fact, magnesium-tetracycline complexes are detected in the aqueous phase. The present study suggests the potential promising use of ammonium surfactant micelles embedding doxycycline and oxytetracycline as "smart" drug delivery systems allowing their pH controlled inclusion and Mg(2+) induced release.

  16. Polymeric micelles for drug targeting.

    Science.gov (United States)

    Mahmud, Abdullah; Xiong, Xiao-Bing; Aliabadi, Hamidreza Montazeri; Lavasanifar, Afsaneh

    2007-11-01

    Polymeric micelles are nano-delivery systems formed through self-assembly of amphiphilic block copolymers in an aqueous environment. The nanoscopic dimension, stealth properties induced by the hydrophilic polymeric brush on the micellar surface, capacity for stabilized encapsulation of hydrophobic drugs offered by the hydrophobic and rigid micellar core, and finally a possibility for the chemical manipulation of the core/shell structure have made polymeric micelles one of the most promising carriers for drug targeting. To date, three generations of polymeric micellar delivery systems, i.e. polymeric micelles for passive, active and multifunctional drug targeting, have arisen from research efforts, with each subsequent generation displaying greater specificity for the diseased tissue and/or targeting efficiency. The present manuscript aims to review the research efforts made for the development of each generation and provide an assessment on the overall success of polymeric micellar delivery system in drug targeting. The emphasis is placed on the design and development of ligand modified, stimuli responsive and multifunctional polymeric micelles for drug targeting.

  17. Crystal engineering of a zwitterionic drug to neutral cocrystals: a general solution for floxacins.

    Science.gov (United States)

    Gunnam, Anilkumar; Suresh, Kuthuru; Ganduri, Ramesh; Nangia, Ashwini

    2016-10-18

    The transformation of zwitterionic Sparfloxacin (SPX) to the neutral form is achieved by cocrystallization. Neutral forms of drugs are important for higher membrane permeability, while zwitterions are more soluble in water. The twin advantages of higher solubility/dissolution rate and good stability of neutral SPX are achieved in a molecular cocrystal compared to its zwitterionic SPX hydrate. The amine-phenol supramolecular synthon drives cocrystal formation, with the paraben ester acting as a "proton migrator" for the ionic to neutral transformation.

  18. A zwitterionic gel electrolyte for efficient solid-state supercapacitors

    Science.gov (United States)

    Peng, Xu; Liu, Huili; Yin, Qin; Wu, Junchi; Chen, Pengzuo; Zhang, Guangzhao; Liu, Guangming; Wu, Changzheng; Xie, Yi

    2016-01-01

    Gel electrolytes have attracted increasing attention for solid-state supercapacitors. An ideal gel electrolyte usually requires a combination of advantages of high ion migration rate, reasonable mechanical strength and robust water retention ability at the solid state for ensuring excellent work durability. Here we report a zwitterionic gel electrolyte that successfully brings the synergic advantages of robust water retention ability and ion migration channels, manifesting in superior electrochemical performance. When applying the zwitterionic gel electrolyte, our graphene-based solid-state supercapacitor reaches a volume capacitance of 300.8 F cm−3 at 0.8 A cm−3 with a rate capacity of only 14.9% capacitance loss as the current density increases from 0.8 to 20 A cm−3, representing the best value among the previously reported graphene-based solid-state supercapacitors, to the best of our knowledge. We anticipate that zwitterionic gel electrolyte may be developed as a gel electrolyte in solid-state supercapacitors. PMID:27225484

  19. Responsive micellar films of amphiphilic block copolymer micelles: control on micelle opening and closing.

    Science.gov (United States)

    Chen, Zhiquan; He, Changcheng; Li, Fengbin; Tong, Ling; Liao, Xingzhi; Wang, Yong

    2010-06-01

    We reported the deliberate control on the micelle opening and closing of amphiphilic polystyrene-block-poly(2-vinylpyridine) (PS-b-P2VP) micellar films by exposing them to selective solvents. We first treated the micellar films with polar solvents including ethanol and water (pH = 4, 8, and 12) that have different affinities to P2VP. We observed opening of the micelles in all the cases. Both the size of opened pores and the opening rate are dependent on the solvency of different solvents for P2VP. We then explored the closing behavior of the opened micelles using solvents having different affinities to PS. We found that the opened micelles were recovered to their initial closed micelle forms. The recovery was accompanied by a slow micelle disassociation process which gradually reduced the micelle size. The rates of the micelle closing and disassociation are also dependent on the solvency of different solvents for PS.

  20. Recombinant Amphiphilic Protein Micelles for Drug Delivery

    OpenAIRE

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

    2011-01-01

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

  1. Thermodynamics and Structural Evolution during a Reversible Vesicle-Micelle Transition of a Vitamin-Derived Bolaamphiphile Induced by Sodium Cholate.

    Science.gov (United States)

    Tian, Jun-Nan; Ge, Bing-Qiang; Shen, Yun-Feng; He, Yu-Xuan; Chen, Zhong-Xiu

    2016-03-09

    Interaction of endogenous sodium cholate (SC) with dietary amphiphiles would induce structural evolution of the self-assembled aggregates, which inevitably affects the hydrolysis of fat in the gut. Current work mainly focused on the interaction of bile salts with classical double-layered phospholipid vesicles. In this paper, the thermodynamics and structural evolution during the interaction of SC with novel unilamellar vesicles formed from vitamin-derived zwitterionic bolaamphiphile (DDO) were characterized. It was revealed that an increased temperature and the presence of NaCl resulted in narrowed micelle-vesicle coexistence and enlarged the vesicle region. The coexistence of micelles and vesicles mainly came from the interaction of monomeric SC with DDO vesicles, whereas micellar SC contributed to the total solubilization of DDO vesicles. This research may enrich the thermodynamic mechanism behind the structure transition of the microaggregates formed by amphiphiles in the gut. It will also contribute to the design of food formulation and drug delivery system.

  2. A zwitterionic macro-crosslinker for durable non-fouling coatings.

    Science.gov (United States)

    Wang, Wei; Lu, Yang; Xie, Jinbing; Zhu, Hui; Cao, Zhiqiang

    2016-03-28

    A novel zwitterionic macro-crosslinker was developed and applied to fabricate durable non-fouling coatings on a polyurethane substrate. The zwitterionic macro-crosslinker coating exhibited superior durability over the traditional brush polymer coating and was able to retain its non-fouling property even after weeks of shearing in flowing liquid.

  3. Zwitterion enhanced performance in palladium-​phosphine catalyzed ethylene methoxycarbonylation

    DEFF Research Database (Denmark)

    Khokarale, Santosh Govind; Garcia-Suarez, Eduardo J.; Xiong, Jianmin

    2014-01-01

    Zwitterions were used for the first time as promoters in ethylene methoxycarbonylation for the production of methyl propionate. They were found to improve the catalytic performance of the Pd–phosphine system. The presence of zwitterions could contribute to stabilize transition states and active...

  4. Swelling dynamics of zwitterionic copolymers: The effects of concentration and type of anion and cation

    NARCIS (Netherlands)

    de Grooth, Joris; Ogieglo, Wojciech; de Vos, Wiebe Matthijs; Girones nogue, Miriam; Nijmeijer, Dorothea C.; Benes, Nieck Edwin

    2014-01-01

    The effect of different salts and their concentration on the swelling of zwitterionic copolymers has been investigated for bulk polymer samples as well as for thin films. Relatively low ratios of the zwitterionic monomer already radically change the swelling properties of the copolymer. Increasing

  5. Relaxation induced optical anisotropy during dynamic overshoot swelling of zwitterionic polymer films

    NARCIS (Netherlands)

    Ogieglo, Wojciech; de Grooth, Joris; Wormeester, Herbert; Wessling, Matthias; Nijmeijer, Dorothea C.; Benes, Nieck Edwin

    2013-01-01

    In-situ spectroscopic ellipsometry was used to investigate the swelling behavior of thin supported zwitterionic polymers based on sulfobetaine methacrylate and n-butylacrylate. This material represents an interesting class of zwitterionic polymers, with large potential in reduction of biofouling of

  6. Vibrational dynamics of ice in reverse micelles

    NARCIS (Netherlands)

    Dokter, A.M.; Petersen, C.; Woutersen, S.; Bakker, H.J.

    2008-01-01

    he ultrafast vibrational dynamics of HDO:D2O ice at 180 K in anionic reverse micelles is studied by midinfrared femtosecond pump-probe spectroscopy. Solutions containing reverse micelles are cooled to low temperatures by a fast-freezing procedure. The heating dynamics of the micellar solutions is

  7. Casein Micelle Dispersions under Osmotic Stress

    Science.gov (United States)

    Bouchoux, Antoine; Cayemitte, Pierre-Emerson; Jardin, Julien; Gésan-Guiziou, Geneviève; Cabane, Bernard

    2009-01-01

    Abstract Casein micelles dispersions have been concentrated and equilibrated at different osmotic pressures using equilibrium dialysis. This technique measured an equation of state of the dispersions over a wide range of pressures and concentrations and at different ionic strengths. Three regimes were found. i), A dilute regime in which the osmotic pressure is proportional to the casein concentration. In this regime, the casein micelles are well separated and rarely interact, whereas the osmotic pressure is dominated by the contribution from small residual peptides that are dissolved in the aqueous phase. ii), A transition range that starts when the casein micelles begin to interact through their κ-casein brushes and ends when the micelles are forced to get into contact with each other. At the end of this regime, the dispersions behave as coherent solids that do not fully redisperse when osmotic stress is released. iii), A concentrated regime in which compression removes water from within the micelles, and increases the fraction of micelles that are irreversibly linked to each other. In this regime the osmotic pressure profile is a power law of the residual free volume. It is well described by a simple model that considers the micelle to be made of dense regions separated by a continuous phase. The amount of water in the dense regions matches the usual hydration of proteins. PMID:19167314

  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. 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.

  10. Surface zwitterionization: Effective method for preventing oral bacterial biofilm formation on hydroxyapatite surfaces

    Science.gov (United States)

    Lee, Myoungjin; Kim, Heejin; Seo, Jiae; Kang, Minji; Kang, Sunah; Jang, Joomyung; Lee, Yan; Seo, Ji-Hun

    2018-01-01

    In this study, we conducted surface zwitterionization of hydroxyapatite (HA) surfaces by immersing them in the zwitterionic polymer solutions to provide anti-bacterial properties to the HA surface. Three different monomers containing various zwitterionic groups, i.e., phosphorylcholine (PC), sulfobetaine (SB), and carboxybetaine (CB), were copolymerized with the methacrylic monomer containing a Ca2+-binding moiety, using the free radical polymerization method. As a control, functionalization of the copolymer containing the Ca2+-binding moiety was synthesized using a hydroxy group. The stable immobilization of the zwitterionic functional groups was confirmed by water contact angle analysis and X-ray photoelectron spectroscopy (XPS) measurement conducted after the sonication process. The zwitterionized HA surface showed significantly decreased protein adsorption, whereas the hydroxyl group-coated HA surface showed limited efficacy. The anti-bacterial adhesion property was confirmed by conducting Streptococcus mutans (S. mutans) adhesion tests for 6 h and 24 h. When furanone C-30, a representative anti-quorum sensing molecule for S. mutans, was used, only a small amount of bacteria adhered after 6 h and the population did not increase after 24 h. In contrast, zwitterionized HA surfaces showed almost no bacterial adhesion after 6 h and the effect was retained for 24 h, resulting in the lowest level of oral bacterial adhesion. These results confirm that surface zwitterionization is a promising method to effectively prevent oral bacterial adhesion on HA-based materials.

  11. Zwitterionic states in gas-phase polypeptide ions revealed by 157-nm ultra-violet photodissociation

    DEFF Research Database (Denmark)

    Kjeldsen, Frank; Silivra, Oleg A; Zubarev, Roman A

    2006-01-01

    carboxylic groups relative to competing COOH losses (45 Da) from neutral carboxylic groups. Loss of CO2 is a strong indication of the presence of a zwitterionic [(+)...(-)...(+)] salt bridge in the gas-phase polypeptide cation. This method provides a tool for studying, for example, the nature of binding...... of the fragment formation should be taken into account. Cations of Trp-cage proteins exist preferentially as zwitterions, with the deprotonation position divided between the Asp9 residue and the C terminus in the ratio 3:2. The majority of dications of the same molecule are not zwitterions. Furthermore, 157-nm...

  12. 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.

  13. Pluronic®-bile salt mixed micelles.

    Science.gov (United States)

    Patel, Vijay; Ray, Debes; Bahadur, Anita; Ma, Junhe; Aswal, V K; Bahadur, Pratap

    2018-06-01

    The present study was aimed to examine the interaction of two bile salts viz. sodium cholate (NaC) and sodium deoxycholate (NaDC) with three ethylene polyoxide-polypropylene polyoxide (PEO-PPO-PEO) triblock copolymers with similar PPO but varying PEO micelles with a focus on the effect of pH on mixed micelles. Mixed micelles of moderately hydrophobic Pluronic ® P123 were examined in the presence of two bile salts and compared with those from very hydrophobic L121 and very hydrophilic F127. Both the bile salts increase the cloud point (CP) of copolymer solution and decreased apparent micelle hydrodynamic diameter (D h ). SANS study revealed that P123 forms small spherical micelles showing a decrease in size on progressive addition of bile salts. The negatively charged mixed micelles contained fewer P123 molecules but progressively rich in bile salt. NaDC being more hydrophobic displays more pronounced effect than NaC. Interestingly, NaC shows micellar growth in acidic media which has been attributed to the formation of bile acids by protonation of carboxylate ion and subsequent solubilization. In contrast, NaDC showed phase separation at higher concentration. Nuclear Overhauser effect spectroscopy (NOESY) experiments provided information on interaction and location of bile salts in micelles. Results are discussed in terms of hydrophobicity of bile salts and Pluronics ® and the site of bile salt in polymer micelles. Proposed molecular interactions are useful to understand more about bile salts which play important role in physiological processes. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. Micelles As Delivery System for Cancer Treatment.

    Science.gov (United States)

    Keskin, Dilek; Tezcaner, Aysen

    2017-01-01

    Micelles are nanoparticles formed by the self-assembly of amphiphilic block copolymers in certain solvents above concentrations called critical micelle concentration (CMC). Micelles are used in different fields like food, cosmetics, medicine, etc. These nanosized delivery systems are under spotlight in the recent years with new achievements in terms of their in vivo stability, ability to protect entrapped drug, release kinetics, ease of cellular penetration and thereby increased therapeutic efficacy. Drug loaded micelles can be prepared by dialysis, oil-in-water method, solid dispersion, freezing, spray drying, etc. The aim of this review is to give an overview of the research on micelles (in vitro, in vivo and clinical) as delivery system for cancer treatment. Passive targeting is one route for accumulation of nanosized micellar drug formulations. Many research groups from both academia and industry focus on developing new strategies for improving the therapeutic efficacy of micellar systems (active targeting to the tumor site, designing multidrug delivery systems for overcoming multidrug resistance or micelles formed by prodrug conjugates, etc). There is only one micellar drug formulation in South Korea that has reached clinical practice. However, there are many untargeted anticancer drug loaded micellar formulations in clinical trials, which have potential for use in clinics. Many more products are expected to be on the market in the near future. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  15. Preparation of dispersible graphene through organic functionalization of graphene using a zwitterion intermediate cycloaddition approach

    NARCIS (Netherlands)

    Zhang, Xiaoyan; Browne, Wesley R.; Feringa, Ben L.

    2012-01-01

    Highly functionalized graphene were obtained through a zwitterion intermediate cycloaddition onto exfoliated graphene flakes under new reaction conditions. The functionalized graphene obtained formed stable dispersions in common solvents, including dimethylformamide (DMF), CHCl3 and water. Its

  16. Mixed-mode chromatography with zwitterionic phosphopeptidomimetic selectors from Ugi multicomponent reaction

    NARCIS (Netherlands)

    Gargano, Andrea F G; Leek, Tomas; Lindner, Wolfgang; Lämmerhofer, Michael

    2013-01-01

    In the present contribution a novel Ugi multicomponent reaction (MCR) was used to generate zwitterionic chromatographic selectors with capability for application in mixed-mode chromatography featuring complementary selectivities in reversed-phase (RP) and hydrophilic interaction liquid

  17. METHOD FOR THE MEASUREMENT OF SITE-SPECIFIC TAUTOMERIC AND ZWITTERIONIC MICROSPECIES EQUILIBRIUM CONSTANTS

    Science.gov (United States)

    We describe a method for the individual measurement of simultaneously occurring, unimolecular, site-specific “microequilibrium” constants as in, for example, prototropic tautomerism and zwitterionic equilibria. Our method represents an elaboration of that of Nygren et al. (Anal. ...

  18. Molecular design of high performance zwitterionic liquids for enhanced heavy-oil recovery processes.

    Science.gov (United States)

    Martínez-Magadán, J M; Cartas-Rosado, A R; Oviedo-Roa, R; Cisneros-Dévora, R; Pons-Jiménez, M; Hernández-Altamirano, R; Zamudio-Rivera, L S

    2018-03-01

    Branched gemini zwitterionic liquids, which contain two zwitterionic moieties of linked quaternary-ammonium and carboxylate groups, are proposed as chemicals to be applied in the Enhanced Oil Recovery (EOR) from fractured carbonate reservoirs. The zwitterionic moieties are bridged between them through an alkyl chain containing 12 ether groups, and each zwitterionic moiety has attached a long alkyl tail including a CC double bond. A theoretical molecular mechanism over which EOR could rest, consisting on both the disaggregation of heavy oil and the reservoir-rock wettability alteration, was suggested. Results show that chemicals can both reduce the viscosity and remove heavy-oil molecules from the rock surface. Copyright © 2018. Published by Elsevier Inc.

  19. Facilitated preparation of bioconjugatable zwitterionic quantum dots using dual-lipid encapsulation.

    Science.gov (United States)

    Shrake, Robert; Demillo, Violeta G; Ahmadiantehrani, Mojtaba; Zhu, Xiaoshan; Publicover, Nelson G; Hunter, Kenneth W

    2015-01-01

    Zwitterionic quantum dots prepared through incorporated zwitterionic ligands on quantum dot surfaces, are being paid significant attention in biomedical applications because of their excellent colloidal stability across a wide pH and ionic strength range, antifouling surface, good biocompatibility, etc. In this work, we report a dual-lipid encapsulation approach to prepare bioconjugatable zwitterionic quantum dots using amidosulfobetaine-16 lipids, dipalmitoyl-sn-glycero-3-phosphoethanolamine lipids with functional head groups, and CuInS2/ZnS quantum dots in a tetrahydrofuran/methanol/water solvent system with sonication. Amidosulfobetaine-16 is a zwitterionic lipid and dipalmitoyl-sn-glycero-3-phosphoethanolamine, with its functional head, provides bioconjugation capability. Under sonication, tetrahydrofuran/methanol containing amidosulfobetaine-16, dipalmitoyl-sn-glycero-3-phosphoethanolamine, and hydrophobic quantum dots are dispersed in water to form droplets. Highly water-soluble tetrahydrofuran/methanol in droplets is further displaced by water, which induces the lipid self-assembling on hydrophobic surface of quantum dots and thus forms water soluble zwitterionic quantum dots. The prepared zwitterionic quantum dots maintain colloidal stability in aqueous solutions with high salinity and over a wide pH range. They are also able to be conjugated with biomolecules for bioassay with minimal nonspecific binding. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. A Lipophilic IR-780 Dye-Encapsulated Zwitterionic Polymer-Lipid Micellar Nanoparticle for Enhanced Photothermal Therapy and NIR-Based Fluorescence Imaging in a Cervical Tumor Mouse Model

    Directory of Open Access Journals (Sweden)

    Santhosh Kalash Rajendrakumar

    2018-04-01

    Full Text Available To prolong blood circulation and avoid the triggering of immune responses, nanoparticles in the bloodstream require conjugation with polyethylene glycol (PEG. However, PEGylation hinders the interaction between the nanoparticles and the tumor cells and therefore limits the applications of PEGylated nanoparticles for therapeutic drug delivery. To overcome this limitation, zwitterionic materials can be used to enhance the systemic blood circulation and tumor-specific delivery of hydrophobic agents such as IR-780 iodide dye for photothermal therapy. Herein, we developed micellar nanoparticles using the amphiphilic homopolymer poly(12-(methacryloyloxydodecyl phosphorylcholine (PCB-lipid synthesized via reversible addition–fragmentation chain transfer (RAFT polymerization. The PCB-lipid can self-assemble into micelles and encapsulate IR-780 dye (PCB-lipid–IR-780. Our results demonstrated that PCB-lipid–IR-780 nanoparticle (NP exhibited low cytotoxicity and remarkable photothermal cytotoxicity to cervical cancer cells (TC-1 upon near-infrared (NIR laser irradiation. The biodistribution of PCB-lipid–IR-780 showed higher accumulation of PCB-lipid–IR-780 than that of free IR-780 in the TC-1 tumor. Furthermore, following NIR laser irradiation of the tumor region, the PCB-lipid–IR-780 accumulated in the tumor facilitated enhanced tumor ablation and subsequent tumor regression in the TC-1 xenograft model. Hence, these zwitterionic polymer-lipid hybrid micellar nanoparticles show great potential for cancer theranostics and might be beneficial for clinical applications.

  1. 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 ...

  2. Development of zwitterionic chromophores for electro-optic applications

    Science.gov (United States)

    Xiong, Ying

    In order to unlock the full potential of the zwitterionic NLO chromophores for electro-optic (EO) applications, a new series of PeQDM chromophores with large first hyperpolarizabilities (beta0 ˜ 600 x 10-30 esu) have been designed and synthesized. A large EO coefficient (r33) of 110 pm/V at 1550 nm has been realized with a 5 wt% (corresponding to 3.8 wt% core content) chromophore doped polymer. The EO study of guest-host polymers reveals that dipolar dye aggregation in a less polar medium is responsible for a low chromophore loading and low EO activity. Modification of NLO chromophore by attaching large dendrons can effectively increase the chromophore loading in a host and improve the poling efficiency. Crosslinkable NLO polymers have also been prepared to improve the temporal stability of the poled noncentrosymmetric order. The following are some important highlights from this thesis work. (1) A series of thermally stable zwitterionic chromophores (PeQDM) with large first hyperpolarizabilities (beta up to -1797 x 10-30 esu) are synthesized in good yields (˜ 50%). The charge-separated ground state is evident by a negative solvatochromism. X-ray crystallographic data further confirms the zwitterionic nature and demonstrates a face-to-face anti-parallel H-aggregation of two monomers due to strong electrostatic interactions between the dipoles. (2) PeQDM chromophores are also NIR fluorescent (lambdaPL ˜ 840-870 nm in solution) and labile to acid, making them potential candidates for NIR pH sensor applications. (3) The hydroxyl-containing PeQDM chromophores are modified with ES-dendron, which exhibit good solubility in solvents and polymers. Self-forming films can be prepared by direct casting or spin-coating of two dendrons modified chromophores (ES-PeQDM-2 and ES-PeQDM-3), in which the chromophore core contents reach 14.9 and 16.9 wt%, respectively. Compared to ES-PeQDM-2 with two dendrons only at the donor part (r33 = 0 pm/V), ES-PeQDM-3 with the bulky ES

  3. In situ electron-beam polymerization stabilized quantum dot micelles.

    Science.gov (United States)

    Travert-Branger, Nathalie; Dubois, Fabien; Renault, Jean-Philippe; Pin, Serge; Mahler, Benoit; Gravel, Edmond; Dubertret, Benoit; Doris, Eric

    2011-04-19

    A polymerizable amphiphile polymer containing PEG was synthesized and used to encapsulate quantum dots in micelles. The quantum dot micelles were then polymerized using a "clean" electron beam process that did not require any post-irradiation purification. Fluorescence spectroscopy revealed that the polymerized micelles provided an organic coating that preserved the quantum dot fluorescence better than nonpolymerized micelles, even under harsh conditions. © 2011 American Chemical Society

  4. Preparation of Polymeric Micelles for use as Carriers of ...

    African Journals Online (AJOL)

    These micelles were characterized by dynamic light scattering, to measure the micelle diameter; by acid-base titration, to determine the percentage of carboxylic groups occupied by the tuberculostatic; by Sudan III solubility tests, to estimate the critical micelle concentration (CMC); and visual control and spectrophotometric ...

  5. Preparation of Polymeric Micelles for Use as Carriers of ...

    African Journals Online (AJOL)

    Erah

    Tropical Journal of Pharmaceutical Research, December 2007; 6 (4): 815-824 ... by the tuberculostatic; by Sudan III solubility tests, to estimate the critical micelle concentration (CMC); ... Furthermore, the micelles were stable in vitro, exhibiting a low level of CMC and stronger anti- ... that take the form of micelles 5, 6, 7, 8.

  6. "Non-equilibrium" block copolymer micelles with glassy cores: a predictive approach based on theory of equilibrium micelles.

    Science.gov (United States)

    Nagarajan, Ramanathan

    2015-07-01

    Micelles generated in water from most amphiphilic block copolymers are widely recognized to be non-equilibrium structures. Typically, the micelles are prepared by a kinetic process, first allowing molecular scale dissolution of the block copolymer in a common solvent that likes both the blocks and then gradually replacing the common solvent by water to promote the hydrophobic blocks to aggregate and create the micelles. The non-equilibrium nature of the micelle originates from the fact that dynamic exchange between the block copolymer molecules in the micelle and the singly dispersed block copolymer molecules in water is suppressed, because of the glassy nature of the core forming polymer block and/or its very large hydrophobicity. Although most amphiphilic block copolymers generate such non-equilibrium micelles, no theoretical approach to a priori predict the micelle characteristics currently exists. In this work, we propose a predictive approach for non-equilibrium micelles with glassy cores by applying the equilibrium theory of micelles in two steps. In the first, we calculate the properties of micelles formed in the mixed solvent while true equilibrium prevails, until the micelle core becomes glassy. In the second step, we freeze the micelle aggregation number at this glassy state and calculate the corona dimension from the equilibrium theory of micelles. The condition when the micelle core becomes glassy is independently determined from a statistical thermodynamic treatment of diluent effect on polymer glass transition temperature. The predictions based on this "non-equilibrium" model compare reasonably well with experimental data for polystyrene-polyethylene oxide diblock copolymer, which is the most extensively studied system in the literature. In contrast, the application of the equilibrium model to describe such a system significantly overpredicts the micelle core and corona dimensions and the aggregation number. The non-equilibrium model suggests ways to

  7. Stability of casein micelles in milk

    Science.gov (United States)

    Tuinier, R.; de Kruif, C. G.

    2002-07-01

    Casein micelles in milk are proteinaceous colloidal particles and are essential for the production of flocculated and gelled products such as yogurt, cheese, and ice-cream. The colloidal stability of casein micelles is described here by a calculation of the pair potential, containing the essential contributions of brush repulsion, electrostatic repulsion, and van der Waals attraction. The parameters required are taken from the literature. The results are expressed by the second osmotic virial coefficient and are quite consistent with experimental findings. It appears that the stability is mainly attributable to a steric layer of κ-casein, which can be described as a salted polyelectrolyte brush.

  8. Structural analysis of zwitterionic liquids vs. homologous ionic liquids

    Science.gov (United States)

    Wu, Boning; Kuroda, Kosuke; Takahashi, Kenji; Castner, Edward W.

    2018-05-01

    Zwitterionic liquids (Zw-ILs) have been developed that are homologous to monovalent ionic liquids (ILs) and show great promise for controlled dissolution of cellulosic biomass. Using both high energy X-ray scattering and atomistic molecular simulations, this article compares the bulk liquid structural properties for novel Zw-ILs with their homologous ILs. It is shown that the significant localization of the charges on Zw-ILs leads to charge ordering similar to that observed for conventional ionic liquids with monovalent anions and cations. A low-intensity first sharp diffraction peak in the liquid structure factor S(q) is observed for both the Zw-IL and the IL. This is unexpected since both the Zw-IL and IL have a 2-(2-methoxyethoxy)ethyl (diether) functional group on the cationic imidazolium ring and ether functional groups are known to suppress this peak. Detailed analyses show that this intermediate range order in the liquid structure arises for slightly different reasons in the Zw-IL vs. the IL. For the Zw-IL, the ether tails in the liquid are shown to aggregate into nanoscale domains.

  9. Diffusion of aqueous solutions of ionic, zwitterionic, and polar solutes

    Science.gov (United States)

    Teng, Xiaojing; Huang, Qi; Dharmawardhana, Chamila Chathuranga; Ichiye, Toshiko

    2018-06-01

    The properties of aqueous solutions of ionic, zwitterionic, and polar solutes are of interest to many fields. For instance, one of the many anomalous properties of aqueous solutions is the behavior of water diffusion in different monovalent salt solutions. In addition, solutes can affect the stabilities of macromolecules such as proteins in aqueous solution. Here, the diffusivities of aqueous solutions of sodium chloride, potassium chloride, tri-methylamine oxide (TMAO), urea, and TMAO-urea are examined in molecular dynamics simulations. The decrease in the diffusivity of water with the concentration of simple ions and urea can be described by a simple model in which the water molecules hydrogen bonded to the solutes are considered to diffuse at the same rate as the solutes, while the remainder of the water molecules are considered to be bulk and diffuse at almost the same rate as pure water. On the other hand, the decrease in the diffusivity of water with the concentration of TMAO is apparently affected by a decrease in the diffusion rate of the bulk water molecules in addition to the decrease due to the water molecules hydrogen bonded to TMAO. In other words, TMAO enhances the viscosity of water, while urea barely affects it. Overall, this separation of water molecules into those that are hydrogen bonded to solute and those that are bulk can provide a useful means of understanding the short- and long-range effects of solutes on water.

  10. Facile modification of electrospun fibrous structures with antifouling zwitterionic hydrogels.

    Science.gov (United States)

    Xu, Tong; Yang, Jing; Zhang, Jiamin; Zhu, Yingnan; Li, Qingsi; Pan, Chao; Zhang, Lei

    2017-12-28

    Electrospinning technology can easily produce different shaped fibrous structures, making them highly valuable to various biomedical applications. However, surface contamination of biomolecules, cells, or blood has emerged as a significant challenge to the success of electrospun devices, especially artificial blood vessels, catheters and wound dressings etc. Many efforts have been made to resist the surface non-specific biomolecules or cells adsorption, but most of them require complex pre-treatment processes, hard-to-remove metal catalysts or rigorous reaction conditions. In addition, the stability of antifouling coatings, especially in complex conditions, is still a major concern. In this work, inspired by the interpenetrating polymer network and reinforced concrete structure, an efficient and facile strategy for modifying hydrophobic electrospun meshes and tubes with antifouling zwitterionic hydrogels has been introduced. The resulting products could efficiently resist the adhesion of proteins, cells, or even fresh whole blood. Meanwhile, they could maintain the shapes and mechanical strength of the original electrospun structures. Furthermore, the hydrogel structures could retain stable in a physiological condition for at least 3 months. This paper provided a general antifouling and hydrophilicity surface modification strategy for various fibrous structures, and could be of great value for many biomedical applications where antifouling properties are critical.

  11. Efficient Preparation of Super Antifouling PVDF Ultrafiltration Membrane with One Step Fabricated Zwitterionic Surface.

    Science.gov (United States)

    Zhao, Xinzhen; He, Chunju

    2015-08-19

    On the basis of the excellent fouling resistance of zwitterionic materials, the super antifouling polyvinylidene fluoride (PVDF) membrane was efficiently prepared though one-step sulfonation of PVDF and polyaniline blend membrane in situ. The self-doped sulfonated polyaniline (SPANI) was generated as a novel zwitterionic polymer to improve the antifouling property of PVDF ultrafiltration membrane used in sewage treatment. Surface attenuated total reflection Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, surface zeta potential, and water contact angle demonstrated the successful fabrication of zwitterionic interface by convenient sulfonation modification. The static adsorption fouling test showed the quantified adsorption mass of bovine serum albumin (BSA) pollutant on the PVDF/SPANI membrane surface decreases to 3(±2) μg/cm(2), and the water flux recovery ratio (FRR) values were no less than 95% for the three model pollutants of BSA, sodium alginate (SA), and humic acid (HA), which were corresponding hydrophobic, hydrophilic, and natural pollutants in sewage, respectively. This Research Article demonstrated the antifouling advantages of zwitterionic SPANI and aimed to provide a simple method for the large scale preparation of zwitterionic antifouling ultrafiltration membranes.

  12. Synthesis and immobilization of polystyreneb-polyvinyltriethoxysilane micelles

    KAUST Repository

    Zhu, Saisai

    2018-01-31

    Diblock copolymers polystyrene-block-polyvinyltriethoxysilane (PS-b-PVTES) were synthesized via atom transfer radical polymerization (ATRP), which self-assembled into spherical micelles in solvent of THF-methanol mixtures. The self-assembled micelles were immobilized by cross-linking reaction of VTES in a shell layer of micelles. The chemical structures of block copolymers and morphology of micelles were characterized in detail. It was found that the size of immobilized micelles was strongly affected by the copolymer concentration, composition of mixture solvent, and block ratios.

  13. Reverse micelles as a tool for probing solvent modulation of protein dynamics: Reverse micelle encapsulated hemoglobin☆

    OpenAIRE

    Roche, Camille J.; Dantsker, David; Heller, Elizabeth R.; Sabat, Joseph E.; Friedman, Joel M.

    2013-01-01

    Hydration waters impact protein dynamics. Dissecting the interplay between hydration waters and dynamics requires a protein that manifests a broad range of dynamics. Proteins in reverse micelles (RMs) have promise as tools to achieve this objective because the water content can be manipulated. Hemoglobin is an appropriate tool with which to probe hydration effects. We describe both a protocol for hemoglobin encapsulation in reverse micelles and a facile method using PEG and cosolvents to mani...

  14. Micelle-encapsulated fullerenes in aqueous electrolytes

    Energy Technology Data Exchange (ETDEWEB)

    Ala-Kleme, T., E-mail: timo.ala-kleme@utu.fi [Department of Chemistry, University of Turku, 20014 Turku (Finland); Maeki, A.; Maeki, R.; Kopperoinen, A.; Heikkinen, M.; Haapakka, K. [Department of Chemistry, University of Turku, 20014 Turku (Finland)

    2013-03-15

    Different micellar particles Mi(M{sup +}) (Mi=Triton X-100, Triton N-101 R, Triton CF-10, Brij-35, M{sup +}=Na{sup +}, K{sup +}, Cs{sup +}) have been prepared in different aqueous H{sub 3}BO{sub 3}/MOH background electrolytes. It has been observed that these particles can be used to disperse the highly hydrophobic spherical [60]fullerene (1) and ellipsoidal [70]fullerene (2). This dispersion is realised as either micelle-encapsulated monomers Mi(M{sup +})1{sub m} and Mi(M{sup +})2{sub m} or water-soluble micelle-bound aggregates Mi(M{sup +})1{sub agg} and Mi(M{sup +})2{sub agg}, where especially the hydration degree and polyoxyethylene (POE) thickness of the micellar particle seems to play a role of vital importance. Further, the encapsulation microenvironment of 1{sub m} was found to depend strongly on the selected monovalent electrolyte cation, i.e., the encapsulated 1{sub m} is accommodated in the more hydrophobic microenvironment the higher the cationic solvation number is. - Highlights: Black-Right-Pointing-Pointer Different micellar particles is used to disperse [60]fullerene and [70]fullerene. Black-Right-Pointing-Pointer Fullerene monomers or aggregates are dispersed encaging or bounding by micelles. Black-Right-Pointing-Pointer Effective facts are hydration degree and polyoxyethylene thickness of micelle.

  15. Hyaluronan polymeric micelles for topical drug delivery

    Czech Academy of Sciences Publication Activity Database

    Šmejkalová, D.; Muthný, T.; Nešporová, K.; Hermannová, M.; Achbergerová, E.; Huerta-Angelesa, G.; Marek Svoboda, M.; Čepa, M.; Machalová, V.; Luptáková, Dominika; Velebný, V.

    2017-01-01

    Roč. 156, JAN 20 (2017), s. 86-96 ISSN 0144-8617 Institutional support: RVO:61388971 Keywords : Skin penetration * Polymeric micelle * Hyaluronan Subject RIV: CE - Biochemistry OBOR OECD: Biochemistry and molecular biology Impact factor: 4.811, year: 2016

  16. SANS analysis of aqueous ionic perfluoropolyether micelles

    CERN Document Server

    Gambi, C M C; Chittofrati, A; Pieri, R; Baglioni, P; Teixeira, J

    2002-01-01

    Preliminary SANS results of ionic chlorine terminated perfluoropolyether micelles in water are given. The experimental spectra have been analyzed by a two-shell ellipsoidal model for the micellar form factor and a screened Coulombic plus hard-sphere repulsion potential for the structure factor. (orig.)

  17. Co-assembly towards Janus micelles

    NARCIS (Netherlands)

    Voets, I.K.; Leermakers, F.A.M.; Keizer, de A.; Charlaganov, M.; Cohen Stuart, M.A.

    2011-01-01

    In this paper, we report on our recent findings concerning the structure of complex coacervate core micelles composed of two types of (complementary) block copolymers. Both copolymers have a polyelectrolyte (one cationic and the other anionic) block combined with a neutral one. The opposite charges

  18. Neutral Polymeric Micelles for RNA Delivery

    Science.gov (United States)

    Lundy, Brittany B.; Convertine, Anthony; Miteva, Martina; Stayton, Patrick S.

    2013-01-01

    RNA interference (RNAi) drugs have significant therapeutic potential but delivery systems with appropriate efficacy and toxicity profiles are still needed. Here, we describe a neutral, ampholytic polymeric delivery system based on conjugatable diblock polymer micelles. The diblock copolymer contains a hydrophilic poly[N-(2-hydroxypropyl) methacrylamide-co-N-(2-(pyridin-2- yldisulfanyl)ethyl)methacrylamide) (poly[HPMA-co-PDSMA]) segment to promote aqueous stability and facilitate thiol-disulfide exchange reactions, and a second ampholytic block composed of propyl acrylic acid (PAA), dimethylaminoethyl methacrylate (DMAEMA), and butyl methacrylate (BMA). The poly[(HPMA-co-PDSMA)-b-(PAA-co-DMAEMA-co-BMA)] was synthesized using Reversible Addition-Fragmentation chain Transfer (RAFT) polymerization with an overall molecular weight of 22,000 g/mol and a PDI of 1.88. Dynamic light scattering and fluorescence measurements indicated that the diblock copolymers self-assemble under aqueous conditions to form polymeric micelles with a hydrodynamic radius and critical micelle concentration of 25 nm and 25 μg/mL respectively. Red blood cell hemolysis experiments show that the neutral hydrophilic micelles have potent membrane destabilizing activity at endosomal pH values. Thiolated siRNA targeting glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was directly conjugated to the polymeric micelles via thiol exchange reactions with the pyridal disulfide groups present in the micelle corona. Maximum silencing activity in HeLa cells was observed at a 1:10 molar ratio of siRNA to polymer following a 48 h incubation period. Under these conditions 90 % mRNA knockdown and 65 % and protein knockdown of at 48 h was achieved with negligible toxicity. In contrast the polymeric micelles lacking a pH-responsive endosomalytic segment demonstrated negligible mRNA and protein knockdown under these conditions. The potent mRNA knockdown and excellent biocompatibility of the neutral siRNA conjugates

  19. Catalytic copolymerization of CO and ethylene with a charge neutral palladium(II) zwitterion.

    Science.gov (United States)

    Lu, Connie C; Peters, Jonas C

    2002-05-15

    The synthesis of a zwitterionic Pd(II) complex supported by an anionic bis(phosphino)borate ligand, Ph(2)B(CH(2)PPh(2))(2) (abbreviated as [Ph(2)BP(2)]), is reported. The new complex, [Ph(2)BP(2)]PdMe(THF), is active for CO and ethylene copolymerization. The copolymerization activity and polyketone molecular weight for the neutral, zwitterionic system are compared with those for the cationic systems [R(2)E(CH(2)PPh(2))(2)PdMe(THF)][B(C(6)F(5))(4)] where ER(2) = SiPh(2) and CH(2). Surprisingly, the more electron rich zwitterionic system is a catalyst of activity comparable to that of the more conventional cationic systems.

  20. Approaching an organic semimetal: Electron pockets at the Fermi level for a p-benzoquinonemonoimine zwitterion

    Energy Technology Data Exchange (ETDEWEB)

    Rosa, Luis G.; Velev, Julian [Department of Physics and Electronics, University of Puerto Rico, Humacao (United States); Institute for Functional Nanomaterials, University of Puerto Rico, San Juan (United States); Department of Physics and Astronomy, Nebraska Center for Materials and Nanoscience, University of Nebraska-Lincoln, NE (United States); Zhang, Zhengzheng [Department of Physics, University of Puerto Rico, Rio Piedras, San Juan (United States); Alvira, Jose; Vega, Omar; Diaz, Gerson [Department of Physics and Electronics, University of Puerto Rico, Humacao (United States); Routaboul, Lucie; Braunstein, Pierre [Laboratoire de Chimie de Coordination, Institut de Chimie (UMR 7177 CNRS), Universite de Strasbourg (France); Doudin, Bernard [Institut de Physique, Applique de Physique et Chimie des Materiaux de Strasbourg, Universite Louis Pasteur Strasbourg (France); Losovyj, Yaroslav B. [Institute for Functional Nanomaterials, University of Puerto Rico, San Juan (United States); J. Bennett Johnston Sr. Center for Advanced Microstructures and Devices, Louisiana State Univ., Baton Rouge, LA (United States); Dowben, Peter A. [Institute for Functional Nanomaterials, University of Puerto Rico, San Juan (United States)

    2012-08-15

    There is compelling evidence of electron pockets, at the Fermi level, in the band structure for an organic zwitterion molecule of the p-benzoquinonemonoimine type. The electronic structure of the zwitterion molecular film has a definite, although small, density of states evident at the Fermi level as well as a nonzero inner potential and thus is very different from a true insulator. In spite of a small Brillouin zone, significant band width is observed in the intermolecular band dispersion. The results demonstrate that Bloch's theorem applies to the wave vector dependence of the electronic band structure formed from the molecular orbitals of adjacent molecules in a molecular thin film of a p-benzoquinonemonoimine type zwitterion. (Copyright copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  1. Controlled synthesis of gold nanostars by using a zwitterionic surfactant.

    Science.gov (United States)

    Casu, Alberto; Cabrini, Elisa; Donà, Alice; Falqui, Andrea; Diaz-Fernandez, Yuri; Milanese, Chiara; Taglietti, Angelo; Pallavicini, Piersandro

    2012-07-23

    By replacing cetyltrimethylammonium bromide (CTAB) with the zwitterionic lauryl sulfobetaine (LSB) surfactant in the classical seed-growth synthesis, monocrystalline gold nanostars (m-NS) and pentatwinned gold asymmetric nanostars (a-NS) were obtained instead of nanorods. The main product under all synthetic conditions was a-NS, which have branches with high aspect ratios (AR), thus leading to LSPR absorptions in the 750-1150 nm range. The percentage of m-NS versus a-NS, the aspect ratio of the a-NS branches, and consequently the position of their LSPR absorption can be finely tuned simply by regulating the concentration of reductant, the concentration of surfactant, or the concentration of the "catalytic" Ag(+) cation. The m-NS have instead shorter and larger branches, the AR of which is poorly influenced by synthetic conditions and displays an LSPR positioned around 700 nm. A growth mechanism that involves the direct contact of the sulfate moiety of LSB on the surface of the nano-object is proposed, thereby implying preferential coating of the {111} Au faces with weak interactions. Consistent with this, we also observed the straightforward complete displacement of the LSB surfactant from the surface of the nanostars. This was obtained by the simple addition of thiols in aqueous solution to yield extremely stable coated a-NS and m-NS that are resistant to highly acidic, basic, and in similar to in vivo conditions. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Effect of hydrostatic pressure on gas solubilization in micelles.

    Science.gov (United States)

    Meng, Bin; Ashbaugh, Henry S

    2015-03-24

    Molecular dynamics simulations of anionic sodium decylsulfate and nonionic pentaethylene glycol monodecyl ether micelles in water have been performed to examine the impact of hydrostatic pressure on argon solubilization as a function of pressure. The potential-of-mean force between the micelles and argon demonstrates that nonpolar gases are attracted to the interiors of both micelles. The affinity of argon for micelle interiors, however, decreases with increasing pressure as a result of the comparatively higher molar volume of argon inside assemblies. We evaluate solubility enhancement coefficients, which describe the drop in the solute chemical potential as a function of the micellized surfactant concentration, to quantify the impact of micellization on gas solubilization. While argon is similarly attracted to the hydrophobic cores of both micelles, the gas is more effectively sequestered within nonionic micelles compared with anionic micelles as a result of salting out by charged head groups and accompanying counterions. The solubility enhancement coefficients of both micelles decrease with increasing pressure, reflecting the changing forces observed in the potentials-of-mean force. An analytical liquid drop model is proposed to describe the pressure dependence of argon solubilization within micelles that captures the simulation solubility enhancement coefficients after fitting an effective micelle radius for each surfactant.

  3. Smart wormlike micelles design, characteristics and applications

    CERN Document Server

    Feng, Yujun; Dreiss, Cécile A

    2015-01-01

    This Brief provides an up-to-date overview of smart surfactants and describes a broad spectrum of triggers that induce the formation of wormlike micelles or reversibly tune the morphology of surfactant aggregates from wormlike micelles to another state, or vice versa. Combining the fields of chemistry, physics, polymer science, and nanotechnology, its primary focus is on the design, formulation, and processing of intelligent viscoelastic surfactant solutions, covering the scientific principles governing responsiveness to one or more particular triggers, down to the end-use-driven functions. The first chapter explains why and how surfactants self-assemble into viscoelastic wormlike micellar solutions reminiscent of polymer solutions, while the following chapters show how the response to a given trigger translates into macroscopic rheological changes, including temperature, light, pH, CO2, redox, hydrocarbon, etc. The last chapter demonstrates the applications of these viscoelastic assemblies in oil and gas pro...

  4. SANS study of coated block copolymer micelles

    Czech Academy of Sciences Publication Activity Database

    Pleštil, Josef; Kříž, Jaroslav; Koňák, Čestmír; Pospíšil, Herman; Kadlec, Petr; Sedláková, Zdeňka; Grillo, I.; Cubitt, R.

    2005-01-01

    Roč. 206, č. 12 (2005), s. 1206-1215 ISSN 1022-1352 R&D Projects: GA ČR GA203/03/0600; GA AV ČR IAA1050201; GA AV ČR KSK4050111 Institutional research plan: CEZ:AV0Z40500505 Keywords : block copolymer micelles * core-shell polymers * nanoparticles Subject RIV: CD - Macromolecular Chemistry Impact factor: 2.111, year: 2005

  5. Thermoresponsive polymer micelles as potential nanosized cancerostatics

    Czech Academy of Sciences Publication Activity Database

    Laga, Richard; Janoušková, Olga; Ulbrich, Karel; Pola, Robert; Blažková, Jana; Filippov, Sergey K.; Etrych, Tomáš; Pechar, Michal

    2015-01-01

    Roč. 16, č. 8 (2015), s. 2493-2505 ISSN 1525-7797 R&D Projects: GA MŠk(CZ) EE2.3.30.0029; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:61389013 Keywords : RAFT polymerization * polymer therapeutics * thermo-responsive micelles Subject RIV: CE - Biochemistry Impact factor: 5.583, year: 2015

  6. Generic Top-Functionalization of Patterned Antifouling Zwitterionic Polymers on Indium Tin Oxide

    NARCIS (Netherlands)

    Li, Y.; Giesbers, M.; Zuilhof, H.

    2012-01-01

    This paper presents a novel surface engineering approach that combines photochemical grafting and surface-initiated atom transfer radical polymerization (SI-ATRP) to attach zwitterionic polymer brushes onto indium tin oxide (ITO) substrates. The photochemically grafted hydroxyl-terminated organic

  7. Selective Interaction of a Cationic Polyfluorene with Model Lipid Membranes: Anionic versus Zwitterionic Lipids

    Directory of Open Access Journals (Sweden)

    Zehra Kahveci

    2014-03-01

    Full Text Available This paper explores the interaction mechanism between the conjugated polyelectrolyte {[9,9-bis(6'-N,N,N-trimethylammoniumhexyl]fluorene-phenylene}bromide (HTMA-PFP and model lipid membranes. The study was carried out using different biophysical techniques, mainly fluorescence spectroscopy and microscopy. Results show that despite the preferential interaction of HTMA-PFP with anionic lipids, HTMA-PFP shows affinity for zwitterionic lipids; although the interaction mechanism is different as well as HTMA-PFP’s final membrane location. Whilst the polyelectrolyte is embedded within the lipid bilayer in the anionic membrane, it remains close to the surface, forming aggregates that are sensitive to the physical state of the lipid bilayer in the zwitterionic system. The different interaction mechanism is reflected in the polyelectrolyte fluorescence spectrum, since the maximum shifts to longer wavelengths in the zwitterionic system. The intrinsic fluorescence of HTMA-PFP was used to visualize the interaction between polymer and vesicles via fluorescence microscopy, thanks to its high quantum yield and photostability. This technique allows the selectivity of the polyelectrolyte and higher affinity for anionic membranes to be observed. The results confirmed the appropriateness of using HTMA-PFP as a membrane fluorescent marker and suggest that, given its different behaviour towards anionic and zwitterionic membranes, HTMA-PFP could be used for selective recognition and imaging of bacteria over mammalian cells.

  8. Superior Antifouling Performance of a Zwitterionic Peptide Compared to an Amphiphilic, Non-Ionic Peptide.

    Science.gov (United States)

    Ye, Huijun; Wang, Libing; Huang, Renliang; Su, Rongxin; Liu, Boshi; Qi, Wei; He, Zhimin

    2015-10-14

    The aim of this study was to explore the influence of amphiphilic and zwitterionic structures on the resistance of protein adsorption to peptide self-assembled monolayers (SAMs) and gain insight into the associated antifouling mechanism. Two kinds of cysteine-terminated heptapeptides were studied. One peptide had alternating hydrophobic and hydrophilic residues with an amphiphilic sequence of CYSYSYS. The other peptide (CRERERE) was zwitterionic. Both peptides were covalently attached onto gold substrates via gold-thiol bond formation. Surface plasmon resonance analysis results showed that both peptide SAMs had ultralow or low protein adsorption amounts of 1.97-11.78 ng/cm2 in the presence of single proteins. The zwitterionic peptide showed relatively higher antifouling ability with single proteins and natural complex protein media. We performed molecular dynamics simulations to understand their respective antifouling behaviors. The results indicated that strong surface hydration of peptide SAMs contributes to fouling resistance by impeding interactions with proteins. Compared to the CYSYSYS peptide, more water molecules were predicted to form hydrogen-bonding interactions with the zwitterionic CRERERE peptide, which is in agreement with the antifouling test results. These findings reveal a clear relation between peptide structures and resistance to protein adsorption, facilitating the development of novel peptide-containing antifouling materials.

  9. Molecular Recognition of Vesicles : Host-Guest Interactions Combined with Specific Dimerization of Zwitterions

    NARCIS (Netherlands)

    Voskuhl, Jens; Fenske, Tassilo; Stuart, Marc C. A.; Wibbeling, Birgit; Schmuck, Carsten; Ravoo, Bart Jan

    2010-01-01

    The aggregation of beta-cyclodextrin vesicles can be induced by an adamantyl-substituted zwitterionic guanidiniocarbonylpyrrole carboxylate guest molecule (1). Upon addition of 1 to the cyclodextrin vesicles at neutral pH, the vesicles aggregate (but do not fuse), as shown by using UV/Vis and

  10. Neutral, anionic, cationic, and zwitterionic diblock copolymers featuring poly(2-methoxyethyl acrylate) hydrophobic segments

    DEFF Research Database (Denmark)

    Javakhishvili, Irakli; Jankova Atanasova, Katja; Hvilsted, Søren

    2013-01-01

    -b-PDMAEMA while the betainisation of the latter provides zwitterionic diblock amphiphile PMEA-b-PDMAPS. Inspection of these macromolecular architectures by NMR spectroscopy and size exclusion chromatography (SEC) confirms a fairly high degree of control over the reactions emphasizing flexibility and precision...

  11. Zwitterions as alternative draw solutions in forward osmosis for application in wastewater reclamation

    NARCIS (Netherlands)

    Lutchmiah, K.; Lauber, L.; Roest, de K.; Harmsen, D.J.H.; Post, J.W.; Rietveld, L.C.; Lier, van J.B.; Cornelissen, E.R.

    2014-01-01

    The draw solution is the driving force in forward osmosis (FO) processes. The reverse solute leakage of the draw solution is however a major constraint due to cost and energy requirements when reconcentrating the solutes subsequent to the FO process. Several zwitterions as draw solutions (pi

  12. Stable Protein-Repellent Zwitterionic Polymer Brushes Grafted from Silicon Nitride

    NARCIS (Netherlands)

    Nguyen, A.T.; Baggerman, J.; Paulusse, J.M.J.; Rijn, van C.J.M.; Zuilhof, H.

    2011-01-01

    Zwitterionic poly(sulfobetaine acrylamide) (SBMAA) brushes were grafted from silicon-rich silicon nitride (SixN4, x > 3) surfaces by atom transfer radical polymerization (ATRP) and studied in protein adsorption experiments. To this aim ATRP initiators were immobilized onto SixN4 through stable

  13. Stable Protein-Repellent Zwitterionic Polymer Brushes Grafted from Silicon Nitride

    NARCIS (Netherlands)

    Nguyen, Ai T.; Baggerman, Jacob; Paulusse, Jos Marie Johannes; van Rijn, Cees J.M.; Zuilhof, Han

    2011-01-01

    Zwitterionic poly(sulfobetaine acrylamide) (SBMAA) brushes were grafted from silicon-rich silicon nitride (SixN4, x > 3) surfaces by atom transfer radical polymerization (ATRP) and studied in protein adsorption experiments. To this aim ATRP initiators were immobilized onto SixN4 through stable Si−C

  14. New Chiral Zwitterionic Phosphorus Heterocycles: Synthesis, Structure, Properties and Application as Chiral Solvating Agents

    Czech Academy of Sciences Publication Activity Database

    Sheshenev, A. E.; Boltukhina, E. V.; Grishina, Anastasia; Císařová, I.; Lyapkalo, Ilya; Hii, K. K.

    2013-01-01

    Roč. 19, č. 25 (2013), s. 8136-8143 ISSN 0947-6539 Grant - others:7th European Community Framework Programme(XE) FP7-252247 Institutional support: RVO:61388963 Keywords : binding constants * chirality * enantioselectivity * NMR spectroscopy * phosphorus heterocycles * zwitterions Subject RIV: CC - Organic Chemistry Impact factor: 5.696, year: 2013

  15. Polymeric micelles as a drug carrier for tumor targeting

    Directory of Open Access Journals (Sweden)

    Neha M Dand

    2013-01-01

    Full Text Available Polymeric micelle can be targeted to tumor site by passive and active mechanism. Some inherent properties of polymeric micelle such as size in nanorange, stability in plasma, longevity in vivo, and pathological characteristics of tumor make polymeric micelles to be targeted at the tumor site by passive mechanism called enhanced permeability and retention effect. Polymeric micelle formed from the amphiphilic block copolymer is suitable for encapsulation of poorly water soluble, hydrophobic anticancer drugs. Other characteristics of polymeric micelles such as separated functionality at the outer shell are useful for targeting the anticancer drug to tumor by active mechanisms. Polymeric micelles can be conjugated with many ligands such as antibodies fragments, epidermal growth factors, α2 -glycoprotein, transferrine, and folate to target micelles to cancer cells. Application of heat and ultrasound are the alternative methods to enhance drug accumulation in tumoral cells. Targeting using micelles can also be done to tumor angiogenesis which is the potentially promising target for anticancer drugs. This review summarizes about recently available information regarding targeting the anticancer drug to the tumor site using polymeric micelles.

  16. 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.

  17. Stereocomplex-Reinforced PEGylated Polylactide Micelle for Optimized Drug Delivery

    Directory of Open Access Journals (Sweden)

    Chunsheng Feng

    2016-04-01

    Full Text Available The instability of PEGylated polylactide micelles is a challenge for drug delivery. Stereocomplex interaction between racemic polylactide chains with different configurations provides an effective strategy to enhance the stability of micelles as the nanocarriers of drugs. In this work, a stereocomplex micelle (SCM self-assembled from the amphiphilic triblock copolymers comprising poly(ethylene glycol (PEG, and dextrorotatory and levorotatory polylactides (PDLA and PLLA was applied for efficient drug delivery. The spherical SCM showed the smallest scale and the lowest critical micelle concentration (CMC than the micelles with single components attributed to the stereocomplex interaction between PDLA and PLLA. 10-Hydroxycamptothecin (HCPT as a model antitumor drug was loaded into micelles. Compared with the loading micelles from individual PDLA and PLLA, the HCPT-loaded SCM exhibited the highest drug loading efficiency (DLE and the slowest drug release in phosphate-buffered saline (PBS at pH 7.4, indicating its enhanced stability in circulation. More fascinatingly, the laden SCM was demonstrated to have the highest cellular uptake of HCPT and suppress malignant cells most effectively in comparison to the HCPT-loaded micelles from single copolymer. In summary, the stereocomplex-enhanced PLA–PEG–PLA micelle may be promising for optimized drug delivery in the clinic.

  18. Selective entrapment of the cationic form of norfloxacin within anionic sodium dodecyl sulfate micelles at physiological pH and its effect on the drug photodecomposition.

    Science.gov (United States)

    Sortino, Salvatore

    2006-01-01

    The binding of the photosensitizing fluoroquinolone (FQ) antibiotic norfloxacin (NX) to sodium dodecyl sulfate (SDS) micelles and the photoreactivity of the NX/SDS complex under physiological pH conditions are investigated by means of absorption and emission spectroscopy, steady-state and laser flash photolysis. It is shown that the photolabile zwitterionic form of NX, which is dominant at physiological pH, is not the most abundant species in the presence of SDS micelles. This medium exhibits a high preference for the cationic form of the drug, which is selectively and successfully entrapped within the micellar cage (K(ass) = 6 x 10(4) M(-1) +/- 3000), becoming the largely dominant species at neutral pH. The effect of this trapping is drastically reflected on both efficiency and nature of the drug photodecomposition. It is observed that the photostability of NX incorporated in the micellar pseudophase increases of more than one order of magnitude if compared to that of the "free" drug. Furthermore, the radical photodecomposition mechanism occurring in phosphate buffered solution is suppressed by the micellar medium and the low photodegradation observed seems to take place preferentially through an ionic pathway. Hopefully, the results presented herein may contribute to a better understanding of the bio-distribution of NX in biological systems and provide helpful and stimulating information in order to get the control of FQ photoreactivity under physiological pH conditions.

  19. 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.

  20. Lactoferrin binding to transglutaminase cross-linked casein micelles

    NARCIS (Netherlands)

    Anema, S.G.; de Kruif, C.G.|info:eu-repo/dai/nl/073609609

    2012-01-01

    Casein micelles in skim milk were either untreated (untreated milk) or were cross-linked using transglutaminase (TGA-milk). Added lactoferrin (LF) bound to the casein micelles and followed Langmuir adsorption isotherms. The adsorption level was the same in both milks and decreased the micellar zeta

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

    NARCIS (Netherlands)

    Lindhoud, Saskia; de Vries, Renko; Norde, Willem; Cohen Stuart, Martinus Abraham

    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

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

    NARCIS (Netherlands)

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

    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)

  3. 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

  4. Characterization of Phospholipid Mixed Micelles by Translational Diffusion

    International Nuclear Information System (INIS)

    Chou, James J.; Baber, James L.; Bax, Ad

    2004-01-01

    The concentration dependence of the translational self diffusion rate, D s , has been measured for a range of micelle and mixed micelle systems. Use of bipolar gradient pulse pairs in the longitudinal eddy current delay experiment minimizes NOE attenuation and is found critical for optimizing sensitivity of the translational diffusion measurement of macromolecules and aggregates. For low volume fractions Φ (Φ ≤ 15% v/v) of the micelles, experimental measurement of the concentration dependence, combined with use of the D s =D o (1-3.2λΦ) relationship, yields the hydrodynamic volume. For proteins, the hydrodynamic volume, derived from D s at infinitely dilute concentration, is found to be about 2.6 times the unhydrated molecular volume. Using the data collected for hen egg white lysozyme as a reference, diffusion data for dihexanoyl phosphatidylcholine (DHPC) micelles indicate approximately 27 molecules per micelle, and a critical micelle concentration of 14 mM. Differences in translational diffusion rates for detergent and long chain phospholipids in mixed micelles are attributed to rapid exchange between free and micelle-bound detergent. This difference permits determination of the free detergent concentration, which, for a high detergent to long chain phospholipid molar ratio, is found to depend strongly on this ratio. The hydrodynamic volume of DHPC/POPC bicelles, loaded with an M2 channel peptide homolog, derived from translational diffusion, predicts a rotational correlation time that slightly exceeds the value obtained from peptide 15 N relaxation data

  5. Design and preparation of bi-functionalized short-chain modified zwitterionic nanoparticles.

    Science.gov (United States)

    Hu, Fenglin; Chen, Kaimin; Xu, Hong; Gu, Hongchen

    2018-05-01

    An ideal nanomaterial for use in the bio-medical field should have a distinctive surface capable of effectively preventing nonspecific protein adsorption and identifying target bio-molecules. Recently, the short-chain zwitterion strategy has been suggested as a simple and novel approach to create outstanding anti-fouling surfaces. In this paper, the carboxyl end group of short-chain zwitterion-coated silica nanoparticles (SiO 2 -ZWS) was found to be difficult to functionalize via a conventional EDC/NHS strategy due to its rapid hydrolysis side-reactions. Hence, a series of bi-functionalized silica nanoparticles (SiO 2 -ZWS/COOH) were designed and prepared by controlling the molar ratio of 3-aminopropyltriethoxysilane (APTES) to short-chain zwitterionic organosiloxane (ZWS) in order to achieve above goal. The synthesized SiO 2 -ZWS/COOH had similar excellent anti-fouling properties compared with SiO 2 -ZWS, even in 50% fetal bovine serum characterized by DLS and turbidimetric titration. Subsequently, SiO 2 -ZWS/COOH 5/1 was chosen as a representative and then demonstrated higher detection signal intensity and more superior signal-to-noise ratios compare with the pure SiO 2 -COOH when they were used as a bio-carrier for chemiluminescence enzyme immunoassay (CLEIA). These unique bi-functionalized silica nanoparticles have many potential applications in the diagnostic and therapeutic fields. Reducing nonspecific protein adsorption and enhancing the immobilized efficiency of specific bio-probes are two of the most important issues for bio-carriers, particularly for a nanoparticle based bio-carrier. Herein, we designed and prepared a bi-functional nanoparticle with anti-fouling property and bio conjugation capacity for further bioassay by improving the short-chain zwitterionic modification strategy we have proposed previously. The heterogeneous surface of this nanoparticle showed effective anti-fouling properties both in model protein solutions and fetal bovine serum

  6. The thermal signature of wormlike micelles

    International Nuclear Information System (INIS)

    Ito, Thiago Heiji; Clinckspoor, Karl Jan; Nunes de Souza, Renato; Sabadini, Edvaldo

    2016-01-01

    Highlights: • Giant micelle formation has a characteristic exothermic profile, for these systems. • The enthalpy of formation is dependent on the planarity of the co-solute. • The affinity is dependent on the enthalpy and critical concentration of the species. • The higher the affinity, the higher thermal stability and size of the micelles. - Abstract: The variations in enthalpy (Δ f H WLM ) and critical concentrations associated with the formation of wormlike micelles (WLMs) from combinations of tetradecyltrimethylammonium bromide (C 14 TAB) and various aromatic co-solutes were determined using isothermal titration calorimetry (ITC). Three groups of aromatic molecules were investigated: neutral (phenol), benzoate derivatives and cinnamate derivatives. In addition, the thermal stabilities of the WLMs (of hexadecyltrimethylammonium bromide, C 16 TAB) and the aromatic co-solutes of the three groups were investigated by measuring the temperatures at which the WLMs break and lose their ability to produce hydrodynamic drag reduction. A comparison of the results was used to establish correlations between the spontaneity of WLMs formation, their thermal stability and the molecular structure of the aromatic co-solutes. A characteristic thermal pattern with four steps was observed when WLMs are formed, that depended on the co-solute structure. Micellar growth was found to be an exothermic process, related to the fusion of the end caps allied with the incorporation of more co-solutes. The co-solutes that had negative charge and were able to maintain planar configuration demonstrated stronger interactions and also showed higher thermal stability through drag reduction.

  7. pH dependent polymeric micelle adsorption

    Energy Technology Data Exchange (ETDEWEB)

    McLean, S C; Gee, M L [The University of Melbourne, VIC (Australia). School of Chemistry

    2003-07-01

    Full text: Poly(2-vinylpyridine)-poly(ethylene oxide) (P2VP-PEO) shows potential as a possible drug delivery system for anti-tumour drugs since it forms pH dependent polymeric micelles. Hence to better understand the adsorption behaviour of this polymer we have studied the interaction forces between layers of P2VP-PEO adsorbed onto silica as a function of solution pH using an Atomic Force Microscope (AFM). When P2VP-PEO is initially adsorbed above the pKa of the P2VP block, P2VP-PEO adsorbs from solution as micelles that exist as either partially collapsed- or a hemi-micelles at the silica surface. Below the pKa of P2VP, the P2VP-PEO adsorbs as unimers, forming a compact layer with little looping and tailing into solution. When initial adsorption of P2VP-PEO is in the form of unimers, any driving force to self-assembly of the now charge neutral polymer is kinetically hindered. Hence, after initial adsorption at pH 3.6, a subsequent increase in pH to 6.6 results in a slow surface restructuring towards self-assembly and equilibrium. When the pH is increased from pH 6.6 to 9.7 there is a continuation of the evolution of the system to its equilibrium position during which the adsorbed P2VP-PEO unimers continue to 'unravel' from the surface, extending away from it, towards eventual complete surface self-assembly.

  8. Reaction of iminopropadienones with amines--formation of zwitterionic intermediates, ketenes, and ketenimines.

    Science.gov (United States)

    Veedu, Rakesh Naduvile; Kokas, Okanya J; Couturier-Tamburelli, Isabelle; Koch, Rainer; Aycard, Jean-Pierre; Borget, Fabien; Wentrup, Curt

    2008-10-09

    Five aryliminopropadienones 4a- d have been synthesized by flash vacuum thermolysis (FVT) by using two different precursors in each case. These compounds were deposited at 50 K at a pressure of ca. 10(-6) mbar together with three different nucleophiles, namely, trimethylamine (TMA), dimethylamine (DMA), and diethylamine (DEA), in order to study their reactions as neat solids during warm-up by FTIR spectroscopy. The reaction with TMA showed that a zwitterionic species (5 and/or 6) was formed in all the cases. With DMA and DEA, an alpha-oxoketenimine and/or an imidoylketene (7 and 8 or 9 and 10) was formed as the final product. In addition, several bands were observed, which can be assigned to zwitterionic intermediates (11 or 12). Optimized structures and vibrational spectra for all products were calculated at the B3LYP/6-31G(d) level of theory by using the polarizable continuum model (epsilon = 5).

  9. Hydrogen-bonded co-crystal structure of benzoic acid and zwitterionic l-proline

    Directory of Open Access Journals (Sweden)

    Aaron M. Chesna

    2017-03-01

    Full Text Available The title compound [systematic name: benzoic acid–pyrrolidin-1-ium-2-carboxylate (1/1], C7H6O2·C5H9NO2, is an example of the application of non-centrosymmetric co-crystallization for the growth of a crystal containing a typically centrosymmetric component in a chiral space group. It co-crystallizes in the space group P212121 and contains benzoic acid and l-proline in equal proportions. The crystal structure exhibits chains of l-proline zwitterions capped by benzoic acid molecules which form a C(5[R33(11] hydrogen-bonded network along [100]. The crystal structure is examined and compared to that of a similar co-crystal containing l-proline zwitterions and 4-aminobenzoic acid.

  10. Synthesis and characterization of a zwitterionic hydrogel blend with low coefficient of friction.

    Science.gov (United States)

    Osaheni, Allen O; Finkelstein, Eric B; Mather, Patrick T; Blum, Michelle M

    2016-12-01

    Hydrogels display a great deal of potential for a wide variety of biomedical applications. Often times the performance of these biomimetic materials is limited due to inferior friction and wear properties. This manuscript presents a method inspired by the tribological phenomena observed in nature for enhancing the lubricious properties of poly(vinyl alcohol) (PVA) hydrogels. This was achieved by blending PVA with various amounts of zwitterionic polymer, poly([2-(methacryloyloxy) ethyl] dimethyl-(3-sulfopropyl) ammonium hydroxide) (pMEDSAH). Our results indicate that pMEDSAH acts as an effective boundary lubricant, allowing for reduction in coefficient of friction by more than 80%. This reduction in friction coefficient was achieved while maintaining comparable mechanical and physical properties to that of the neat material. Also, these zwitterionic blends were found to be cytocompatible. Analysis of the structure to property relationships within this system indicate that the zwitterionic polymer served as a boundary lubricant and promoted a reduction in friction through hydration lubrication. This novel approach provides a promising platform for further investigations enhancing the tribological properties of hydrogels for biomedical applications. The novelty of this work stems from showing that zwitterionic polymers can be used as an extremely effective hydrogel boundary lubricant. This work will have significant scientific impact because to date, design of hydrogels has emphasized replication of mechanical properties, but in order for these types of materials to be fully utilized as biomaterials it is imperative that they possess improved tribological and lubrication properties, because ignoring the surface and boundary lubrication mechanism, make these potential load-bearing substitutes incompatible with other natural articulating surfaces, leading the constructs to wear, fail, and damage healthy tissue. Our work also provides unique insight to the structure

  11. Non-fouling hydrogels of 2-hydroxyethyl methacrylate and zwitterionic carboxybetaine (meth)acrylamides

    Czech Academy of Sciences Publication Activity Database

    Kostina, Nina Yu.; Rodriguez-Emmenegger, Cesar; Houska, Milan; Brynda, Eduard; Michálek, Jiří

    2012-01-01

    Roč. 13, č. 12 (2012), s. 4164-4170 ISSN 1525-7797 R&D Projects: GA AV ČR KAN200520804; GA ČR GAP205/12/1702; GA ČR GAP106/12/1451 Institutional research plan: CEZ:AV0Z40500505 Institutional support: RVO:61389013 Keywords : zwitterionic hydrogels * non-fouling properties * carboxybetaine Subject RIV: CD - Macromolecular Chemistry Impact factor: 5.371, year: 2012

  12. Development of Low Fouling and High Fouling-release Zwitterionic Marine Coatings

    Science.gov (United States)

    2016-01-04

    amount, pigment , crosslinker type and catalyst amount. The details are shown below, 1. PDMS coating with zwitterionic copolymer incorporated. PDMS...onto aluminum panels. The coating can be cured within 3.5 hours. 2. PDMS coating with pigment incorporated. Various amount of the pigment cadmium...stirred vigorously until all the solid were dispersed uniformly. The obtained viscous liquid was then mixed with 3 g PDMS crosslinker, and applied onto

  13. Electronic nature of zwitterionic alkali metal methanides, silanides and germanides - a combined experimental and computational approach.

    Science.gov (United States)

    Li, H; Aquino, A J A; Cordes, D B; Hase, W L; Krempner, C

    2017-02-01

    Zwitterionic group 14 complexes of the alkali metals of formula [C(SiMe 2 OCH 2 CH 2 OMe) 3 M], (M- 1 ), [Si(SiMe 2 OCH 2 CH 2 OMe) 3 M], (M- 2 ), [Ge(SiMe 2 OCH 2 CH 2 OMe) 3 M], (M- 3 ), where M = Li, Na or K, have been prepared, structurally characterized and their electronic nature was investigated by computational methods. Zwitterions M- 2 and M- 3 were synthesized via reactions of [Si(SiMe 2 OCH 2 CH 2 OMe) 4 ] ( 2 ) and [Ge(SiMe 2 OCH 2 CH 2 OMe) 4 ] ( 3 ) with MOBu t (M = Li, Na or K), resp., in almost quantitative yields, while M- 1 were prepared from deprotonation of [HC(SiMe 2 OCH 2 CH 2 OMe) 3 ] ( 1 ) with LiBu t , NaCH 2 Ph and KCH 2 Ph, resp. X-ray crystallographic studies and DFT calculations in the gas-phase, including calculations of the NPA charges confirm the zwitterionic nature of these compounds, with the alkali metal cations being rigidly locked and charge separated from the anion by the internal OCH 2 CH 2 OMe donor groups. Natural bond orbital (NBO) analysis and the second order perturbation theory analysis of the NBOs reveal significant hyperconjugative interactions in M- 1 -M- 3 , primarily between the lone pair and the antibonding Si-O orbitals, the extent of which decreases in the order M- 1 > M- 2 > M- 3 . The experimental basicities and the calculated gas-phase basicities of M- 1 -M- 3 reveal the zwitterionic alkali metal methanides M- 1 to be significantly stronger bases than the analogous silanides M- 2 and germanium M- 3 .

  14. Facile surface modification of silicone rubber with zwitterionic polymers for improving blood compatibility

    International Nuclear Information System (INIS)

    Liu, Pingsheng; Chen, Qiang; Yuan, Bo; Chen, Mengzhou; Wu, Shishan; Lin, Sicong; Shen, Jian

    2013-01-01

    A facile approach to modify silicone rubber (SR) membrane for improving the blood compatibility was investigated. The hydrophobic SR surface was firstly activated by air plasma, after which an initiator was immobilized on the activated surface for atom transfer radical polymerization (ATRP). Three zwitterionic polymers were then grafted from SR membrane via surface-initiated atom transfer radical polymerization (SI-ATRP). The surface composition, wettability, and morphology of the membranes before and after modification were characterized by X-ray photoelectron spectroscopy (XPS), static water contact angle (WCA) measurement, and atomic force microscopy (AFM). Results showed that zwitterionic polymers were successfully grafted from SR surfaces, which remarkably improved the wettability of the SR surface. The blood compatibility of the membranes was evaluated by protein adsorption and platelet adhesion tests in vitro. As observed, all the zwitterionic polymer modified surfaces have improved resistance to nonspecific protein adsorption and have excellent resistance to platelet adhesion, showing significantly improved blood compatibility. This work should inspire many creative uses of SR based materials for biomedical applications such as vessel, catheter, and microfluidics. Highlights: • Facile surface modification of silicone rubber with functional brushes • Modified SR surfaces have improved resistance to nonspecific protein adsorption. • Modified SR surfaces have excellent resistance to platelet adhesion. • Zwitteironic surface significant improvement in blood compatibility • Could inspire many creative uses of SR based materials for biomedical

  15. Facile surface modification of silicone rubber with zwitterionic polymers for improving blood compatibility

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Pingsheng [School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093 (China); Chen, Qiang, E-mail: chem100@nju.edu.cn [School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093 (China); High Technology Research Institute of Nanjing University, Changzhou 213164 (China); Yuan, Bo; Chen, Mengzhou; Wu, Shishan; Lin, Sicong [School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093 (China); Shen, Jian, E-mail: shenj1957@yahoo.com.cn [School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093 (China)

    2013-10-15

    A facile approach to modify silicone rubber (SR) membrane for improving the blood compatibility was investigated. The hydrophobic SR surface was firstly activated by air plasma, after which an initiator was immobilized on the activated surface for atom transfer radical polymerization (ATRP). Three zwitterionic polymers were then grafted from SR membrane via surface-initiated atom transfer radical polymerization (SI-ATRP). The surface composition, wettability, and morphology of the membranes before and after modification were characterized by X-ray photoelectron spectroscopy (XPS), static water contact angle (WCA) measurement, and atomic force microscopy (AFM). Results showed that zwitterionic polymers were successfully grafted from SR surfaces, which remarkably improved the wettability of the SR surface. The blood compatibility of the membranes was evaluated by protein adsorption and platelet adhesion tests in vitro. As observed, all the zwitterionic polymer modified surfaces have improved resistance to nonspecific protein adsorption and have excellent resistance to platelet adhesion, showing significantly improved blood compatibility. This work should inspire many creative uses of SR based materials for biomedical applications such as vessel, catheter, and microfluidics. Highlights: • Facile surface modification of silicone rubber with functional brushes • Modified SR surfaces have improved resistance to nonspecific protein adsorption. • Modified SR surfaces have excellent resistance to platelet adhesion. • Zwitteironic surface significant improvement in blood compatibility • Could inspire many creative uses of SR based materials for biomedical.

  16. Improved antifouling performance of ultrafiltration membrane via preparing novel zwitterionic polyimide

    Science.gov (United States)

    Huang, Haitao; Yu, Jiayu; Guo, Hanxiang; Shen, Yibo; Yang, Fan; Wang, Han; Liu, Rong; Liu, Yang

    2018-01-01

    On the basis of the outstanding fouling resistance of zwitterionic polymers, an antifouling ultrafiltration membrane was fabricated through phase inversion induced by immersion precipitation method, directly using the novel zwitterionic polyimide (Z-PI), which was synthesized via a two-step procedure including polycondensation and quaternary amination reaction, as membrane material. The chemical structure and composition of the obtained polymer were confirmed by using FTIR, 1H NMR and XPS analysis, and its thermal stability was thoroughly characterized by TGA measurement, respectively. The introduction of zwitterionic groups into polyimide could effectively increase membrane pore size, porosity and wettability, and convert the membrane surface from hydrophobic to highly hydrophilic. As a result, Z-PI membrane displayed significantly improved water permeability compared with that of the reference polyimide (R-PI) membrane without having an obvious compromise in protein rejection. According to the static adsorption and dynamic cycle ultrafiltration experiments of bovine serum albumin (BSA) solution, Z-PI membrane exhibited better fouling resistant ability, especially irreversible fouling resistant ability, suggesting superior antifouling property and long-term performance stability. Moreover, Z-PI membrane had a water flux recovery ratio of 93.7% after three cycle of BSA solution filtration, whereas only about 68.5% was obtained for the control R-PI membrane. These findings demonstrated the advantages of Z-PI membrane material and aimed to provide a facile and scalable method for the large-scale preparation of low fouling ultrafiltration membranes for potential applications.

  17. Surface modification of silicon wafer by grafting zwitterionic polymers to improve its antifouling property

    Science.gov (United States)

    Sun, Yunlong; Chen, Changlin; Xu, Heng; Lei, Kun; Xu, Guanzhe; Zhao, Li; Lang, Meidong

    2017-10-01

    Silicon (111) wafer was modified by triethoxyvinylsilane containing double bond as an intermedium, and then P4VP (polymer 4-vinyl pyridine) brush was "grafted" onto the surface of silicon wafer containing reactive double bonds by adopting the "grafting from" way and Si-P4VP substrate (silicon wafer grafted by P4VP) was obtained. Finally, P4VP brush of Si-P4VP substrate was modified by 1,3-propanesulfonate fully to obtain P4VP-psl brush (zwitterionic polypyridinium salt) and the functional Si-P4VP-psl substrate (silicon wafer grafted by zwitterionic polypyridinium salt based on polymer 4-vinyl pyridine) was obtained successfully. The antifouling property of the silicon wafer, the Si-P4VP substrate and the Si-P4VP-psl substrate was investigated by using bovine serum albumin, mononuclear macrophages (RAW 264.7) and Escherichia coli (E. coli) ATTC25922 as model bacterium. The results showed that compared with the blank sample-silicon wafer, the Si-P4VP-psl substrate had excellent anti-adhesion ability against bovine serum albumin, cells and bacterium, due to zwitterionic P4VP-psl brush (polymer 4-vinyl pyridine salt) having special functionality like antifouling ability on biomaterial field.

  18. Silica Nanoparticles Functionalized with Zwitterionic Sulfobetaine Siloxane for Application as a Versatile Antifouling Coating System.

    Science.gov (United States)

    Knowles, Brianna R; Wagner, Pawel; Maclaughlin, Shane; Higgins, Michael J; Molino, Paul J

    2017-06-07

    The growing need to develop surfaces able to effectively resist biological fouling has resulted in the widespread investigation of nanomaterials with potential antifouling properties. However, the preparation of effective antifouling coatings is limited by the availability of reactive surface functional groups and our ability to carefully control and organize chemistries at a materials' interface. Here, we present two methods of preparing hydrophilic low-fouling surface coatings through reaction of silica-nanoparticle suspensions and predeposited silica-nanoparticle films with zwitterionic sulfobetaine (SB). Silica-nanoparticle suspensions were functionalized with SB across three pH conditions and deposited as thin films via a simple spin-coating process to generate hydrophilic antifouling coatings. In addition, coatings of predeposited silica nanoparticles were surface functionalized via exposure to zwitterionic solutions. Quartz crystal microgravimetry with dissipation monitoring was employed as a high throughput technique for monitoring and optimizing reaction to the silica-nanoparticle surfaces. Functionalization of nanoparticle films was rapid and could be achieved over a wide pH range and at low zwitterion concentrations. All functionalized particle surfaces presented a high degree of wettability and resulted in large reductions in adsorption of bovine serum albumin protein. Particle coatings also showed a reduction in adhesion of fungal spores (Epicoccum nigrum) and bacteria (Escherichia coli) by up to 87 and 96%, respectively. These results indicate the potential for functionalized nanosilicas to be further developed as versatile fouling-resistant coatings for widespread coating applications.

  19. Bottom-up fabrication of zwitterionic polymer brushes on intraocular lens for improved biocompatibility

    Directory of Open Access Journals (Sweden)

    Han Y

    2016-12-01

    Full Text Available Yuemei Han,1,* Xu Xu,1,* Junmei Tang,1,* Chenghui Shen,2 Quankui Lin,1,2 Hao Chen1,2 1School of Ophthalmology & Optometry, Eye Hospital, Wenzhou Medical University, 2Wenzhou Institute of Biomaterials and Engineering, Chinese Academy of Sciences, Wenzhou, People’s Republic of China *These authors contributed equally to this work Abstract: Intraocular lens (IOL is an efficient implantable device commonly used for treating cataracts. However, bioadhesion of bacteria or residual lens epithelial cells on the IOL surface after surgery causes postoperative complications, such as endophthalmitis or posterior capsular opacification, and leads to loss of sight again. In the present study, zwitterionic polymer brushes were fabricated on the IOL surface via bottom-up grafting procedure. The attenuated total reflection-Fourier transform infrared and contact angle measurements indicated successful surface modification, as well as excellent hydrophilicity. The coating of hydrophilic zwitterionic polymer effectively decreased the bioadhesion of lens epithelial cells or bacteria. In vivo intraocular implantation results showed good in vivo biocompatibility of zwitterionic IOL and its effectiveness against postoperative complications. Keywords: RAFT, surface modification, endophthalmitis, PCO, in vivo

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

    Science.gov (United States)

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

    2017-05-04

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

  1. Enhanced solubility and targeted delivery of curcumin by lipopeptide micelles.

    Science.gov (United States)

    Liang, Ju; Wu, Wenlan; Lai, Danyu; Li, Junbo; Fang, Cailin

    2015-01-01

    A lipopeptide (LP)-containing KKGRGDS as the hydrophilic heads and lauric acid (C12) as the hydrophobic tails has been designed and prepared by standard solid-phase peptide synthesis technique. LP can self-assemble into spherical micelles with the size of ~30 nm in PBS (phosphate buffer saline) (pH 7.4). Curcumin-loaded LP micelles were prepared in order to increase the water solubility, sustain the releasing rate, and improve the tumor targeted delivery of curcumin. Water solubility, cytotoxicity, in vitro release behavior, and intracellular uptake of curcumin-loaded LP micelles were investigated. The results showed that LP micelles can increase the water solubility of curcumin 1.1 × 10(3) times and sustain the release of curcumin in a low rate. Curcumin-loaded LP micelles showed much higher cell inhibition than free curcumin on human cervix carcinoma (HeLa) and HepG2 cells. When incubating these curcumin-loaded micelles with HeLa and COS7 cells, due to the over-expression of integrins on cancer cells, the micelles can efficiently use the tumor-targeting function of RGD (functionalized peptide sequences: Arg-Gly-Asp) sequence to deliver the drug into HeLa cells, and better efficiency of the self-assembled LP micelles for curcumin delivery than crude curcumin was also confirmed by LCSM (laser confocal scanning microscope) assays. Combined with the enhanced solubility and higher cell inhibition, LP micelles reported in this study may be promising in clinical application for targeted curcumin delivery.

  2. 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.

  3. Reverse micelles as a tool for probing solvent modulation of protein dynamics: Reverse micelle encapsulated hemoglobin

    Science.gov (United States)

    Roche, Camille J.; Dantsker, David; Heller, Elizabeth R.; Sabat, Joseph E.; Friedman, Joel M.

    2013-08-01

    Hydration waters impact protein dynamics. Dissecting the interplay between hydration waters and dynamics requires a protein that manifests a broad range of dynamics. Proteins in reverse micelles (RMs) have promise as tools to achieve this objective because the water content can be manipulated. Hemoglobin is an appropriate tool with which to probe hydration effects. We describe both a protocol for hemoglobin encapsulation in reverse micelles and a facile method using PEG and cosolvents to manipulate water content. Hydration properties are probed using the water-sensitive fluorescence from Hb bound pyranine and covalently attached Badan. Protein dynamics are probed through ligand recombination traces derived from photodissociated carbonmonoxy hemoglobin on a log scale that exposes the potential role of both α and β solvent fluctuations in modulating protein dynamics. The results open the possibility of probing hydration level phenomena in this system using a combination of NMR and optical probes.

  4. 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.

  5. Depletion interaction of casein micelles and an exocellular polysaccharide

    Science.gov (United States)

    Tuinier, R.; Ten Grotenhuis, E.; Holt, C.; Timmins, P. A.; de Kruif, C. G.

    1999-07-01

    Casein micelles become mutually attractive when an exocellular polysaccharide produced by Lactococcus lactis subsp. cremoris NIZO B40 (hereafter called EPS) is added to skim milk. The attraction can be explained as a depletion interaction between the casein micelles induced by the nonadsorbing EPS. We used three scattering techniques (small-angle neutron scattering, turbidity measurements, and dynamic light scattering) to measure the attraction. In order to connect the theory of depletion interaction with experiment, we calculated structure factors of hard spheres interacting by a depletion pair potential. Theoretical predictions and all the experiments showed that casein micelles became more attractive upon increasing the EPS concentration.

  6. 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.

  7. 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

  8. Logarithmic Exchange Kinetics in Monodisperse Copolymeric Micelles

    Science.gov (United States)

    García Daza, Fabián A.; Bonet Avalos, Josep; Mackie, Allan D.

    2017-06-01

    Experimental measurements of the relaxation kinetics of copolymeric surfactant exchange for micellar systems unexpectedly show a peculiar logarithmic decay. Several authors use polydispersity as an explanation for this behavior. However, in coarse-grained simulations that preserve microscopic details of the surfactants, we find evidence of the same logarithmic behavior. Since we use a strictly monodisperse distribution of chain lengths such a relaxation process cannot be attributed to polydispersity, but has to be caused by an inherent physical process characteristic of this type of system. This is supported by the fact that the decay is specifically logarithmic and not a power law with an exponent inherited from the particular polydispersity distribution of the sample. We suggest that the degeneracy of the energy states of the hydrophobic block in the core, which is broken on leaving the micelle, can qualitatively explain the broad distribution of energy barriers, which gives rise to the observed nonexponential relaxation.

  9. The relative abundance of dimethylsulfoniopropionate (DMSP) among other zwitterions in branching coral at Heron Island, southern Great Barrier Reef.

    Science.gov (United States)

    Swan, Hilton B; Deschaseaux, Elisabeth S M; Jones, Graham B; Eyre, Bradley D

    2017-07-01

    Dimethylsulfoniopropionate (DMSP) and eleven other target zwitterions were quantified in the branch tips of six Acropora species and Stylophora pistillata hard coral growing on the reef flat surrounding Heron Island in the southern Great Barrier Reef (GBR), Australia. Hydrophilic interaction liquid chromatography mass spectrometry (HILIC-MS) was used for sample analysis with isotope dilution MS applied to quantify DMSP. The concentration of DMSP was ten times greater in A. aspera than A. valida, with this difference being maintained throughout the spring, summer and winter seasons. In contrast, glycine betaine was present in significantly higher concentrations in these species during the summer than the winter. Exposure of branch tips of A. aspera to air and hypo-saline seawater for up to 1 h did not alter the concentrations of DMSP present in the coral when compared with control samples. DMSP was the most abundant target zwitterion in the six Acropora species examined, ranging from 44-78% of all target zwitterions in A. millepora and A. aspera, respectively. In contrast, DMSP only accounted for 7% in S. pistillata, with glycine betaine and stachydrine collectively accounting for 88% of all target zwitterions in this species. The abundance of DMSP in the six Acropora species examined points to Acropora coral being an important source for the biogeochemical cycling of sulfur throughout the GBR, since this reef-building branching coral dominates the coral cover of the GBR. Graphical Abstract HILIC-MS extracted ion chromatogram showing zwitterionic metabolites from the branching coral Acropora isopora.

  10. Synergistic effects on enantioselectivity of zwitterionic chiral stationary phases for separations of chiral acids, bases, and amino acids by HPLC.

    Science.gov (United States)

    Hoffmann, Christian V; Pell, Reinhard; Lämmerhofer, Michael; Lindner, Wolfgang

    2008-11-15

    In an attempt to overcome the limited applicability scope of earlier proposed Cinchona alkaloid-based chiral weak anion exchangers (WAX) and recently reported aminosulfonic acid-based chiral strong cation exchangers (SCX), which are conceptionally restricted to oppositely charged solutes, their individual chiral selector (SO) subunits have been fused in a combinatorial synthesis approach into single, now zwitterionic, chiral SO motifs. The corresponding zwitterionic ion-exchange-type chiral stationary phases (CSPs) in fact combined the applicability spectra of the parent chiral ion exchangers allowing for enantioseparations of chiral acids and amine-type solutes in liquid chromatography using polar organic mode with largely rivaling separation factors as compared to the parent WAX and SCX CSPs. Furthermore, the application spectrum could be remarkably expanded to various zwitterionic analytes such as alpha- and beta-amino acids and peptides. A set of structurally related yet different CSPs consisting of either a quinine or quinidine alkaloid moiety as anion-exchange subunit and various chiral or achiral amino acids as cation-exchange subunits enabled us to derive structure-enantioselectivity relationships, which clearly provided strong unequivocal evidence for synergistic effects of the two oppositely charged ion-exchange subunits being involved in molecular recognition of zwitterionic analytes by zwitterionic SOs driven by double ionic coordination.

  11. Structure and reactivity in amphiphile-water micelles

    International Nuclear Information System (INIS)

    Chevalier, Yves

    1985-01-01

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

  12. Influence of succinylation on physicochemical property of yak casein micelles.

    Science.gov (United States)

    Yang, Min; Yang, Jitao; Zhang, Yuan; Zhang, Weibing

    2016-01-01

    Succinylation is a chemical-modification method that affects the physicochemical characteristics and functional properties of proteins. This study assessed the influence of succinylation on the physicochemical properties of yak casein micelles. The results revealed that surface hydrophobicity indices decreased with succinylation. Additionally, denaturation temperature and denaturation enthalpy decreased with increasing succinylation level, except at 82%. The buffering properties of yak casein micelles were affected by succinylation. It was found that chemical modification contributed to a slight shift of the buffering peak towards a lower pH value and a markedly increase of the maximum buffering values of yak casein micelles at pH 4.5-6.0 and pH casein micellar hydration and whiteness values. The findings obtained from this study will provide the basic information on the physicochemical properties of native and succinylated yak casein micelles. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Interactions of casein micelles with calcium phosphate particles.

    Science.gov (United States)

    Tercinier, Lucile; Ye, Aiqian; Anema, Skelte G; Singh, Anne; Singh, Harjinder

    2014-06-25

    Insoluble calcium phosphate particles, such as hydroxyapatite (HA), are often used in calcium-fortified milks as they are considered to be chemically unreactive. However, this study showed that there was an interaction between the casein micelles in milk and HA particles. The caseins in milk were shown to bind to the HA particles, with the relative proportions of bound β-casein, αS-casein, and κ-casein different from the proportions of the individual caseins present in milk. Transmission electron microscopy showed no evidence of intact casein micelles on the surface of the HA particles, which suggested that the casein micelles dissociated either before or during binding. The HA particles behaved as ion chelators, with the ability to bind the ions contained in the milk serum phase. Consequently, the depletion of the serum minerals disrupted the milk mineral equilibrium, resulting in dissociation of the casein micelles in milk.

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

    KAUST Repository

    Deng, Lin; Wang, Guangchao; Ren, Jian; Zhang, Bei; Yan, Jingjing; Li, Wengang; Khashab, Niveen M.

    2012-01-01

    (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.

  15. Synthesis and immobilization of polystyreneb-polyvinyltriethoxysilane micelles

    KAUST Repository

    Zhu, Saisai; Zhu, Hui; Xia, Ru; Feng, Xiaoshuang; Chen, Peng; Qian, Jiasheng; Cao, Ming; Yang, Bin; Miao, Jibin; Su, Lifen; Song, Changjiang

    2018-01-01

    Diblock copolymers polystyrene-block-polyvinyltriethoxysilane (PS-b-PVTES) were synthesized via atom transfer radical polymerization (ATRP), which self-assembled into spherical micelles in solvent of THF-methanol mixtures. The self

  16. A neutron scattering study of triblock copolymer micelles

    Energy Technology Data Exchange (ETDEWEB)

    Gerstenberg, M.C.

    1997-11-01

    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

  17. Polymeric micelles for potentiated antiulcer and anticancer activities of naringin

    Science.gov (United States)

    Mohamed, Elham Abdelmonem; Abu Hashim, Irhan Ibrahim; Yusif, Rehab Mohammad; Shaaban, Ahmed Abdel Aziz; El-Sheakh, Ahmed Ramadan; Hamed, Mohammed Fawzy; Badria, Farid Abd Elreheem

    2018-01-01

    Naringin is one of the most interesting phytopharmaceuticals that has been widely investigated for various biological actions. Yet, its low water solubility, limited permeability, and suboptimal bioavailability limited its use. Therefore, in this study, polymeric micelles of naringin based on pluronic F68 (PF68) were developed, fully characterized, and optimized. The optimized formula was investigated regarding in vitro release, storage stability, and in vitro cytotoxicity vs different cell lines. Also, cytoprotection against ethanol-induced ulcer in rats and antitumor activity against Ehrlich ascites carcinoma in mice were investigated. Nanoscopic and nearly spherical 1:50 micelles with the mean diameter of 74.80±6.56 nm and narrow size distribution were obtained. These micelles showed the highest entrapment efficiency (EE%; 96.14±2.29). The micelles exhibited prolonged release up to 48 vs 10 h for free naringin. The stability of micelles was confirmed by insignificant changes in drug entrapment, particle size, and retention (%) (91.99±3.24). At lower dose than free naringin, effective cytoprotection of 1:50 micelles against ethanol-induced ulcer in rat model has been indicated by significant reduction in mucosal damage, gastric level of malondialdehyde, gastric expression of tumor necrosis factor-alpha, caspase-3, nuclear factor kappa-light-chain-enhancer of activated B cells, and interleukin-6 with the elevation of gastric reduced glutathione and superoxide dismutase when compared with the positive control group. As well, these micelles provoked pronounced antitumor activity assessed by potentiated in vitro cytotoxicity particularly against colorectal carcinoma cells and tumor growth inhibition when compared with free naringin. In conclusion, 1:50 naringin–PF68 micelles can be represented as a potential stable nanodrug delivery system with prolonged release and enhanced antiulcer as well as antitumor activities. PMID:29497294

  18. 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

  19. Nanoscale elastic modulus variation in loaded polymeric micelle reactors.

    Science.gov (United States)

    Solmaz, Alim; Aytun, Taner; Deuschle, Julia K; Ow-Yang, Cleva W

    2012-07-17

    Tapping mode atomic force microscopy (TM-AFM) enables mapping of chemical composition at the nanoscale by taking advantage of the variation in phase angle shift arising from an embedded second phase. We demonstrate that phase contrast can be attributed to the variation in elastic modulus during the imaging of zinc acetate (ZnAc)-loaded reverse polystyrene-block-poly(2-vinylpyridine) (PS-b-P2VP) diblock co-polymer micelles less than 100 nm in diameter. Three sample configurations were characterized: (i) a 31.6 μm thick polystyrene (PS) support film for eliminating the substrate contribution, (ii) an unfilled PS-b-P2VP micelle supported by the same PS film, and (iii) a ZnAc-loaded PS-b-P2VP micelle supported by the same PS film. Force-indentation (F-I) curves were measured over unloaded micelles on the PS film and over loaded micelles on the PS film, using standard tapping mode probes of three different spring constants, the same cantilevers used for imaging of the samples before and after loading. For calibration of the tip geometry, nanoindentation was performed on the bare PS film. The resulting elastic modulus values extracted by applying the Hertz model were 8.26 ± 3.43 GPa over the loaded micelles and 4.17 ± 1.65 GPa over the unloaded micelles, confirming that phase contrast images of a monolayer of loaded micelles represent maps of the nanoscale chemical and mechanical variation. By calibrating the tip geometry indirectly using a known soft material, we are able to use the same standard tapping mode cantilevers for both imaging and indentation.

  20. A neutron scattering study of triblock copolymer micelles

    International Nuclear Information System (INIS)

    Gerstenberg, M.C.

    1997-11-01

    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. Kinetics of CO2 with primary and secondary amines in aqueous solutions I. Zwitterion deprotonation kinetics for DEA and DIPA in aqueous blends of alkanolamines

    NARCIS (Netherlands)

    Littel, R.J.; Littel, R.J.; Versteeg, Geert; van Swaaij, Willibrordus Petrus Maria

    1992-01-01

    The deprotonation kinetics of the DEA—CO2 and the DIPA—CO2 zwitterions have been studied in aqueous blends of amines at 298 K. Amine mixtures investigated were: DEA—TEA, DEA—MDEA, DEA—DMMEA, DEA—DEMEA, DIPA—TEA. DIPA—MDEA, DIPA—DMMEA, DIPA—DEMEA. For each blend the zwitterion deprotonation constant

  2. Kinetics of CO2 with primary and secondary amines in aqueous solutions—I. Zwitterion deprotonation kinetics for DEA and DIPA in aqueous blends of alkanolamines

    NARCIS (Netherlands)

    Littel, R.J.; Versteeg, G.F.; Swaaij, W.P.M. van

    1992-01-01

    The deprotonation kinetics of the DEA—CO2 and the DIPA—CO2 zwitterions have been studied in aqueous blends of amines at 298 K. Amine mixtures investigated were: DEA—TEA, DEA—MDEA, DEA—DMMEA, DEA—DEMEA, DIPA—TEA. DIPA—MDEA, DIPA—DMMEA, DIPA—DEMEA. For each blend the zwitterion deprotonation constant

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

    KAUST Repository

    Shi, Yifeng; Li, Bin; Wang, Peng; Dua, Rubal; Zhao, Dongyuan

    2012-01-01

    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

  4. The pH behavior of a 2-aminoethyl dihydrogen phosphate zwitterion studied with NMR-titrations

    Science.gov (United States)

    Myller, A. T.; Karhe, J. J.; Haukka, M.; Pakkanen, T. T.

    2013-02-01

    In this study a bifunctional 2-aminoethyl dihydrogen phosphate (AEPH2) was 1H and 31P NMR characterized in a pH range of 1-12 in order to determine the zwitterion properties in different pH regions in H2O and D2O solutions. NMR was also used to determine the pH range where AEPH2 exists as a zwitterion. The phosphate group has two deprotonation points, around pH 1 and 6, while the amino group deprotonates at pH 11. The zwitterion form of AEPH2 (NH3+sbnd CHsbnd CHsbnd OPOH) exists as the main ion between pH 1 and 6 in water solutions and also in the solid state.

  5. Zwitterionic sulfobetaine polymer-immobilized surface by simple tyrosinase-mediated grafting for enhanced antifouling property.

    Science.gov (United States)

    Kwon, Ho Joon; Lee, Yunki; Phuong, Le Thi; Seon, Gyeung Mi; Kim, Eunsuk; Park, Jong Chul; Yoon, Hyunjin; Park, Ki Dong

    2017-10-01

    Introducing antifouling property to biomaterial surfaces has been considered an effective method for preventing the failure of implanted devices. In order to achieve this, the immobilization of zwitterions on biomaterial surfaces has been proven to be an excellent way of improving anti-adhesive potency. In this study, poly(sulfobetaine-co-tyramine), a tyramine-conjugated sulfobetaine polymer, was synthesized and simply grafted onto the surface of polyurethane via a tyrosinase-mediated reaction. Surface characterization by water contact angle measurements, X-ray photoelectron spectroscopy and atomic force microscopy demonstrated that the zwitterionic polymer was successfully introduced onto the surface of polyurethane and remained stable for 7days. In vitro studies revealed that poly(sulfobetaine-co-tyramine)-coated surfaces dramatically reduced the adhesion of fibrinogen, platelets, fibroblasts, and S. aureus by over 90% in comparison with bare surfaces. These results proved that polyurethane surfaces grafted with poly(sulfobetaine-co-tyramine) via a tyrosinase-catalyzed reaction could be promising candidates for an implantable medical device with excellent bioinert abilities. Antifouling surface modification is one of the key strategy to prevent the thrombus formation or infection which occurs on the surface of biomaterial after transplantation. Although there are many methods to modify the surface have been reported, necessity of simple modification technique still exists to apply for practical applications. The purpose of this study is to modify the biomaterial's surface by simply immobilizing antifouling zwitterion polymer via enzyme tyrosinase-mediated reaction which could modify versatile substrates in mild aqueous condition within fast time period. After modification, pSBTA grafted surface becomes resistant to various biological factors including proteins, cells, and bacterias. This approach appears to be a promising method to impart antifouling property on

  6. Modelling zwitterions in solution: 3-fluoro-γ-aminobutyric acid (3F-GABA).

    Science.gov (United States)

    Cao, Jie; Bjornsson, Ragnar; Bühl, Michael; Thiel, Walter; van Mourik, Tanja

    2012-01-02

    The conformations and relative stabilities of folded and extended 3-fluoro-γ-aminobutyric acid (3F-GABA) conformers were studied using explicit solvation models. Geometry optimisations in the gas phase with one or two explicit water molecules favour folded and neutral structures containing intramolecular NH···O-C hydrogen bonds. With three or five explicit water molecules zwitterionic minima are obtained, with folded structures being preferred over extended conformers. The stability of folded versus extended zwitterionic conformers increases on going from a PCM continuum solvation model to the microsolvated complexes, though extended structures become less disfavoured with the inclusion of more water molecules. Full explicit solvation was studied with a hybrid quantum-mechanical/molecular-mechanical (QM/MM) scheme and molecular dynamics simulations, including more than 6000 TIP3P water molecules. According to free energies obtained from thermodynamic integration at the PM3/MM level and corrected for B3LYP/MM total energies, the fully extended conformer is more stable than folded ones by about -4.5 kJ mol(-1). B3LYP-computed (3)J(F,H) NMR spin-spin coupling constants, averaged over PM3/MM-MD trajectories, agree best with experiment for this fully extended form, in accordance with the original NMR analysis. The seeming discrepancy between static PCM calculations and experiment noted previously is now resolved. That the inexpensive semiempirical PM3 method performs so well for this archetypical zwitterion is encouraging for further QM/MM studies of biomolecular systems. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Proton transport properties in zwitterion blends with Brønsted acids.

    Science.gov (United States)

    Yoshizawa-Fujita, Masahiro; Byrne, Nolene; Forsyth, Maria; MacFarlane, Douglas R; Ohno, Hiroyuki

    2010-12-16

    We describe zwitterion, 3-(1-butyl-1H-imidazol-3-ium-3-yl)propane-1-sulfonate (Bimps), mixtures with 1,1,1-trifluoro-N-(trifluoromethylsulfonyl)methanesulfoneamide (HN(Tf)(2)) as new proton transport electrolytes. We report proton transport mechanisms in the mixtures based on results from several methods including thermal analyses, the complex-impedance method, and the pulsed field gradient spin echo NMR (pfg-NMR) method. The glass transition temperature (Tg) of the mixtures decreased with increasing HN(Tf)(2) concentration up to 50 mol %. The Tg remained constant at -55 °C with further acid doping. The ionic conductivity of HN(Tf)(2) mixtures increased with the HN(Tf)(2) content up to 50 mol %. Beyond that ratio, the mixtures showed no increase in ionic conductivity (10(-4) S cm(-1) at room temperature). This tendency agrees well with that of Tg. However, the self-diffusion coefficients obtained from the pfg-NMR method increased with HN(Tf)(2) content even above 50 mol % for all component ions. At HN(Tf)(2) 50 mol %, the proton diffusion of HN(Tf)(2) was the fastest in the mixture. These results suggest that Bimps cannot dissociate excess HN(Tf)(2), that is, the excess HN(Tf)(2) exists as molecular HN(Tf)(2) in the mixtures. The zwitterion, Bimps, forms a 1:1 complex with HN(Tf)(2) and the proton transport property in this mixture is superior to those of other mixing ratios. Furthermore, CH(3)SO(3)H and CF(3)SO(3)H were mixed with Bimps for comparison. Both systems showed a similar tendency, which differed from that of the HN(Tf)(2) system. The Tg decreased linearly with increasing acid content for every mixing ratio, while the ionic conductivity increased linearly. Proton transport properties in zwitterion/acid mixtures were strongly affected by the acid species added.

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

    International Nuclear Information System (INIS)

    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. The structure and interactions of the micelles were modeled in detail. The convolution of the center distribution of the micelles, obtained from Monte Carlo simulations of hard spheres at a hard wall, and the projected density of the micelle showed excellent agreement with the experimental profiles. copyright 1998 The American Physical Society

  9. 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....... The structure and interactions of the micelles were modeled in detail. The convolution of the center distribution of the micelles, obtained from Monte Carlo simulations of hard spheres at a hard wall, and the projected density of the micelle showed excellent agreement with the experimental profiles. [S1063-651X...

  10. Dye sensitized photovoltaic cells: Attaching conjugated polymers to zwitterionic ruthenium dyes

    DEFF Research Database (Denmark)

    Krebs, Frederik C; Biancardo, M.

    2006-01-01

    The synthesis of a zwitterionic ruthenium dye that binds to anatase surfaces and has a built-in functionality that allows for the attachment of a conjugated polymer chain is presented. The system was found to adsorb on the surface of anatase anchored by the ruthenium dye. Two types of devices were...... prepared: standard photoelectrochemical (PEC) solar cells and polymer solar cells. The PEC solar cells employed a sandwich geometry between TiO2 nanoporous photoanodes and Pt counter electrodes using LiI/I-2 in CH3CN as an electrolyte. The polymer solar cells employed planar anatase electrodes...

  11. Isolation of a Moderately Stable but Sensitive Zwitterionic Diazonium Tetrazolyl-1,2,3-triazolate.

    Science.gov (United States)

    Klapötke, Thomas M; Krumm, Burkhard; Pflüger, Carolin

    2016-07-15

    An unexpected formation of a diazonium compound was observed by nitration of an amino substituted triazolyl tetrazole with mixed acid. The crystal structure determination revealed a zwitterionic diazonium tetrazolyl-1,2,3-triazolate, whose constitution was supported by NMR and vibrational spectroscopic analysis. The thermal stability and sensitivity toward impact and friction were determined. In contrast, diazotriazoles are rather unstable and are mainly handled in solution and/or low temperatures, which is not the case for this diazonium tetrazolyl-1,2,3-triazolate, being stable at ambient temperature.

  12. Zwitterionic bis(phenolate)amine lanthanide complexes for the ring-opening polymerisation of cyclic esters

    NARCIS (Netherlands)

    Dyer, H.E.; Huijser, S.; Schwarz, A.D.; Wang, Chao; Duchateau, R.; Mountford, P.

    2008-01-01

    The reaction of Sm{N(SiMe3)2}3 with the bis(phenol)amines H2O2NR (H2O 2NR = RCH2CH2N(2-HO-3,5-C 6H2tBu2)2; R = OMe, NMe2 or Me) gave exclusively zwitterions Sm(O2N R)(HO2NR). For R = OMe or NMe2 these were efficient catalysts for the ring-opening polymerisation of e-caprolactone and d,l-lactide with

  13. Palladium catalyst system comprising zwitterion and/or acid-​functionalized ionic liquid

    DEFF Research Database (Denmark)

    2011-01-01

    The present invention concerns a catalyst system in particular a catalyst system comprising Palladium (Pd), a zwitterion and/or an acid-functionalized ionic liquid, and one or more phosphine ligands, wherein the Pd catalyst can be provided by a complex precursor, such as Pd(CH3COO)2, PdCI2, Pd(CH3...... methyl methacrylate and/or methacrylic acid. Catalyst systems according to the invention are suitable for reactions forming separable product and catalyst phases and supported ionic liquid phase SILP applications....

  14. New chiral zwitterionic phosphorus heterocycles: synthesis, structure, properties and application as chiral solvating agents.

    Science.gov (United States)

    Sheshenev, Andrey E; Boltukhina, Ekaterina V; Grishina, Anastasiya A; Cisařova, Ivana; Lyapkalo, Ilya M; Hii, King Kuok Mimi

    2013-06-17

    A family of new chiral zwitterionic phosphorus-containing heterocycles (zPHC) have been derived from methylene-bridged bis(imidazolines). These structures were unambiguously determined, including single-crystal XRD analysis for two compounds. The stability, acid/base and electronic properties of these dipolar phosphorus heterocycles were subsequently investigated. zPHCs can be successfully employed as a new class of chiral solvating agents for the enantiodifferentiation of chiral carboxylic and sulfonic acids by NMR spectroscopy. The stoichiometry and binding constants for the donor-acceptor complexes formed were established by NMR titration methods. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Quantitative fabrication, performance optimization and comparison of PEG and zwitterionic polymer antifouling coatings.

    Science.gov (United States)

    Xing, Cheng-Mei; Meng, Fan-Ning; Quan, Miao; Ding, Kai; Dang, Yuan; Gong, Yong-Kuan

    2017-09-01

    A versatile fabrication and performance optimization strategy of PEG and zwitterionic polymer coatings is developed on the sensor chip of surface plasma resonance (SPR) instrument. A random copolymer bearing phosphorylcholine zwitterion and active ester side chains (PMEN) and carboxylic PEG coatings with comparable thicknesses were deposited on SPR sensor chips via amidation coupling on the precoated polydopamine (PDA) intermediate layer. The PMEN coating showed much stronger resistance to bovine serum albumin (BSA) adsorption than PEG coating at very thin thickness (∼1nm). However, the BSA resistant efficacy of PEG coating could exceed that of PMEN due to stronger steric repelling effect when the thickness increased to 1.5∼3.3nm. Interestingly, both the PEG and PMEN thick coatings (≈3.6nm) showed ultralow fouling by BSA and bovine plasma fibrinogen (Fg). Moreover, changes in the PEG end group from -OH to -COOH, protein adsorption amount could increase by 10-fold. Importantly, the optimized PMEN and PEG-OH coatings were easily duplicated on other substrates due to universal adhesion of the PDA layer, showed excellent resistance to platelet, bacteria and proteins, and no significant difference in the antifouling performances was observed. These detailed results can explain the reported discrepancy in performances between PEG and zwitterionic polymer coatings by thickness. This facile and substrate-independent coating strategy may benefit the design and manufacture of advanced antifouling biomedical devices and long circulating nanocarriers. Prevention of biofouling is one of the biggest challenges for all biomedical applications. However, it is very difficult to fabricate a highly hydrophilic antifouling coating on inert materials or large devices. In this study, PEG and zwitterion polymers, the most widely investigated polymers with best antifouling performance, are conveniently immobilized on different kinds of substrates from their aqueous solutions by

  16. Synthesis of zwitterionic salts of pyridinium-Meldrum acid and barbiturate through unique four-component reactions.

    Science.gov (United States)

    Wang, Qi-Fang; Hui, Li; Hou, Hong; Yan, Chao-Guo

    2010-03-08

    An efficient synthetic procedure for the preparation of the unusual charge-separated pyridinium-Meldrum acid and N,N-dimethylbarbiturate acid zwitterionic salts was developed though a unique one-pot four-component reaction involving pyridine, aromatic aldehyde, Meldrum acid or N,N-dimethylbarbituric acid, and p-nitrobenzyl bromide in acetonitrile. By varying combinations of four components involving nitrogen-containing heterocycles, we conveniently established reactive alpha-halomethylene compounds, aldehydes and beta-dicarbonyl compounds a library of zwitterionic salts.

  17. On the freezing behavior and diffusion of water in proximity to single-supported zwitterionic and anionic bilayer lipid membranes

    DEFF Research Database (Denmark)

    Miskowiec, A.; Buck, Z. N.; Brown, M. C.

    2014-01-01

    We compare the freezing/melting behavior of water hydrating single-supported bilayers of a zwitterionic lipid DMPC with that of an anionic lipid DMPG. For both membranes, the temperature dependence of the elastically scattered neutron intensity indicates distinct water types undergoing...... translational diffusion: bulk-like water probably located above the membrane and two types of confined water closer to the lipid head groups. The membranes differ in the greater width of the water freezing transition near the anionic DMPG bilayer compared to zwitterionic DMPC as well as in the abruptness...

  18. Amphipathic dextran-doxorubicin prodrug micelles for solid tumor therapy.

    Science.gov (United States)

    Jin, Rong; Guo, Xuelian; Dong, Lingli; Xie, Enyuan; Cao, Aoneng

    2017-10-01

    A group of micelles self-assembled from deoxycholic acid-doxorubicin-conjugated dextran (denoted as Dex-DCA-DOX) prodrugs were designed and prepared for pH-triggered drug release and cancer chemotherapy. These prodrugs could be successfully produced by chemically coupling hydrophobic deoxycholic acid (DCA) to dextran hydrazine (denoted as Dex-NHNH 2 ) and hydrazone linker formation between doxorubicin (DOX) and Dex-NHNH 2 . These Dex-DCA-DOX prodrugs self-assembled to form micelles under physiological conditions with varied particle sizes depending on molecular weight of dextran, degree of substitution (DS) of DCA and DOX. After optimization, Dex10k-DCA9-DOX5.5 conjugate comprising dextran of 10kDa, DCA of DS 9 and DOX loading content of 5.5wt%, formed the micelles with the smallest size (110nm). These prodrug micelles could slowly liberate DOX under physiological conditions but efficiently released the drug at an acidified endosomal pH by the hydrolysis of acid-labile hydrazone linker. In vitro cytotoxicity experiment indicated that Dex10k-DCA9-DOX5.5 micelles exerted marked antitumor activity against MCF-7 and SKOV-3 cancer cells. Besides, intravenous administration of the micelles afforded growth inhibition of SKOV-3 tumor bearing in nude mice at a dosage of 2.5mg per kg with anti-cancer efficacy comparable to free DOX-chemotherapy but low systemic toxicity. This study highlights the feasibility of bio-safe and efficient dextran-based prodrug micelles designed for cancer chemotherapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. 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.

  20. Basic investigations on LCV micelle gel

    International Nuclear Information System (INIS)

    Ebenezer, S B; Rafic, M K; Ravindran, P B

    2013-01-01

    The aim of this study was to investigate the feasibility of using Leuco Crystal Violet (LCV) based micelle gel dosimeter as a quality assurance tool in radiotherapy applications. Basic properties such as absorption coefficient and diffusion of LCV gel phantom over time were evaluated. The gel formulation consisted of 25 mM Trichloroacetic acid, 1mM LCV, 4 mM Triton X-100, 4% gelatin by mass and distilled water. The advantages of using this gel are its tissue equivalence, easy and less preparation time, lower diffusion rate and it can be read with an optical scanner. We were able to reproduce some of the results of Babic et al. The peak absorption was found to be at 600 nm and hence a matrix of yellow LEDs was used as light source. The profiles obtained from projection images confirmed the diffusion of LCV gel after 6 hours of irradiation. Hence the LCV gel phantom should be read before 6 hours post irradiation to get accurate dose information as suggested previously.

  1. Synchronized Regulation of Different Zwitterionic Metabolites in the Osmoadaption of Phytoplankton

    Directory of Open Access Journals (Sweden)

    Georg Pohnert

    2013-06-01

    Full Text Available The ability to adapt to different seawater salinities is essential for cosmopolitan marine phytoplankton living in very diverse habitats. In this study, we examined the role of small zwitterionic metabolites in the osmoadaption of two common microalgae species Emiliania huxleyi and Prorocentrum minimum. By cultivation of the algae under salinities between 16‰ and 38‰ and subsequent analysis of dimethylsulfoniopropionate (DMSP, glycine betaine (GBT, gonyol, homarine, trigonelline, dimethylsulfonioacetate, trimethylammonium propionate, and trimethylammonium butyrate using HPLC-MS, we could reveal two fundamentally different osmoadaption mechanisms. While E. huxleyi responded with cell size reduction and a nearly constant ratio between the major metabolites DMSP, GBT and homarine to increasing salinity, osmolyte composition of P. minimum changed dramatically. In this alga DMSP concentration remained nearly constant at 18.6 mM between 20‰ and 32‰ but the amount of GBT and dimethylsulfonioacetate increased from 4% to 30% of total investigated osmolytes. Direct quantification of zwitterionic metabolites via LC-MS is a powerful tool to unravel the complex osmoadaption and regulation mechanisms of marine phytoplankton.

  2. On the structure and dynamics of water associated with single-supported zwitterionic and anionic membranes

    DEFF Research Database (Denmark)

    Miskowiec, A.; Buck, Z. N.; Hansen, Flemming Yssing

    2017-01-01

    We have used high-resolution quasielastic neutron scattering (QENS) to investigate the dynamics of water molecules (time scale of motion similar to ∼10-11- 10-9 s) in proximity to single-supported bilayers of the zwitterionic lipid DMPC (1,2-dimyristoyl-sn-glycero-3-phosphorylcholine) and the ani......We have used high-resolution quasielastic neutron scattering (QENS) to investigate the dynamics of water molecules (time scale of motion similar to ∼10-11- 10-9 s) in proximity to single-supported bilayers of the zwitterionic lipid DMPC (1,2-dimyristoyl-sn-glycero-3-phosphorylcholine......) and the anionic lipid DMPG (1,2-dimyristoyl-sn-glycero-3-phosphoglycerol) in the temperature range 160-295 K. For both membranes, the temperature dependence of the intensity of neutrons scattered elastically and incoherently from these samples indicates a series of freezing/melting transitions...... the membrane and two types of confined water in closer proximity to the lipids. Specifically, we propose a water type termed "confined 2" located within and just above the lipid head groups of the membrane and confined 1 water that lies between the bulk-like and confined 2 water. Confined 1 water is only...

  3. Highly Specific Binding on Antifouling Zwitterionic Polymer-Coated Microbeads as Measured by Flow Cytometry.

    Science.gov (United States)

    van Andel, Esther; de Bus, Ian; Tijhaar, Edwin J; Smulders, Maarten M J; Savelkoul, Huub F J; Zuilhof, Han

    2017-11-08

    Micron- and nano-sized particles are extensively used in various biomedical applications. However, their performance is often drastically hampered by the nonspecific adsorption of biomolecules, a process called biofouling, which can cause false-positive and false-negative outcomes in diagnostic tests. Although antifouling coatings have been extensively studied on flat surfaces, their use on micro- and nanoparticles remains largely unexplored, despite the widespread experimental (specifically, clinical) uncertainties that arise because of biofouling. Here, we describe the preparation of magnetic micron-sized beads coated with zwitterionic sulfobetaine polymer brushes that display strong antifouling characteristics. These coated beads can then be equipped with recognition elements of choice, to enable the specific binding of target molecules. First, we present a proof of principle with biotin-functionalized beads that are able to specifically bind fluorescently labeled streptavidin from a complex mixture of serum proteins. Moreover, we show the versatility of the method by demonstrating that it is also possible to functionalize the beads with mannose moieties to specifically bind the carbohydrate-binding protein concanavalin A. Flow cytometry was used to show that thus-modified beads only bind specifically targeted proteins, with minimal/near-zero nonspecific protein adsorption from other proteins that are present. These antifouling zwitterionic polymer-coated beads, therefore, provide a significant advancement for the many bead-based diagnostic and other biosensing applications that require stringent antifouling conditions.

  4. Highly Selective Enrichment of Glycopeptides Based on Zwitterionically Functionalized Soluble Nanopolymers

    Science.gov (United States)

    Cao, Weiqian; Huang, Jiangming; Jiang, Biyun; Gao, Xing; Yang, Pengyuan

    2016-07-01

    Efficient glycopeptides enrichment prior to mass spectrometry analysis is essential for glycoproteome study. ZIC-HILIC (zwitterionic hydrophilic interaction liquid chromatography) based glycopeptides enrichment approaches have been attracting more attention for several benefits like easy operating, high enrichment specificity and intact glycopeptide retained. In this study, Poly (amidoamine) dendrimer (PAMAM) was adopted for the synthesis of zwitterionically functionalized (ZICF) materials for glycopeptide enrichment. The multiple branched structure and good solubility of ZICF-PAMAM enables a sufficient interaction with glycopeptides. The ZICF-PAMAM combined with the FASP-mode enrichment strategy exhibits more superior performance compared with the existing methods. It has the minimum detectable concentration of femtomolar level and high recovery rate of over 90.01%, and can efficiently enrich glycopeptides from complex biological samples even for merely 0.1 μL human serum. The remarkable glycopeptides enrichment capacity of ZICF-PAMAM highlights the potential application in in-depth glycoproteome research, which may open up new opportunities for the development of glycoproteomics.

  5. Stable and biocompatible genipin-inducing interlayer-crosslinked micelles for sustained drug release

    Energy Technology Data Exchange (ETDEWEB)

    Dai, Yu; Zhang, Xiaojin, E-mail: zhangxj@cug.edu.cn [China University of Geosciences, Faculty of Materials Science and Chemistry (China)

    2017-05-15

    To develop the sustained drug release system, here we describe genipin-inducing interlayer-crosslinked micelles crosslinked via Schiff bases between the amines of amphiphilic linear-hyperbranched polymer poly(ethylene glycol)-branched polyethylenimine-poly(ε-caprolactone) (PEG-PEI-PCL) and genipin. The generation of Schiff bases was confirmed by the color changes and UV-Vis absorption spectra of polymeric micelles after adding genipin. The particle size, morphology, stability, in vitro cytotoxicity, drug loading capacity, and in vitro drug release behavior of crosslinked micelles as well as non-crosslinked micelles were characterized. The results indicated that genipin-inducing interlayer-crosslinked micelles had better stability and biocompatibility than non-crosslinked micelles and glutaraldehyde-inducing interlayer-crosslinked micelles. In addition, genipin-inducing interlayer-crosslinked micelles were able to improve drug loading capacity, reduce the initial burst release, and achieve sustained drug release.

  6. Controlled Fab installation onto polymeric micelle nanoparticles for tuned bioactivity

    Science.gov (United States)

    Chen, Shaoyi; Florinas, Stelios; Teitgen, Abigail; Xu, Ze-Qi; Gao, Changshou; Wu, Herren; Kataoka, Kazunori; Cabral, Horacio; Christie, R. James

    2017-12-01

    Antibodies and antigen-binding fragments (Fabs) can be used to modify the surface of nanoparticles for enhanced target binding. In our previous work, site-specific conjugation of Fabs to polymeric micelles using conventional methods was limited to approximately 30% efficiency, possibly due to steric hindrance related to macromolecular reactants. Here, we report a new method that enables conjugation of Fabs onto a micelle surface in a controlled manner with up to quantitative conversion of nanoparticle reactive groups. Variation of (i) PEG spacer length in a heterofunctionalized cross-linker and (ii) Fab/polymer feed ratios resulted in production of nanoparticles with a range of Fab densities on the surface up to the theoretical maximum value. The biological impact of variable Fab density was evaluated in vitro with respect to cell uptake and cytotoxicity of a drug-loaded (SN38) targeted polymeric micelle bearing anti-EphA2 Fabs. Fab conjugation increased cell uptake and potency compared with non-targeted micelles, although a Fab density of 60% resulted in decreased uptake and potency of the targeted micelles. Altogether, our findings demonstrate that conjugation strategies can be optimized to allow control of Fab density on the surface of nanoparticles and also that Fab density may need to be optimized for a given cell-surface target to achieve the highest bioactivity.

  7. Light Scattering Characterization of Elastin-Like Polypeptide Trimer Micelles

    Science.gov (United States)

    Tsuper, Ilona; Terrano, Daniel; Maraschky, Adam; Holland, Nolan; Streletzky, Kiril

    The elastin-like polypeptides (ELP) nanoparticles are composed of three-armed star polypeptides connected by a negatively charged foldon. Each of the three arms extending from the foldon domain includes 20 repeats of the (GVGVP) amino acid sequence. The ELP polymer chains are soluble at room temperature and become insoluble at the transition temperature (close to 50 ° C), forming micelles. The size and shape of the micelle are dependent on the temperature and the pH of the solution, and on the concentration of the phosphate buffered saline (PBS). The depolarized dynamic light scattering (DDLS) was employed to study the structure and dynamics of micelles at 62 ° C. The solution was maintained at an approximate pH level of 7.3 - 7.5, while varying PBS concentration. At low salt concentrations (60 mM) displayed an apparent elongation of the micelles evident by a significant VH signal, along with a surge in the apparent Rh. A model of micelle growth (and potential elongation) with increase in salt concentration is considered.

  8. Effect of microfluidization on casein micelle size of bovine milk

    Science.gov (United States)

    Sinaga, H.; Deeth, H.; Bhandari, B.

    2018-02-01

    The properties of milk are likely to be dependent on the casein micelle size, and various processing technologies produce particular change in the average size of casein micelles. The main objective of this study was to manipulate casein micelle size by subjecting milk to microfluidizer. The experiment was performed as a complete block randomised design with three replications. The sample was passed through the microfluidizer at the set pressure of 83, 97, 112 and 126 MPa for one, two, three, four, five and six cycles, except for the 112 MPa. The results showed that microfluidized milk has smaller size by 3% with pressure up to 126 MPa. However, at each pressure, no further reduction was observed after increasing the passed up to 6 cycles. Although the average casein micelle size was similar, elevating pressure resulted in narrower size distribution. In contrast, increasing the number of cycles had little effect on casein micelle distribution. The finding from this study can be applied for future work to characterize the fundamental and functional properties of the treated milk.

  9. Preclinical safety evaluation of intravenously administered mixed micelles.

    Science.gov (United States)

    Teelmann, K; Schläppi, B; Schüpbach, M; Kistler, A

    1984-01-01

    Mixed micelles, with their main constituents lecithin and glycocholic acid, form a new principle for the parenteral administration of compounds which are poorly water-soluble. Their composition of mainly physiological substances as well as their comparatively good stability substantiate their attractivity in comparison to existing solvents. A decomposition due to physical influences such as heat or storage for several years will almost exclusively affect the lecithin component in the form of hydrolysis into free fatty acids and lysolecithin. Their toxicity was examined experimentally in various studies using both undecomposed and artificially decomposed mixed micelles. In these studies the mixed micelles were locally and systemically well tolerated and proved to be neither embryotoxic, teratogenic nor mutagenic. Only when comparatively high doses of the undecomposed mixed micelles were administered, corresponding to approximately 30 to 50 times the anticipated clinical injection volume (of e.g. diazepam mixed micelles), did some vomitus (dogs), slight liver enzyme elevation (rats and dogs), and slightly increased liver weights (dogs) occur. After repeated injections of the artificially decomposed formulation (approximately 25% of lecithin hydrolyzed to free fatty acids and lysolecithin) effects such as intravascular haemolysis, liver enzyme elevations and intrahepatic cholestasis (dogs only) were observed but only when doses exceeding a threshold of approximately 40 to 60 mg lysolecithin/kg body weight were administered. All alterations were reversible after cessation of treatment.

  10. 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...... insight into optimal design of titration protocols for micelle characterization. By applying the new method, the aggregation number of sodium dodecyl sulphate and glycochenodeoxycholate was determined at concentrations around their critical micelle concentration (CMC)...

  11. 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...

  12. Recovery and redispersion of gold nanoparticles using the self-assembly of a pH sensitive zwitterionic amphiphile.

    Science.gov (United States)

    Morita-Imura, Clara; Imura, Yoshiro; Kawai, Takeshi; Shindo, Hitoshi

    2014-11-04

    The pH-responsive self-assembly of zwitterionic amphiphile C16CA was expanded to the recovery of gold (Au) nanoparticles for environmentally friendly chemistry applications. Multilayered lamellae at pH ∼ 4 were successfully incorporated into nanoparticles by dispersion. Redispersion of nanoparticles was achieved under basic conditions by the transition of self-assembly.

  13. Effects of anions on the zwitterion stability of Glu, His and Arg investigated by IRMPD spectroscopy and theory

    NARCIS (Netherlands)

    O'Brien, J.T.; Prell, J.S.; Berden, G.; Oomens, J.; Williams, E.R.

    2010-01-01

    Interactions of halide anions (Cl-, Br-, and I-) with glutamic acid (Glu), histidine (His), and arginine (Arg) and their effects on stabilizing the zwitterionic form of these amino acids were investigated using infrared multiple photon dissociation (IRMPD) spectroscopy between 850 and 1900 cm(-1)

  14. New carboxy-functionalized terpyridines as precursors for zwitterionic ruthenium complexes for polymer-based solar cells

    DEFF Research Database (Denmark)

    Duprez, V.; Krebs, Frederik C

    2006-01-01

    New carboxy-terpyridines selectively functionalized at the 4-, 4'- and 4"-positions were prepared in a three-step procedure with good yields using, the Krohnke reaction followed by saponification. Their complexation with ruthenium led to symmetric and unsymmetric terpyridinyl zwitterionic complexes...

  15. Micelle fission through surface instability and formation of an interdigitating stalk

    NARCIS (Netherlands)

    Sammalkorpi, M.; Karttunen, M.E.J.; Haataja, M.

    2008-01-01

    We report on the first detailed atomic-scale studies of micelle fission in micellar systems consisting of anionic sodium dodecyl sulfate with explicit solvent. We demonstrate a new micelle fission pathway for ionic surfactants and show how micelle fission can be induced by varying the ionic

  16. 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

  17. 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.

  18. 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.

  19. 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.

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

    KAUST Repository

    Nunes, Suzana Pereira; Karunakaran, Madhavan; Neelakanda, Pradeep; Behzad, Ali Reza; Hooghan, Bobby; Sougrat, Rachid; He, Haoze; Peinemann, Klaus-Viktor

    2011-01-01

    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.

  1. Structural characterization of casein micelles: shape changes during film formation

    International Nuclear Information System (INIS)

    Gebhardt, R; Kulozik, U; Vendrely, C

    2011-01-01

    The objective of this study was to determine the effect of size-fractionation by centrifugation on the film structure of casein micelles. Fractionated casein micelles in solution were asymmetrically distributed with a small distribution width as measured by dynamic light scattering. Films prepared from the size-fractionated samples showed a smooth surface in optical microscopy images and a homogeneous microstructure in atomic force micrographs. The nano- and microstructure of casein films was probed by micro-beam grazing incidence small angle x-ray scattering (μGISAXS). Compared to the solution measurements, the sizes determined in the film were larger and broadly distributed. The measured GISAXS patterns clearly deviate from those simulated for a sphere and suggest a deformation of the casein micelles in the film. (paper)

  2. Charged triblock copolymer self-assembly into charged micelles

    Science.gov (United States)

    Chen, Yingchao; Zhang, Ke; Zhu, Jiahua; Wooley, Karen; Pochan, Darrin; Department of Material Science; Engineering University of Delaware Team; Department of Chemistry Texas A&M University Collaboration

    2011-03-01

    Micelles were formed through the self-assembly of amphiphlic block copolymer poly(acrylic acid)-block-poly(methyl acrylate)-block-polystyrene (PAA-PMA-PS). ~Importantly, the polymer is complexed with diamine molecules in pure THF solution prior to water titration solvent processing-a critical aspect in the control of final micelle geometry. The addition of diamine triggers acid-base complexation ~between the carboxylic acid PAA side chains and amines. ~Remarkably uniform spheres were found to form close-packed patterns when forced into dried films and thin, solvated films when an excess of amine was used in the polymer assembly process. Surface properties and structural features of these hexagonal-packed spherical micelles with charged corona have been explored by various characterization methods including Transmission Electron Microscopy (TEM), cryogenic TEM, z-potential analysis and Dynamic Light Scattering. The forming mechanism for this pattern and morphology changes against external stimulate such as salt will be discussed.

  3. Modification of encapsulation pressure of reverse micelles in liquid ethane.

    Science.gov (United States)

    Peterson, Ronald W; Nucci, Nathaniel V; Wand, A Joshua

    2011-09-01

    Encapsulation within reverse micelles dissolved in low viscosity fluids offers a potential solution to the slow tumbling problem presented by large soluble macromolecules to solution NMR spectroscopy. The reduction in effective macromolecular tumbling is directly dependent upon the viscosity of the solvent. Liquid ethane is of sufficiently low viscosity at pressures below 5000 psi to offer a significant advantage. Unfortunately, the viscosity of liquid ethane shows appreciable pressure dependence. Reverse micelle encapsulation in liquid ethane often requires significantly higher pressures, which obviates the potential advantages offered by liquid ethane over liquid propane. Addition of co-surfactants or co-solvents can be used to manipulate the minimum pressure required to obtain stable, well-behaved solutions of reverse micelles prepared in liquid ethane. A library of potential additives is examined and several candidates suitable for use with encapsulated proteins are described. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. Light and neutron scattering study of strongly interacting ionic micelles

    International Nuclear Information System (INIS)

    Degiorgio, V.; Corti, M.; Piazza, R.

    1989-01-01

    Dilute solutions of ionic micelles formed by biological glycolipids (gangliosides) have been investigated at various ionic strengths by static and dynamic light scaterring and by small-angle neutron scattering. The size and shape of the micelle is not appreciably affected by the added salt concentration in the range 0-100 mM NaCL. From the measured intensity of scattered light we derive the electric charge Z of the micelle by fitting the data to a theoretical calculation which uses a screened Coulomb potential for the intermicellar interaction, and the hypernetted chain approximation for the calculation of the radial distribution function. The correlation function derived from dynamic light scattering shows the long time contribution typical of concentrated polydisperse systems (author). 15 refs.; 6 figs

  5. 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.

  6. Formation of nanoparticles on reverse micelles: SANS studies

    International Nuclear Information System (INIS)

    Sim, Jae-Hyun; Park, Jaejung; Kim, Myungwoong; Hwan Bang, Jeong; Park, Sangwook; Sohn, Daewon

    2006-01-01

    The structure of polymethyl methacrylate (PMMA) on the surface of reverse micelles was investigated by small-angle neutron scattering (SANS). The water-in-oil microemulsion containing initiators in the inner part of reverse micelle was prepared with surfactant, poly(oxyethylene) nonylphenyl ether (NP5, H(CH 2 ) 9 Ph(OC 2 H 4 ) 5 OH), water, cyclohexane and adequate initiators, sodium metabisulfate (SDS) and potassium persulfate (KPS), for aimed polymerization (PMMA). Various model fittings such as the core-shell sphere model and hard sphere model containing smearing effect reveal that polymer shell thickness changes from 52 to 60 A, respectively, with increase of monomer concentration

  7. 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...... solvent mixture) is titrated with a solution of asphaltene in the same solvent. The asphaltene concentration of the injected solution is at a level above the critical micelle concentration (CMC). In the present paper the procedure is applied in investigation of asphaltenes as well as subfractions...

  8. Core-Shell-Corona Micelles with a Responsive Shell.

    Science.gov (United States)

    Gohy, Jean-François; Willet, Nicolas; Varshney, Sunil; Zhang, Jian-Xin; Jérôme, Robert

    2001-09-03

    A reactor for the synthesis of gold nanoparticles is one of the uses of a poly(styrene)-block-poly(2-vinylpyridine)-block-poly(ethylene oxide) triblock copolymer (PS-b-P2VP-b-PEO) which forms core-shell-corona micelles in water. Very low polydispersity spherical micelles are observed that consist of a PS core surrounded by a pH-sensitive P2VP shell and a corona of PEO chains end-capped by a hydroxyl group. The corona can act as a site for attaching responsive or sensing molecules. © 2001 WILEY-VCH Verlag GmbH, Weinheim, Fed. Rep. of Germany.

  9. 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

  10. Preparation of PES ultrafiltration membranes with natural amino acids based zwitterionic antifouling surfaces

    International Nuclear Information System (INIS)

    Xu, Chen; Liu, Xiaojiu; Xie, Binbin; Yao, Chen; Hu, Wenhan; Li, Yi; Li, Xinsong

    2016-01-01

    Highlights: • Amino acids have been successfully grafted onto the surface of PES membranes via amino groups induced epoxy ring opening. • Zwitterionic PES ultrafiltration membranes exhibit excellent antifouling performance and improved permeation properties. • A facile strategy to combat fouling of PES ultrafiltration membranes is developed by grafting natural amino acids. - Abstract: In this report, a simple and facile approach to enhance the antifouling property of poly(ether sulfone) (PES) ultrafiltration membrane was developed by grafting natural amino acids onto surface. First of all, poly(ether sulfone) composite membranes blended with poly(glycidyl methacrylate) were fabricated by phase inversion method followed by grafting of different types of natural amino acids onto the membrane surface through epoxy ring opening reaction. The analysis of attenuated total reflectance Fourier transform infrared spectroscopy (ATR/FTIR) and X-ray photoelectron spectroscopy (XPS) verified the substantial enrichment of amino acids onto the surface of PES membranes. The hydrophilicity of the PES membranes was improved after grafting amino acids. The mechanical property and morphologies of the PES membranes proved that their basic performances were not obviously affected by grafting reaction, and these parameters were all still in the typical range for ultrafiltration membranes. The antifouling property of the grafted PES membranes against bovine serum albumin (BSA) and lysozyme (Lyz) was investigated in detail. It was found that PES membranes incorporated with neutral amino acids exhibited higher fouling resistance to both BSA and Lyz than the parent PES membrane. It can be ascribed to the formation of zwitterionic structure on the surface consisting of protonated secondary amino cations and carboxyl anions. Meanwhile, PES membranes grafted with charged amino acids had better antifouling properties against protein with same electric charges and improved adsorption

  11. Preparation of PES ultrafiltration membranes with natural amino acids based zwitterionic antifouling surfaces

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Chen; Liu, Xiaojiu; Xie, Binbin; Yao, Chen [School of Chemistry and Chemical Engineering, Southeast University, Nanjing, 211189 (China); Hu, Wenhan; Li, Yi [Suzhou Faith & Hope Membrane Technology Co., Ltd., Suzhou, 215000 (China); Li, Xinsong, E-mail: lixs@seu.edu.cn [School of Chemistry and Chemical Engineering, Southeast University, Nanjing, 211189 (China)

    2016-11-01

    Highlights: • Amino acids have been successfully grafted onto the surface of PES membranes via amino groups induced epoxy ring opening. • Zwitterionic PES ultrafiltration membranes exhibit excellent antifouling performance and improved permeation properties. • A facile strategy to combat fouling of PES ultrafiltration membranes is developed by grafting natural amino acids. - Abstract: In this report, a simple and facile approach to enhance the antifouling property of poly(ether sulfone) (PES) ultrafiltration membrane was developed by grafting natural amino acids onto surface. First of all, poly(ether sulfone) composite membranes blended with poly(glycidyl methacrylate) were fabricated by phase inversion method followed by grafting of different types of natural amino acids onto the membrane surface through epoxy ring opening reaction. The analysis of attenuated total reflectance Fourier transform infrared spectroscopy (ATR/FTIR) and X-ray photoelectron spectroscopy (XPS) verified the substantial enrichment of amino acids onto the surface of PES membranes. The hydrophilicity of the PES membranes was improved after grafting amino acids. The mechanical property and morphologies of the PES membranes proved that their basic performances were not obviously affected by grafting reaction, and these parameters were all still in the typical range for ultrafiltration membranes. The antifouling property of the grafted PES membranes against bovine serum albumin (BSA) and lysozyme (Lyz) was investigated in detail. It was found that PES membranes incorporated with neutral amino acids exhibited higher fouling resistance to both BSA and Lyz than the parent PES membrane. It can be ascribed to the formation of zwitterionic structure on the surface consisting of protonated secondary amino cations and carboxyl anions. Meanwhile, PES membranes grafted with charged amino acids had better antifouling properties against protein with same electric charges and improved adsorption

  12. 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

  13. Static structure factor of polymerlike micelles: Overall dimension, flexibility, and local properties of lecithin reverse micelles in deuterated isooctane

    DEFF Research Database (Denmark)

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

    1997-01-01

    We report a systematic investigation of the static structure factor S(q,c) of polymerlike reverse micelles formed by soybean lecithin and trace amounts of water in deuterated isooctane using small-angle neutron scattering and static light scattering. The experimental data for different concentrat......We report a systematic investigation of the static structure factor S(q,c) of polymerlike reverse micelles formed by soybean lecithin and trace amounts of water in deuterated isooctane using small-angle neutron scattering and static light scattering. The experimental data for different...

  14. Unfolding a molecular trefoil derived from a zwitterionic metallopeptide to form self-assembled nanostructures

    KAUST Repository

    Zhang, Ye; Zhou, Ning; Shi, Junfeng; Pochapsky, Susan Sondej; Pochapsky, Thomas C.; Zhang, Bei; Zhang, Xixiang; Xu, Bing

    2015-01-01

    While used extensively by nature to control the geometry of protein structures, and dynamics of proteins, such as self-organization, hydration forces and ionic interactions received less attention for controlling the behaviour of small molecules. Here we describe the synthesis and characterization of a novel zwitterionic metallopeptide consisting of a cationic core and three distal anionic groups linked by self-assembling peptide motifs. 2D NMR spectra, total correlated spectroscopy and nuclear Overhauser effect spectroscopy, show that the molecule exhibits a three-fold rotational symmetry and adopts a folded conformation in dimethyl sulfoxide due to Coulombic forces. When hydrated in water, the molecule unfolds to act as a self-assembling building block of supramolecular nanostructures. By combining ionic interactions with the unique geometry from metal complex and hydrophobic interactions from simple peptides, we demonstrate a new and effective way to design molecules for smart materials through mimicking a sophisticated biofunctional system using a conformational switch.

  15. Unfolding a molecular trefoil derived from a zwitterionic metallopeptide to form self-assembled nanostructures

    KAUST Repository

    Zhang, Ye

    2015-02-19

    While used extensively by nature to control the geometry of protein structures, and dynamics of proteins, such as self-organization, hydration forces and ionic interactions received less attention for controlling the behaviour of small molecules. Here we describe the synthesis and characterization of a novel zwitterionic metallopeptide consisting of a cationic core and three distal anionic groups linked by self-assembling peptide motifs. 2D NMR spectra, total correlated spectroscopy and nuclear Overhauser effect spectroscopy, show that the molecule exhibits a three-fold rotational symmetry and adopts a folded conformation in dimethyl sulfoxide due to Coulombic forces. When hydrated in water, the molecule unfolds to act as a self-assembling building block of supramolecular nanostructures. By combining ionic interactions with the unique geometry from metal complex and hydrophobic interactions from simple peptides, we demonstrate a new and effective way to design molecules for smart materials through mimicking a sophisticated biofunctional system using a conformational switch.

  16. Palladium catalyst system comprising zwitterion and/or acid-functionalized ionic liquid

    DEFF Research Database (Denmark)

    2011-01-01

    The present invention concerns a catalyst system in particular a catalyst system comprising Palladium (Pd), a zwitterion and/or an acid-functionalized ionic liquid, and one or more phosphine ligands, wherein the Pd catalyst can be provided by a complex precursor, such as Pd(CH3COO)2, PdCI2, Pd(CH3......COCHCOCH3), Pd (CF3COO)2, Pd(PPh3)4 or Pd2(dibenzylideneacetone)3. Such catalyst systems can be used for e.g. alkoxycarbonylation reactions, carboxylation reactions, and/or in a co-polymerization reaction, e.g. in the production of methyl propionate and/or propanoic acid, optionally in processes forming...... methyl methacrylate and/or methacrylic acid. Catalyst systems according to the invention are suitable for reactions forming separable product and catalyst phases and supported ionic liquid phase SILP applications....

  17. Poly(zwitterionic)protein conjugates offer increased stability without sacrificing binding affinity or bioactivity

    Science.gov (United States)

    Keefe, Andrew J.; Jiang, Shaoyi

    2012-01-01

    Treatment with therapeutic proteins is an attractive approach to targeting a number of challenging diseases. Unfortunately, the native proteins themselves are often unstable in physiological conditions, reducing bioavailability and therefore increasing the dose that is required. Conjugation with poly(ethylene glycol) (PEG) is often used to increase stability, but this has a detrimental effect on bioactivity. Here, we introduce conjugation with zwitterionic polymers such as poly(carboxybetaine). We show that poly(carboxybetaine) conjugation improves stability in a manner similar to PEGylation, but that the new conjugates retain or even improve the binding affinity as a result of enhanced protein-substrate hydrophobic interactions. This chemistry opens a new avenue for the development of protein therapeutics by avoiding the need to compromise between stability and affinity.

  18. Interactions of a zwitterionic thiophene-based conjugated polymer with surfactants

    DEFF Research Database (Denmark)

    Costa, Telma; De Azevedo, Diego; Stewart, Beverly

    2015-01-01

    In this paper we investigate the optical and structural properties of a zwitterionic poly[3-(N-(4-sulfonato-1-butyl)-N,N-diethylammonium)hexyl-2,5-thiophene] (P3SBDEAHT) conjugated polyelectrolyte (CPE) and its interaction in water with surfactants, using absorption, photoluminescence (PL......), electrical conductivity, molecular dynamics simulations (MDS) and small-angle X-ray scattering (SAXS). Different surfactants were studied to evaluate the effect of the head group and chain length on the self-assembly. PL data emphasize the importance of polymer-surfactant electrostatic interactions...... in the formation of complexes. Nevertheless, conductivity and MDS data have shown that nonspecific interactions also play an important role. These seem to be responsible for the spatial position of the surfactant tail in the complex and, eventually, for breaking-up P3SBDEAHT aggregates. SAXS measurements on P3...

  19. Applying thermosettable zwitterionic copolymers as general fouling-resistant and thermal-tolerant biomaterial interfaces.

    Science.gov (United States)

    Chou, Ying-Nien; Chang, Yung; Wen, Ten-Chin

    2015-05-20

    We introduced a thermosettable zwitterionic copolymer to design a high temperature tolerance biomaterial as a general antifouling polymer interface. The original synthetic fouling-resistant copolymer, poly(vinylpyrrolidone)-co-poly(sulfobetaine methacrylate) (poly(VP-co-SBMA)), is both thermal-tolerant and fouling-resistant, and the antifouling stability of copolymer coated interfaces can be effectively controlled by regulating the VP/SBMA composition ratio. We studied poly(VP-co-SBMA) copolymer gels and networks with a focus on their general resistance to protein, cell, and bacterial bioadhesion, as influenced by the thermosetting process. Interestingly, we found that the shape of the poly(VP-co-SBMA) copolymer material can be set at a high annealing temperature of 200 °C while maintaining good antifouling properties. However, while the zwitterionic PSBMA polymer gels were bioinert as expected, control of the fouling resistance of the PSBMA polymer networks was lost in the high temperature annealing process. A poly(VP-co-SBMA) copolymer network composed of PSBMA segments at 32 mol % showed reduced fibrinogen adsorption, tissue cell adhesion, and bacterial attachment, but a relatively higher PSBMA content of 61 mol % was required to optimize resistance to platelet adhesion and erythrocyte attachment to confer hemocompatibility to human blood. We suggest that poly(VP-co-SBMA) copolymers capable of retaining stable fouling resistance after high temperature shaping have a potential application as thermosettable materials in a bioinert interface for medical devices, such as the thermosettable coating on a stainless steel blood-compatible metal stent investigated in this study.

  20. The structure of ions and zwitterionic lipids regulates the charge of dipolar membranes.

    Science.gov (United States)

    Szekely, Or; Steiner, Ariel; Szekely, Pablo; Amit, Einav; Asor, Roi; Tamburu, Carmen; Raviv, Uri

    2011-06-21

    In pure water, zwitterionic lipids form lamellar phases with an equilibrium water gap on the order of 2 to 3 nm as a result of the dominating van der Waals attraction between dipolar bilayers. Monovalent ions can swell those neutral lamellae by a small amount. Divalent ions can adsorb onto dipolar membranes and charge them. Using solution X-ray scattering, we studied how the structure of ions and zwitterionic lipids regulates the charge of dipolar membranes. We found that unlike monovalent ions that weakly interact with all of the examined dipolar membranes, divalent and trivalent ions adsorb onto membranes containing lipids with saturated tails, with an association constant on the order of ∼10 M(-1). One double bond in the lipid tail is sufficient to prevent divalent ion adsorption. We suggest that this behavior is due to the relatively loose packing of lipids with unsaturated tails that increases the area per lipid headgroup, enabling their free rotation. Divalent ion adsorption links two lipids and limits their free rotation. The ion-dipole interaction gained by the adsorption of the ions onto unsaturated membranes is insufficient to compensate for the loss of headgroup free-rotational entropy. The ion-dipole interaction is stronger for cations with a higher valence. Nevertheless, polyamines behave as monovalent ions near dipolar interfaces in the sense that they interact weakly with the membrane surface, whereas in the bulk their behavior is similar to that of multivalent cations. Advanced data analysis and comparison with theory provide insight into the structure and interactions between ion-induced regulated charged interfaces. This study models biologically relevant interactions between cell membranes and various ions and the manner in which the lipid structure governs those interactions. The ability to monitor these interactions creates a tool for probing systems that are more complex and forms the basis for controlling the interactions between dipolar

  1. Thermodynamics of micelle formation in a water-alcohol solution of sodium tetradecyl sulfate

    Science.gov (United States)

    Shilova, S. V.; Tret'yakova, A. Ya.; Barabanov, V. P.

    2016-01-01

    The effects of addition of ethanol and propan-1-ol on sodium tetradecyl sulfate micelle formation in an aqueous solution are studied via microprobe fluorescence microscopy and conductometry. The critical micelle concentration, quantitative characteristics of micelles, and thermodynamic parameters of micelle formation are determined. Addition of 5-15 vol % of ethanol or 5-10 vol % of propan-1-ol is shown to result in a lower critical micelle concentration than in the aqueous solution, and in the formation of mixed spherical micelles whose sizes and aggregation numbers are less than those for the systems without alcohol. The contribution from the enthalpy factor to the free energy of sodium tetradecyl sulfate micelle formation is found to dominate in mixed solvents, in contrast to aqueous solutions.

  2. Micelles as delivery vehicles for oligofluorene for bioimaging.

    Science.gov (United States)

    Su, Fengyu; Alam, Ruhaniyah; Mei, Qian; Tian, Yanqing; Meldrum, Deirdre R

    2011-01-01

    With the successful development of organic/polymeric light emitting diodes, many organic and polymeric fluorophores with high quantum efficiencies and optical stability were synthesized. However, most of these materials which have excellent optical properties are insoluble in water, limiting their applications in biological fields. Herein, we used micelles formed from an amino-group-containing poly(ε-caprolactone)-block-poly(ethylene glycol) (PCL-b-PEG-NH(2)) to incorporate a hydrophobic blue emitter oligofluorene (OF) to enable its application in biological conditions. Although OF is completely insoluble in water, it was successfully transferred into aqueous solutions with a good retention of its photophysical properties. OF exhibited a high quantum efficiency of 0.84 in a typical organic solvent of tetrahydrofuran (THF). In addition, OF also showed a good quantum efficiency of 0.46 after being encapsulated into micelles. Two cells lines, human glioblastoma (U87MG) and esophagus premalignant (CP-A), were used to study the cellular internalization of the OF incorporated micelles. Results showed that the hydrophobic OF was located in the cytoplasm, which was confirmed by co-staining the cells with nucleic acid specific SYTO 9, lysosome specific LysoTracker Red®, and mitochondria specific MitoTracker Red. MTT assay indicated non-toxicity of the OF-incorporated micelles. This study will broaden the application of hydrophobic functional organic compounds, oligomers, and polymers with good optical properties to enable their applications in biological research fields.

  3. Micelles as delivery vehicles for oligofluorene for bioimaging.

    Directory of Open Access Journals (Sweden)

    Fengyu Su

    Full Text Available With the successful development of organic/polymeric light emitting diodes, many organic and polymeric fluorophores with high quantum efficiencies and optical stability were synthesized. However, most of these materials which have excellent optical properties are insoluble in water, limiting their applications in biological fields. Herein, we used micelles formed from an amino-group-containing poly(ε-caprolactone-block-poly(ethylene glycol (PCL-b-PEG-NH(2 to incorporate a hydrophobic blue emitter oligofluorene (OF to enable its application in biological conditions. Although OF is completely insoluble in water, it was successfully transferred into aqueous solutions with a good retention of its photophysical properties. OF exhibited a high quantum efficiency of 0.84 in a typical organic solvent of tetrahydrofuran (THF. In addition, OF also showed a good quantum efficiency of 0.46 after being encapsulated into micelles. Two cells lines, human glioblastoma (U87MG and esophagus premalignant (CP-A, were used to study the cellular internalization of the OF incorporated micelles. Results showed that the hydrophobic OF was located in the cytoplasm, which was confirmed by co-staining the cells with nucleic acid specific SYTO 9, lysosome specific LysoTracker Red®, and mitochondria specific MitoTracker Red. MTT assay indicated non-toxicity of the OF-incorporated micelles. This study will broaden the application of hydrophobic functional organic compounds, oligomers, and polymers with good optical properties to enable their applications in biological research fields.

  4. Small angle neutron scattering studies of mixed micelles of sodium

    Indian Academy of Sciences (India)

    The aqueous solutions of sodium cumene sulphonate (NaCS) and its mixtures with each of cetyl trimethylammonium bromide (CTAB) and sodium dodecyl sulphate (SDS) are characterized by small angle neutron scattering (SANS). NaCS when added to CTAB solution leads to the formation of long rod-shaped micelles with ...

  5. Applications of polymeric micelles with tumor targeted in chemotherapy

    International Nuclear Information System (INIS)

    Ding Hui; Wang Xiaojun; Zhang Song; Liu Xinli

    2012-01-01

    Polymeric micelles (PMs) have gained more progress as a carrier system with the quick development of biological and nanoparticle techniques. In particular, PMs with smart targeting can deliver anti-cancer drugs directly into tumor cells at a sustained rate. PMs with core–shell structure (with diameters of 10 ∼ 100 nm) have been prepared by a variety of biodegradable and biocompatible polymers via a self-assembly process. The preparation of polymeric micelles with stimuli-responsive block copolymers or modification of target molecules on polymeric micelles’ surface are able to significantly improve the efficiency of drug delivery. Polymeric micelles, which have been considered as a novel promising drug carrier for cancer therapeutics, are rapidly evolving and being introduced in an attempt to overcome several limitations of traditional chemotherapeutics, including water solubility, tumor-specific accumulation, anti-tumor efficacy, and non-specific toxicity. This review describes the preparation of polymeric micelles and the targeted modification which greatly enhance the effects of chemotherapeutic agents.

  6. 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...

  7. Reversibility and Relaxation Behavior of Polyelectrolyte Complex Micelle Formation

    NARCIS (Netherlands)

    Lindhoud, Saskia; Norde, Willem; Stuart, Martien A. Cohen

    2009-01-01

    In this study, the formation and disintegration of polyelectrolyte complex micelles is studied by dynamic light scattering titrations with the aim to assess the extent to which these complexes equilibrate. Also, the time evolution of samples at fixed (electroneutral) composition was followed to

  8. Flow of wormlike micelles in an expansion-contraction geometry

    NARCIS (Netherlands)

    Stukan, Mikhail R.; Boek, Edo S.; Boek, E.S.; Padding, J.T.; Briels, Willem J.; Crawshaw, John P.

    2008-01-01

    Recently there has been a great deal of attention, from researchers both in academia and in industry, focused on the rheological properties of solutions of viscoelastic wormlike micelles formed by surfactants. It is particularly vital to understand the properties of these solutions with regard to

  9. Investigating Block-Copolymer Micelle Dynamics for Tunable Cargo Delivery

    Science.gov (United States)

    Li, Xiuli; Kidd, Bryce; Cooksey, Tyler; Robertson, Megan; Madsen, Louis

    Block-copolymer micelles (BCPMs) can carry molecular cargo in a nanoscopic package that is tunable using polymer structure in combination with cargo properties, as well as with external stimuli such as temperature or pH. For example, BCPMs can be used in targeted anticancer drug delivery due to their biocompatibility, in vivo degradability and prolonged circulation time. We are using NMR spectroscopy and diffusometry as well as SANS to investigate BCPMs. Here we study a diblock poly(ethylene oxide)-b-(caprolactone) (PEO-PCL) that forms spherical micelles at 1% (w/v) in the mixed solvent D2O/THF-d8. We quantify the populations and diffusion coefficients of coexisting micelles and free unimers over a range of temperatures and solvent compositions. We use temperature as a stimulus to enhance unimer exchange and hence trigger cargo release, in some cases at a few degrees above body temperature. We present evidence for dominance of the insertion-expulsion mechanism of unimer exchange in these systems, and we map phase diagrams versus temperature and solvent composition. This study sheds light on how intermolecular interactions fundamentally affect cargo release, unimer exchange, and overall micelle tunability.

  10. High-frequency ultrasound-responsive block copolymer micelle.

    Science.gov (United States)

    Wang, Jie; Pelletier, Maxime; Zhang, Hongji; Xia, Hesheng; Zhao, Yue

    2009-11-17

    Micelles of a diblock copolymer composed of poly(ethylene oxide) and poly(2-tetrahydropyranyl methacrylate) (PEO-b-PTHPMA) in aqueous solution could be disrupted by high-frequency ultrasound (1.1 MHz). It was found that, upon exposure to a high-intensity focused ultrasound (HIFU) beam at room temperature, the pH value of the micellar solution decreased over irradiation time. The infrared spectroscopic analysis of solid block copolymer samples collected from the ultrasound irradiated micellar solution revealed the formation of carboxylic acid dimers and hydroxyl groups. These characterization results suggest that the high-frequency HIFU beam could induce the hydrolysis reaction of THPMA at room temperature resulting in the cleavage of THP groups. The disruption of PEO-b-PTHPMA micelles by ultrasound was investigated by using dynamic light scattering, atomic force microscopy, and fluorescence spectroscopy. On the basis of the pH change, it was found that the disruption process was determined by a number of factors such as the ultrasound power, the micellar solution volume and the location of the focal spot of the ultrasound beam. This study shows the potential to develop ultrasound-sensitive block copolymer micelles by having labile chemical bonds in the polymer structure, and to use the high-frequency HIFU to trigger a chemical reaction for the disruption of micelles.

  11. Colorful packages : fluorescent proteins in complex coacervate core micelles

    NARCIS (Netherlands)

    Nolles, Antsje

    2018-01-01

    This thesis explores the encapsulation of fluorescent proteins (FPs) into complex coacervate core micelles (C3Ms) and features the impact of this encapsulation on the biophysical properties of the FPs. In total eight different FPs were investigated originating from two different classes

  12. 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 (30...

  13. Coupled Organoclay/Micelle Action for the Adsorption of Diclofenac.

    Science.gov (United States)

    De Oliveira, Tiago; Guégan, Régis

    2016-09-20

    A Na-smectite clay mineral (Na-Mt) was exchanged with various amounts of benzyldimethyltetradecyl ammonium chloride cationic surfactant (BDTAC) up to four times the cation exchange capacity (CEC). The adsorption properties of these organoclays as well as a coupled micelle/organoclay process were evaluated to remove an anionic pharmaceutical product, the diclofenac (DCF), recognized as a recalcitrant compound for conventional water treatments and to be poorly adsorbed onto untreated clay mineral. The DCF affinity appears to depend on the lipophilic character of organoclays in correlation to the density of intercalated BDTA and is particularly enhanced for sorbent systems with free surfactant or micelle in solution. The combination of both organclay and BDTA in excess or micelle as a one pot adsorption system appears to be the most efficient material for the sequestration of DCF and other pharmaceutical products (PPs) with a KF Freundlich constant of 1.7 L g(-1) and no restriction of the adsorbed DCF amount as the linear adsorption isotherm shows. A BDTA hydrophobic core micelle coupled with a positive electric charge forms an organic complex with DCF that is properly intercalated within the interlayer space of BDTA-Mt organoclays as both Fourier transform infrared (FTIR) and X-ray diffraction (XRD) data supported.

  14. Clinical application of polymeric micelles for the treatment of cancer

    NARCIS (Netherlands)

    Varela Moreira, A.A.; Shi, Y.; Fens, M.H.A.M.; Lammers, T.G.G.M.; Hennink, W.E.; Schiffelers, R.M.

    2017-01-01

    The in vivo administration of chemotherapeutic drugs is a challenge due to their poor pharmacokinetic (PK) and biodistribution profiles. For this reason, the development of delivery systems capable of targeting these compounds to pathological sites is of great importance. Polymeric micelles (PMs)

  15. Quenching mechanism of exciplex fluorescence by inverted micelles

    International Nuclear Information System (INIS)

    Sato, Chika; Kikuchi, Koichi

    1992-01-01

    Using an emission-absorption laser photolysis method, the quenching mechanism of the pyrene-N,N-dimethylaniline exciplex fluorscence by inverted micelles is studied. The rate of enhanced intersystem crossing depends upon water pool size and is reduced by external magnetic fields. 15 refs., 3 figs., 2 tabs

  16. Complex coacervate core micelles with a lysozyme-modified corona

    NARCIS (Netherlands)

    Danial, Maarten; Klok, Harm-Anton; Norde, Willem; Stuart, Martien A. Cohen

    2007-01-01

    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.

  17. 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...

  18. 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

  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. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  20. Glyco-Nanoparticles Made from Self-Assembly of Maltoheptaose-block-Poly(methyl methacrylate): Micelle, Reverse Micelle, and Encapsulation.

    Science.gov (United States)

    Zepon, Karine M; Otsuka, Issei; Bouilhac, Cécile; Muniz, Edvani C; Soldi, Valdir; Borsali, Redouane

    2015-07-13

    The synthesis and the solution-state self-assembly of the "hybrid" diblock copolymers, maltoheptaose-block-poly(methyl methacrylate) (MH-b-PMMA), into large compound micelles (LCMs) and reverve micelle-type nanoparticles, are reported in this paper. The copolymers were self-assembled in water and acetone by direct dissolution method, and the morphologies of the nanoparticles were investigated by dynamic light scattering (DLS), nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), atomic force microscopy (AFM), proton nuclear magnetic resonance ((1)H NMR), and fluorescence spectroscopy as a function of the volume fraction of the copolymer hydrophobic block, copolymer concentration, stirring speed, and solvent polarity. The DLS measurements and TEM images showed that the hydrodynamic radius (Rh) of the LCMs obtained in water increases with the copolymer concentration. Apart from that, increasing the stirring speed leads to polydispersed aggregations of the LCMs. On the other hand, in acetone, the copolymers self-assembled into reverse micelle-type nanoparticles having Rh values of about 6 nm and micellar aggregates, as revealed the results obtained from DLS, AFM, and (1)H NMR analyses. The variation in micellar structure, that is, conformational inversion from LCMs to reverse micelle-type structures in response to polarity of the solvent, was investigated by apparent water contact angle (WCA) and (1)H NMR analyses. This conformational inversion of the nanoparticles was further confirmed by encapsulation and release of hydrophobic guest molecule, Nile red, characterized by fluorescence spectroscopy.

  1. 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

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

    International Nuclear Information System (INIS)

    Ingemann Jensen, A.T.

    2013-01-01

    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

  3. Lecithin in mixed micelles attenuates the cytotoxicity of bile salts in Caco-2 cells.

    Science.gov (United States)

    Tan, Ya'nan; Qi, Jianping; Lu, Yi; Hu, Fuqiang; Yin, Zongning; Wu, Wei

    2013-03-01

    This study was designed to investigate the cytotoxicity of bile salt-lecithin mixed micelles on the Caco-2 cell model. Cell viability and proliferation after mixed micelles treatments were evaluated with the MTT assay, and the integrity of Caco-2 cell monolayer was determined by quantitating the transepithelial electrical resistance and the flux of tracer, FITC-dextran 4400. The apoptosis induced by mixed micelles treatments was investigated with the annexin V/PI protocol. The particle size of mixed micelles was all smaller than 100 nm. The mixed micelles with lower than 0.2mM sodium deoxycholate (SDC) had no significant effects on cell viability and proliferation. When the level of SDC was higher than 0.4mM and the lecithin/SDC ratio was lower than 2:1, the mixed micelles caused significant changes in cell viability and proliferation. Furthermore, the mixed micelles affected tight junctions in a composition-dependent manner. Specifically, the tight junctions were transiently opened rather than damaged by the mixed micelles with SDC of between 0.2 and 0.6mM. The mixed micelles with more lecithin also induced less apoptosis. These results demonstrate that relatively higher concentrations of mixed micelles are toxic to Caco-2 cells, while phospholipids can attenuate the toxicity of the bile salts. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

  4. Calculations of critical micelle concentration by dissipative particle dynamics simulations: the role of chain rigidity.

    Science.gov (United States)

    Lee, Ming-Tsung; Vishnyakov, Aleksey; Neimark, Alexander V

    2013-09-05

    Micelle formation in surfactant solutions is a self-assembly process governed by complex interplay of solvent-mediated interactions between hydrophilic and hydrophobic groups, which are commonly called heads and tails. However, the head-tail repulsion is not the only factor affecting the micelle formation. For the first time, we present a systematic study of the effect of chain rigidity on critical micelle concentration and micelle size, which is performed with the dissipative particle dynamics simulation method. Rigidity of the coarse-grained surfactant molecule was controlled by the harmonic bonds set between the second-neighbor beads. Compared to flexible molecules with the nearest-neighbor bonds being the only type of bonded interactions, rigid molecules exhibited a lower critical micelle concentration and formed larger and better-defined micelles. By varying the strength of head-tail repulsion and the chain rigidity, we constructed two-dimensional diagrams presenting how the critical micelle concentration and aggregation number depend on these parameters. We found that the solutions of flexible and rigid molecules that exhibited approximately the same critical micelle concentration could differ substantially in the micelle size and shape depending on the chain rigidity. With the increase of surfactant concentration, primary micelles of more rigid molecules were found less keen to agglomeration and formation of nonspherical aggregates characteristic of flexible molecules.

  5. Glycopolymer micelles with reducible ionic cores for hepatocytes-targeting delivery of DOX.

    Science.gov (United States)

    Wang, Yanxia; Zhang, Xinge; Yu, Peien; Li, Chaoxing

    2013-01-30

    A novel galactose-decorated cross-linked micelles (cl-micelles) with ionic cores using cystamine (Cys) as a biodegradable cross-linker was prepared by using block ionomer complexes of poly(ethylene glycol)-b-poly(2-acryloxyethyl-galactose)-b-poly(acrylic acid) (PEG-b-PAEG-b-PAA) and Ca(2+) (PEG-b-PAEG-b-PAA cl-micelles/Cys). Doxorubicin (DOX) was successfully incorporated into the ionic cores of such micelles via electrostatic interactions. Proton nuclear magnetic resonance spectrum and Fourier transform infrared spectrometer indicated galactose ligands were exposed at the micellar surface. The micelles were spherical in shape, with an average size of 100nm. The in vitro release studies confirmed that DOX-loaded PEG-b-PAEG-b-PAA cl-micelles/Cys accomplished rapid drug release under reducing condition. Remarkably, PEG-b-PAEG-b-PAA cl-micelles/Cys efficiently delivered and released DOX into the cell nucleus of HepG2 cells, and the intensity of fluorescence observed in HepG2 cells was stronger than that incubated with the micelles without galactose ligands. In contrast, little fluorescence was observed in NIH3T3 cells after incubation with PEG-b-PAEG-b-PAA cl-micelles/Cys. Interestingly, cytotoxicity assays showed that DOX-loaded PEG-b-PAEG-b-PAA cl-micelles/Cys retained higher cell inhibition efficiency in HepG2 cells as compared with NIH3T3 cells, and were more potent than the micelles without galactose ligands and the micelles with non degradable cross-links. These results indicate that PEG-b-PAEG-b-PAA cl-micelles/Cys have great potential in liver tumor-targeted chemotherapy. Copyright © 2012 Elsevier B.V. All rights reserved.

  6. Poly(zwitterionic liquids) functionalized polypyrrole/graphene oxide nanosheets for electrochemically detecting dopamine at low concentration

    Energy Technology Data Exchange (ETDEWEB)

    Mao, Hui; Liang, Jiachen; Ji, Chunguang; Zhang, Haifeng; Pei, Qi; Zhang, Yuyang; Zhang, Yu [Liaoning Key Laboratory for Green Synthesis and Preparative Chemistry of Advanced Materials, College of Chemistry, Liaoning University, Shenyang 110036 (China); Hisaeda, Yoshio [Department of Chemistry and Biochemistry, Graduate School of Engineering, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395 (Japan); Song, Xi-Ming, E-mail: songlab@lnu.edu.cn [Liaoning Key Laboratory for Green Synthesis and Preparative Chemistry of Advanced Materials, College of Chemistry, Liaoning University, Shenyang 110036 (China); Department of Chemistry and Biochemistry, Graduate School of Engineering, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395 (Japan)

    2016-08-01

    Poly(3-(1-vinylimidazolium-3-yl)propane-1-sulfonate) (PVIPS), a novel kind of poly(zwitterionic liquids) (PZILs) containing both imidazolium cation and sulfonate anion, was successfully modified on the surface of polypyrrole/graphene oxide nanosheets (PPy/GO) by covalent bonding. The obtained novel PZILs functionalized PPy/GO nanosheets (PVIPS/PPy/GO) modified glassy carbon electrode (GCE) presented the excellent electrochemical catalytic activity towards dopamine (DA) with high stability, sensitivity, selectivity and wide linear range (40–1220 nM), especially having a lower detection limit (17.3 nM). The excellent analytical performance is attributed to the strongly negative charges on the surface of modified GCE in aqueous solution, which is different from conventional poly(ionic liquids) modified GCE. DA cations could be quickly enriched on the electrode surface by electrostatic interaction in solution due to the existence of −SO{sub 3}{sup −} groups with negative charge at the end of pendant groups in zwitterionic PVIPS, resulting in a change of the electrons transmission mode in the oxidation of DA, that is, from a typical diffusion-controlled process at conventional poly(1-vinyl-3-ethylimidazole bromide) (PVEIB)/PPy/GO modified GCE to a typical surface-controlled process. - Graphical Abstract: Novel poly(zwitterionic liquids) functionalized polypyrrole/graphene oxide nanosheets were successfully synthesized and presented an excellent performance for determination to DA. Display Omitted - Highlights: • Zwitterionic PVIPS functionalized PPy/GO nanosheets were successfully synthesized. • Their surface charge property has been obviously changed to electronegativity. • The excellent electrochemical catalytic activities towards DA were achieved. • −SO{sub 3}{sup −} groups with negative charge changed the transmission mode of electrons. • PVIPS/PPy/GO can act as an electrode material for detecting DA at low concentration.

  7. Determination of acid-base dissociation constants of very weak zwitterionic heterocyclic bases by capillary zone electrophoresis

    Czech Academy of Sciences Publication Activity Database

    Ehala, Sille; Grishina, Anastasia; Sheshenev, Andrey; Lyapkalo, Ilya; Kašička, Václav

    2010-01-01

    Roč. 1217, - (2010), s. 8048-8053 ISSN 0021-9673 R&D Projects: GA ČR(CZ) GA203/08/1428; GA ČR(CZ) GA203/09/0675 Institutional research plan: CEZ:AV0Z40550506 Keywords : acidity constant * capillary zone electrophoresis * zwitterionic heterocyclic bases Subject RIV: CC - Organic Chemistry Impact factor: 4.194, year: 2010

  8. Hemocompatibility improvement of poly(ethylene terephthalate) via self-polymerization of dopamine and covalent graft of zwitterions

    Energy Technology Data Exchange (ETDEWEB)

    Cai, Xianmei; Yuan, Jiang, E-mail: bioalchem@yahoo.com; Chen, Shuangchun; Li, Pengfei; Li, Li, E-mail: lili3@njnu.edu.cn; Shen, Jian

    2014-03-01

    Poly (ethylene terephthalate) (PET) has been widely adopted as a scaffold biomaterial, but further hemocompatibility improvement is still needed for wide biomedical applications. Inspired by the composition of adhesive proteins in mussels, we propose to use self-polymerized dopamine to form a surface-adherent polydopamine layer onto PET sheet, followed by Michael addition with N,N-dimethylethylenediamine (DMDA) to build tertiary amine, and final zwitterions(sulfobetaine and carboxybetaine) construction through ring-opening reaction. Physicochemical properties of substrates were demonstrated by water contact angle measurement, attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) and X-ray photoelectron spectroscopy (XPS). The hemocompatibility was evaluated by platelet adhesion, hemolytic, and protein adsorption. The results showed that the zwitterions immobilized PET endowed with improved resistance to nonspecific protein adsorption and platelet adhesion as well as nonhemolytic. The zwitterions with desirable hemocompatibility can be readily tailored to catheter for various biomedical applications. - Highlights: • We first used self-polymerized dopamine to form a thin and surface-adherent polydopamine layer onto PET film. • Then, DMDA was attached to the PET surface by Michael addition. • Sulfobetaine and carboxybetaine were finally constructed through ring-opening reaction. • The modify PET endowed with improved resistance to nonspecific protein adsorption and platelet adhesion.

  9. Zwitterion radicals and anion radicals from electron transfer and solvent condensation with the fingerprint developing agent ninhydrin.

    Science.gov (United States)

    Schertz, T D; Reiter, R C; Stevenson, C D

    2001-11-16

    Ninhydrin (the fingerprint developing agent) spontaneously dehydrates in liquid ammonia and in hexamethylphosphoramide (HMPA) to form indantrione, which has a sufficiently large solution electron affinity to extract an electron from the solvent (HMPA) to produce the indantrione anion radical. In liquid NH(3), the presence of trace amounts of amide ion causes the spontaneous formation of an anion radical condensation product, wherein the no. 2 carbon (originally a carbonyl carbon) becomes substituted with -NH(2) and -OH groups. In HMPA, the indantrione anion radical spontaneously forms condensation products with the HMPA to produce a variety of zwitterionic radicals, wherein the no. 2 carbon becomes directly attached to a nitrogen of the HMPA. The mechanisms for the formation of the zwitterionic paramagnetic condensation products are analogous to that observed in the reaction of ninhydrin with amino acids to yield Ruhemann's Purple, the contrast product in fingerprint development. The formation of anion and zwitterionic radical condensation products from ninhydrin and nitrogen-containing solvents may represent an example of a host of analogous polyketone-solvent reactions.

  10. Using temperature-responsive zwitterionic surfactant to enhance the enzymatic hydrolysis of lignocelluloses and recover cellulase by cooling.

    Science.gov (United States)

    Cai, Cheng; Pang, Yuxia; Zhan, Xuejuan; Zeng, Meijun; Lou, Hongming; Qian, Yong; Yang, Dongjie; Qiu, Xueqing

    2017-11-01

    Some zwitterionic surfactants exhibit upper critical solution temperature (UCST) in aqueous solutions. For the zwitterionic surfactant solution mixed with cellulase, when its temperature is below UCST, the cellulase can be recovered by coprecipitation with zwitterionic surfactant. In this work, 3-(Hexadecyldimethylammonio) propanesulfonate (SB3-16) was selected to enhance the enzymatic hydrolysis of lignocelluloses and recover the cellulase. After adding 2mmol/L of SB3-16, the enzymatic digestibility of eucalyptus pretreated by dilute acid (Eu-DA) and by sulfite (Eu-SPORL) increased from 27.9% and 35.1% to 72.6% and 89.7%, respectively. The results showed that SB3-16 could reduce the non-productive adsorption of cellulase on hydrophobic interface, while it did not significantly inhibit the activity of cellulase. For the solution contained 1wt% SB3-16 and 200mg protein/L CTec2 cellulase, 55.2% of protein could be recovered by cooling. The filter paper activity of the recovered cellulase was 1.93FPU/mg protein, which was 95.8% of its initial activity. Copyright © 2017. Published by Elsevier Ltd.

  11. Cooperative Effects of Zwitterionic-Ionic Surfactant Mixtures on the Interfacial Water Structure Revealed by Sum Frequency Generation Vibrational Spectroscopy.

    Science.gov (United States)

    Pan, Xuecong; Yang, Fangyuan; Chen, Shunli; Zhu, Xuefeng; Wang, Chuanyi

    2018-05-08

    Cooperative effects of a series of equimolar binary zwitterionic-ionic surfactant mixtures on the interfacial water structure at the air-water interfaces have been studied by sum frequency generation vibrational spectroscopy (SFG-VS). For zwitterionic surfactant palmityl sulfobetaine (SNC 16 ), anionic surfactant sodium hexadecyl sulfate (SHS), and cationic surfactant cetyltrimethylammonium bromide (CTAB) with the same length of alkyl chain, significantly enhanced ordering of interfacial water molecules was observed for the zwitterionic-anionic surfactant mixtures SNC 16 -SHS, indicating that SNC 16 interacts more strongly with SHS than with CTAB because of the strong headgroup-headgroup electrostatic attraction for SNC 16 -SHS. Meanwhile, the SFG amplitude ratio of methyl and methylene symmetric stretching modes was used to verify the stronger interaction between SNC 16 and SHS. The conformational order indicator increased from 0.64 for SNC 16 to 7.17 for SNC 16 -SHS but only 0.94 for SNC 16 -CTAB. In addition, another anionic surfactant sodium dodecyl sulfate (SDS) was introduced to study the influence of chain-chain interaction. Decreased SFG amplitude of interfacial water molecules for SNC 16 -SDS was observed. Therefore, both the headgroup-headgroup electrostatic interaction and chain-chain van der Waals attractive interaction of the surfactants play an important role in enhancing the ordering of interfacial water molecules. The results provided experimental and theoretical bases for practical applications of the surfactants.

  12. Corrosion inhibition of iota-carrageenan natural polymer on aluminum in presence of zwitterion mediator in HCl media

    International Nuclear Information System (INIS)

    Fares, Mohammad M.; Maayta, A.K.; Al-Mustafa, Jamil A.

    2012-01-01

    Highlights: ► Inhibition of Al by ι-carrageenan in the presence of zwitterion mediator was investigated. ► Considerable improvement in inhibition efficiency observed in the presence of zwitterion mediator. ► Coherent physical adsorption layer was evidenced by kinetic and thermodynamic parameters. ► Small but consistent fractured island layers observed after acid exposure as revealed by SEM images. - Abstract: ι-Carrageenan a natural polymer has been used as corrosion inhibitor of aluminum in presence of pefloxacin mesylate, acting as zwitterionic mediator, in acidic medium. Considerable improvement in inhibition efficiency occurred in the presence of the mediator. Activation energy of corrosion and other thermodynamic parameters such as standard free energy, standard enthalpy, and standard entropy of the adsorption process revealed better and well-ordered physical adsorption layers in presence of pefloxacin. Adsorption isotherms in absence or presence of pefloxacin mediator appropriately fit in the Langmuir isotherms. The scanning electron microscope (SEM) images demonstrated smooth, glossy, and relatively coherent adsorption layers of the inhibitor on the metal surface in aqueous solution. After the exposure to 2.0 M HCl for 2 h, a smaller but consistent regular shaped fractured layer is obtained.

  13. Hemocompatible control of sulfobetaine-grafted polypropylene fibrous membranes in human whole blood via plasma-induced surface zwitterionization.

    Science.gov (United States)

    Chen, Sheng-Han; Chang, Yung; Lee, Kueir-Rarn; Wei, Ta-Chin; Higuchi, Akon; Ho, Feng-Ming; Tsou, Chia-Chun; Ho, Hsin-Tsung; Lai, Juin-Yih

    2012-12-21

    In this work, the hemocompatibility of zwitterionic polypropylene (PP) fibrous membranes with varying grafting coverage of poly(sulfobetaine methacrylate) (PSBMA) via plasma-induced surface polymerization was studied. Charge neutrality of PSBMA-grafted layers on PP membrane surfaces was controlled by the low-pressure and atmospheric plasma treatment in this study. The effects of grafting composition, surface hydrophilicity, and hydration capability on blood compatibility of the membranes were determined. Protein adsorption onto the different PSBMA-grafted PP membranes from human fibrinogen solutions was measured by enzyme-linked immunosorbent assay (ELISA) with monoclonal antibodies. Blood platelet adhesion and plasma clotting time measurements from a recalcified platelet-rich plasma solution were used to determine if platelet activation depends on the charge bias of the grafted PSBMA layer. The charge bias of PSBMA layer deviated from the electrical balance of positively and negatively charged moieties can be well-controlled via atmospheric plasma-induced interfacial zwitterionization and was further tested with human whole blood. The optimized PSBMA surface graft layer in overall charge neutrality has a high hydration capability and keeps its original blood-inert property of antifouling, anticoagulant, and antithrmbogenic activities when it comes into contact with human blood. This work suggests that the hemocompatible nature of grafted PSBMA polymers by controlling grafting quality via atmospheric plasma treatment gives a great potential in the surface zwitterionization of hydrophobic membranes for use in human whole blood.

  14. Self-assembly of star micelle into vesicle in solvents of variable quality: the star micelle retains its core-shell nanostructure in the vesicle.

    Science.gov (United States)

    Liu, Nijuan; He, Qun; Bu, Weifeng

    2015-03-03

    Intra- and intermolecular interactions of star polymers in dilute solutions are of fundamental importance for both theoretical interest and hierarchical self-assembly into functional nanostructures. Here, star micelles with a polystyrene corona and a small ionic core bearing platinum(II) complexes have been regarded as a model of star polymers to mimic their intra- and interstar interactions and self-assembled behaviors in solvents of weakening quality. In the chloroform/methanol mixture solvents, the star micelles can self-assemble to form vesicles, in which the star micelles shrink significantly and are homogeneously distributed on the vesicle surface. Unlike the morphological evolution of conventional amphiphiles from micellar to vesicular, during which the amphiphilic molecules are commonly reorganized, the star micelles still retain their core-shell nanostructures in the vesicles and the coronal chains of the star micelle between the ionic cores are fully interpenetrated.

  15. Mixed micelles of 7,12-dioxolithocholic acid and selected hydrophobic bile acids: interaction parameter, partition coefficient of nitrazepam and mixed micelles haemolytic potential.

    Science.gov (United States)

    Poša, Mihalj; Tepavčević, Vesna

    2011-09-01

    The formation of mixed micelles built of 7,12-dioxolithocholic and the following hydrophobic bile acids was examined by conductometric method: cholic (C), deoxycholic (D), chenodeoxycholic (CD), 12-oxolithocholic (12-oxoL), 7-oxolithocholic (7-oxoL), ursodeoxycholic (UD) and hiodeoxycholic (HD). Interaction parameter (β) in the studied binary mixed micelles had negative value, suggesting synergism between micelle building units. Based on β value, the hydrophobic bile acids formed two groups: group I (C, D and CD) and group II (12-oxoL, 7-oxoL, UD and HD). Bile acids from group II had more negative β values than bile acids from group I. Also, bile acids from group II formed intermolecular hydrogen bonds in aggregates with both smaller (2) and higher (4) aggregation numbers, according to the analysis of their stereochemical (conformational) structures and possible structures of mixed micelles built of these bile acids and 7,12-dioxolithocholic acid. Haemolytic potential and partition coefficient of nitrazepam were higher in mixed micelles built of the more hydrophobic bile acids (C, D, CD) and 7,12-dioxolithocholic acid than in micelles built only of 7,12-dioxolithocholic acid. On the other hand, these mixed micelles still had lower values of haemolytic potential than micelles built of C, D or CD. The mixed micelles that included bile acids: 12-oxoL, 7-oxoL, UD or HD did not significantly differ from the micelles of 7,12-dioxolithocholic acid, observing the values of their haemolytic potential. Copyright © 2011 Elsevier B.V. All rights reserved.

  16. Interactions between tea catechins and casein micelles and their impact on renneting functionality.

    Science.gov (United States)

    Haratifar, Sanaz; Corredig, Milena

    2014-01-15

    Many studies have shown that tea catechins bind to milk proteins. This research focused on the association of tea polyphenols with casein micelles, and the consequences of the interactions on the renneting behaviour of skim milk. It was hypothesized that epigallocatechin-gallate (EGCG), the main catechin present in green tea, forms complexes with the casein micelles and that the association modifies the processing functionality of casein micelles. The binding of EGCG to casein micelles was quantified using HPLC. The formation of catechin-casein micelles complexes affected the rennet induced gelation of milk, and the effect was concentration dependent. Both the primary as well as the secondary stage of gelation were affected. These experiments clearly identify the need for a better understanding of the effect of tea polyphenols on the processing functionality of casein micelles, before milk products can be used as an appropriate platform for delivery of bioactive compounds. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Engineering single-polymer micelle shape using nonuniform spontaneous surface curvature

    Science.gov (United States)

    Moths, Brian; Witten, T. A.

    2018-03-01

    Conventional micelles, composed of simple amphiphiles, exhibit only a few standard morphologies, each characterized by its mean surface curvature set by the amphiphiles. Here we demonstrate a rational design scheme to construct micelles of more general shape from polymeric amphiphiles. We replace the many amphiphiles of a conventional micelle by a single flexible, linear, block copolymer chain containing two incompatible species arranged in multiple alternating segments. With suitable segment lengths, the chain exhibits a condensed spherical configuration in solution, similar to conventional micelles. Our design scheme posits that further shapes are attained by altering the segment lengths. As a first study of the power of this scheme, we demonstrate the capacity to produce long-lived micelles of horseshoe form using conventional bead-spring simulations in two dimensions. Modest changes in the segment lengths produce smooth changes in the micelle's shape and stability.

  18. The fabrication of nanopatterns with Au nanoparticles-embedded micelles via nanoimprint lithography

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jung-Pil; Kim, Eun-Uk; Koh, Haeng-Deog; Kang, Nam-Goo; Jung, Gun-Young; Lee, Jae-Suk, E-mail: gyjung@gist.ac.k, E-mail: jslee@gist.ac.k [Department of Materials Science and Engineering, Gwangju Institute of Science and Technology (GIST), 261 Cheomdan-gwagiro (Oryong-dong), Buk-gu Gwangju 500-712 (Korea, Republic of)

    2009-09-09

    We fabricated nanopatterns with Au nanoparticles-embedded micelles (Au-micelles) by self-assembly of block copolymers via nanoimprint lithography. The micelle structure prepared by self-assembled block copolymers was used as a template for the synthesis of Au nanoparticles (Au NPs). Au NPs were synthesized in situ inside the micelles of polystyrene-block-poly(2-vinylpyridine) (PS- b-P2VP). Au-micelles were arranged on the trenches of the polymer template, which was imprinted by nanoimprint lithography. The fabrication of line-type and dot-type nanopatterns was carried out by the combined method. In addition, multilayer nanopatterns of the Au-micelles were also proposed.

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

    DEFF Research Database (Denmark)

    Jensen, Andreas Tue Ingemann

    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......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......‐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 glycerolipid and a cholesteryl ether were synthesized with free primary alcohols and a series of their sulphonates (Ms, Ts, Tf) were...

  20. The development of phytosterol-lecithin mixed micelles and organogels.

    Science.gov (United States)

    Matheson, Andrew B; Dalkas, Georgios; Gromov, Andrei; Euston, Stephen R; Clegg, Paul S

    2017-12-13

    We demonstrate that by mixing the phytosterol-ester oryzanol with lecithin in an organic solvent, both components may be dispersed at much higher concentrations than they may be individually. Dynamic light scattering and molecular dynamics simulations show that the mechanism for this is the formation of r ∼ 4 nm mixed micelles. Infrared spectroscopy and simulations suggest that these micelles are formed due in part to hydrogen bonding of the phosphate of the lecithin head-group, and the phenol group of the oryzanol. Rheology shows that by mixing these materials at an equimolar ratio, highly viscous suspensions are created. Furthermore, by adding water to these samples, a solid-like gel may be formed which offers mechanical properties close to those desired for a margarine type spread, whilst still solubilizing the oryzanol.

  1. Application of polymeric nanoparticles and micelles in insulin oral delivery

    Directory of Open Access Journals (Sweden)

    Milind Sadashiv Alai

    2015-09-01

    Full Text Available Diabetes mellitus is an endocrine disease in which the pancreas does not produce sufficient insulin or the body cannot effectively use the insulin it produces. Insulin therapy has been the best choice for the clinical management of diabetes mellitus. The current insulin therapy is via subcutaneous injection, which often fails to mimic the glucose homeostasis that occurs in normal individuals. This provokes numerous attempts to develop a safe and effective noninvasive route for insulin delivery. Oral delivery is the most convenient administration route. However, insulin cannot be well absorbed orally because of its rapid enzymatic degradation in the gastrointestinal tract. Therefore, nanoparticulate carriers such as polymeric nanoparticles and micelles are employed for the oral delivery of insulin. These nanocarriers protect insulin from degradation and facilitate insulin uptake via a transcellular and/or paracellular pathway. This review article focuses on the application of nanoparticles and micelles in insulin oral delivery. The recent advances in this topic are also reviewed.

  2. Micelle-stabilized room-temperature phosphorescence with synchronous scanning

    International Nuclear Information System (INIS)

    Femia, R.A.; Love, L.J.C.

    1984-01-01

    The experimental requirements for synchronous wavelength scanning micelle-stabilized room temperature phosphorescence and the factors affecting peak resolution are presented and compared with those for synchronous wavelength scanning fluorescence. Identification of individual compounds in a four-component mixture is illustrated, and criteria to identify and minimize triplet state energy transfer are given. Considerable improvement in resolution of the synchronous peaks is obtained via second derivative spectra. 20 references, 7 figures, 2 tables

  3. Block copolymer micelles as switchable templates for nanofabrication

    OpenAIRE

    Krishnamoorthy, S; Pugin, R; Brugger, J; Heinzelmann, H; Hoogerwerf, A C; Hinderling, C

    2006-01-01

    Block copolymer inverse micelles from polystyrene-block-poly-2-vinylpyridine (PS-b-P2VP) deposited as monolayer films onto surfaces show responsive behavior and are reversibly switchable between two states of different topography and surface chemistry. The as-coated films are in the form of arrays of nanoscale bumps, which can be transformed into arrays of nanoscale holes by switching through exposure to methanol. The use of these micellar films to act as switchable etch masks for the structu...

  4. Liquid crystalline states of surfactant solutions of isotropic micelles

    International Nuclear Information System (INIS)

    Bagdassarian, C.; Gelbart, W.M.; Ben-Shaul, A.

    1988-01-01

    We consider micellar solutions whose surfactant molecules prefer strongly to form small, globular aggregates in the absence of intermicellar interactions. At sufficiently high volume fraction of surfactant, the isotropic phase of essentially spherical micelles is shown to be unstable with respect to an orientationally ordered (nematic) state of rodlike aggregates. This behavior is relevant to the phase diagrams reported for important classes of aqueous amphiphilic solutions

  5. In vitro evaluation of antioxidant and neuroprotective effects of curcumin loaded in Pluronic micelles

    OpenAIRE

    Cvetelina Gorinova; Denitsa Aluani; Yordan Yordanov; Magdalena Kondeva-Burdina; Virginia Tzankova; Cvetelina Popova; Krassimira Yoncheva

    2016-01-01

    Curcumin is a polyphenolic substance with attractive pharmacological activities (e.g. antioxidant, anti-inflammatory, anticancer). Incorporation of curcumin in polymeric micelles could overcome the problems associated with its instability and low aqueous solubility. The aim of this study was to load curcumin in polymeric micelles based on Pluronic® P 123 or Pluronic® F 127 triblock copolymers and evaluate the antioxidant and neuroprotective effects after micellization. The micelles were prepa...

  6. Gadolinium DTPA-monoamide complexes incorporated into mixed micelles as possible MRI contrast agents

    OpenAIRE

    Parac-Vogt, Tatjana; Kimpe, Kristof; Laurent, Sophie; Pierart, Corinne; Vander Elst, Luce; Muller, Robert N.; Binnemans, Koen

    2004-01-01

    Four monoamide derivatives of Gd-DTPA with alkyl chains consisting of 12, 14, 16, or 18 carbon atoms were synthesized. The gadolinium(III) complexes with chain lengths of 14, 16 or 18 carbon atoms were efficiently incorporated into mixed micelles whereas the complex with a chain length of 12 carbon atoms was not incorporated into a micellar structure. The size distribution of the micelles was measured by photon correlation spectroscopy. The mean sizes of the micelles for all the complexes lay...

  7. 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.

  8. Predicting proton titration in cationic micelle and bilayer environments

    Science.gov (United States)

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

    2014-08-01

    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 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.

  9. Complexation of Polyelectrolyte Micelles with Oppositely Charged Linear Chains.

    Science.gov (United States)

    Kalogirou, Andreas; Gergidis, Leonidas N; Miliou, Kalliopi; Vlahos, Costas

    2017-03-02

    The formation of interpolyelectrolyte complexes (IPECs) from linear AB diblock copolymer precursor micelles and oppositely charged linear homopolymers is studied by means of molecular dynamics simulations. All beads of the linear polyelectrolyte (C) are charged with elementary quenched charge +1e, whereas in the diblock copolymer only the solvophilic (A) type beads have quenched charge -1e. For the same Bjerrum length, the ratio of positive to negative charges, Z +/- , of the mixture and the relative length of charged moieties r determine the size of IPECs. We found a nonmonotonic variation of the size of the IPECs with Z +/- . For small Z +/- values, the IPECs retain the size of the precursor micelle, whereas at larger Z +/- values the IPECs decrease in size due to the contraction of the corona and then increase as the aggregation number of the micelle increases. The minimum size of the IPECs is obtained at lower Z +/- values when the length of the hydrophilic block of the linear diblock copolymer decreases. The aforementioned findings are in agreement with experimental results. At a smaller Bjerrum length, we obtain the same trends but at even smaller Z +/- values. The linear homopolymer charged units are distributed throughout the corona.

  10. Nanoparticle Contrast Agents for Computed Tomography: A Focus on Micelles

    Science.gov (United States)

    Cormode, David P.; Naha, Pratap C.; Fayad, Zahi A.

    2014-01-01

    Computed tomography (CT) is an X-ray based whole body imaging technique that is widely used in medicine. Clinically approved contrast agents for CT are iodinated small molecules or barium suspensions. Over the past seven years there has been a great increase in the development of nanoparticles as CT contrast agents. Nanoparticles have several advantages over small molecule CT contrast agents, such as long blood-pool residence times, and the potential for cell tracking and targeted imaging applications. Furthermore, there is a need for novel CT contrast agents, due to the growing population of renally impaired patients and patients hypersensitive to iodinated contrast. Micelles and lipoproteins, a micelle-related class of nanoparticle, have notably been adapted as CT contrast agents. In this review we discuss the principles of CT image formation and the generation of CT contrast. We discuss the progress in developing non-targeted, targeted and cell tracking nanoparticle CT contrast agents. We feature agents based on micelles and used in conjunction with spectral CT. The large contrast agent doses needed will necessitate careful toxicology studies prior to clinical translation. However, the field has seen tremendous advances in the past decade and we expect many more advances to come in the next decade. PMID:24470293

  11. Negative adsorption due to electrostatic exclusion of micelles.

    Science.gov (United States)

    Somasundaran, P; Ananthapadmanabhan, K P; Deo, Puspendu

    2005-10-15

    Interactions of surfactants with solid substrates are important in the controlling of processes such as flotation, coating, flocculation and sedimentation. These interactions usually lead to adsorption on solids, but can also result in an exclusion of the reagents with dire consequences. In this work electrostatic exclusion of negatively charged dodecylbenzene sulfonate micelles from quartz/water, Bio-Sil/water and alumina/water interfaces has been investigated as a function of pH and ionic strength. Measurable negative adsorption of these surfactants from similarly charged solid/liquid interface was observed in the micellar region. In the case of porous samples with large surface area, comparison of pore size with the micelle size is necessary to avoid any erroneous conclusions regarding the role of electrostatic exclusion in a given system. A theoretical model for the electrostatic exclusion of micelles is developed and used to calculate the adsorption of negatively charged dodecylbenzene sulfonate on negatively charged quartz (pH 7), silica (Bio-Sil A, pH 3) and alumina (pH 11) in the micellar concentration region. The micellar exclusion values calculated using the model are in excellent agreement with the experimental results.

  12. 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.

  13. Relationship between structure and reactivity in AOT inverse micelles

    International Nuclear Information System (INIS)

    Petit, Christophe

    1988-01-01

    As inverse micelles can be considered as chemical micro-reactors, the objective of this research thesis is to show that reaction rates can be modified, either by varying the size of micro-reactors, or by modifying the location of one of the reactants. After a brief overview of noticeable results obtained on AOT inverse micelles about the structure and reactivity, the author reports the study of structural modifications induced by an addition of small molecules or proteins. Two complementary models are proposed on this purpose: a geometrical model which reports the medium microscopic evolution and a kinetic model which could report the system microscopic evolution as well reactivity changes with respect to probe location. The next part reports the study of in situ synthesis of semi-conductor particles in AOT inverse micelles. The author then reports that a surprising aspect of macromolecule solubilization has been noticed: the solubilization of a polypeptide, gelatine, allows the whole system to be gelled whereas gelatine is essentially polar [fr

  14. Synthesis of star-branched PLA-b-PMPC copolymer micelles as long blood circulation vectors to enhance tumor-targeted delivery of hydrophobic drugs in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Long, Li-xia [Tianjin Key Laboratory of Composite and Functional Materials, School of Materials Science & Engineering, Tianjin University, Tianjin 300072 (China); Zhao, Jin, E-mail: zhaojin@tju.edu.cn [Tianjin Key Laboratory of Composite and Functional Materials, School of Materials Science & Engineering, Tianjin University, Tianjin 300072 (China); Li, Ke; He, Li-gang; Qian, Xiao-ming; Liu, Chao-yong; Wang, Li-mei; Yang, Xin-qi [Tianjin Key Laboratory of Composite and Functional Materials, School of Materials Science & Engineering, Tianjin University, Tianjin 300072 (China); Sun, Jinjin [Department of General Surgery, The Second Hospital of Tianjin Medical University, Tianjin 300211 (China); Ren, Yu [Tianjin Research Center of Basic Medical Science, Tianjin Medical University, Tianjin 300070 (China); Kang, Chun-sheng, E-mail: kang97061@yahoo.com [Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052 (China); Yuan, Xu-bo, E-mail: xbyuan@tju.edu.cn [Tianjin Key Laboratory of Composite and Functional Materials, School of Materials Science & Engineering, Tianjin University, Tianjin 300072 (China)

    2016-09-01

    Star-branched amphiphilic copolymer nanocarriers with high-density zwitterionic shell show great promise in drug delivery due to their controllable small size and excellent anti-biofouling properties. This gives the hydrophobic cargo with high stability and long blood circulation in vivo. In the present study, star-branched polylactic acid and poly(2-methacryloyloxyethyl phosphorylcholine) copolymers with (AB{sub 3}){sub 3}–type architecture (PLA-b-PMPC{sub 3}){sub 3} were conceived as drug vectors, and the copolymers were synthesized by an “arm-first” approach via the combination of ring opening polymerization (ROP), atom transfer radical polymerization (ATRP) and the click reaction. The self-assembled star-branched copolymer micelles (sCPM) had an average diameter of about 64.5 nm and exhibited an ultra-hydrophilic surface with an ultralow water contact angle of about 12.7°, which efficiently suppressed the adhesion of serum proteins. In vivo experiments showed that the sCPM loading strongly enhanced the blood circulation time of DiI and the plasma half-life of DiI in sCPM was 19.3 h. The relative accumulation concentration in tumor of DiI delivered by sCPM was 2.37-fold higher than that of PLA-PEG, at 4 h after intravenous injection. These results demonstrated that the star-branched copolymer (PLA-b-PMPC{sub 3}){sub 3} is a promising alternative carrier material for intravenous delivery versus classic PEG-modified strategies. - Highlights: • Star-branched amphiphilic copolymer micelles (sCPM) with zwitterionic shells were prepared. • sCPM possess an ultra-hydrophilic surface and thus inhibited the protein absorption. • sCPM can effectively prolong the cargo’s plasma circulation time. • sCPM can enhance the cargo’s passive tumor-targeted delivery.

  15. 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.

  16. Effect of Urea on the Thermodynamics of Hexadecyltrimethylammonium Bromide Micelle Formation in Aqueous Solutions

    Science.gov (United States)

    Velikov, A. A.

    2018-02-01

    The effect of urea on the thermodynamics of hexadecyltrimethylammonium bromide (CTAB) micelle formation in aqueous urea solutions was studied by isothermal titration microcalorimetry. The thermodynamic functions of Δ H, Δ G, and Δ S of CTAB micelle formation were calculated. The critical micelle concentrations (CMC) were determined. The addition of urea to the solution decreased the micelle formation entropy. This was attributed to the "lowering" of the structural temperature of the solution, which led to an increased number of hydrogen bonds and structure formation of water.

  17. Hydrolytic degradation of poly(ethylene oxide)-block-polycaprolactone worm micelles.

    Science.gov (United States)

    Geng, Yan; Discher, Dennis E

    2005-09-21

    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 polycaprolactone hydrolysis, with distinct mechanism and kinetics from that which occurs in bulk material.

  18. Small angle neutron scattering study of the micelle structure of amphiphilic block copolymers

    International Nuclear Information System (INIS)

    Yamaoka, H.; Matsuoka, H.; Sumaru, K.; Hanada, S.

    1994-01-01

    The amphiphilic block copolymers of vinyl ether were prepared by living cationic polymerization. The partially deuterated copolymers for SANS experiments were especially synthesized by introducing deuterated phenyl units in the hydrophobic chain. SANS measurements were performed for aqueous solutions of these copolymers by changing H 2 O/D 2 O ratios. The SANS profiles indicate that the micelles in the present system exhibit a core-shell structure and that the size and shape of micelles are largely dependent on the length of hydrophobic chain. The micelle of shorter hydrophobic chain was found to be nearly spherical, whereas the micelle of longer hydrophobic chain was confirmed to have an ellipsoidal shape

  19. 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.

  20. Building a Better Microreactor: Enzyme Catalysis in AOT/Bile Salt Reversed Micelles

    National Research Council Canada - National Science Library

    McGown, Linda

    2001-01-01

    .... We have shown that trihydroxy bile salts modify the interfacial properties of AOT reversed micelles, thereby affecting the reversed micellar structure, the biological activity of entrapped enzymes...

  1. 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.

  2. Quantum mechanical effects in zwitterionic amino acids: The case of proline, hydroxyproline, and alanine in water

    Science.gov (United States)

    Ulman, Kanchan; Busch, Sebastian; Hassanali, Ali A.

    2018-06-01

    In this work, we use ab initio molecular dynamics simulations to elucidate the electronic properties of three hydrated zwitterionic amino acids, namely proline, hydroxyproline, and alanine, the former two forming an important constituent of collagen. In all three systems, we find a substantial amount of charge transfer between the amino acids and surrounding solvent, which, rather surprisingly, also involves the reorganization of electron density near the hydrophobic non-polar groups. Water around proline appears to be slightly more polarized, as reflected by the enhanced water dipole moment in its hydration shell. This observation is also complemented by an examination of the IR spectra of the three systems where there is a subtle red and blue shift in the O-H stretch and bend regions, respectively, for proline. We show that polarizability of these amino acids as revealed by a dipole moment analysis involves a significant enhancement from the solvent and that this also involves non-polar groups. Our results suggest that quantum mechanical effects are likely to be important in understanding the coupling between biomolecules and water in general and in hydrophobic interactions.

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

    International Nuclear Information System (INIS)

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

    2012-01-01

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

  4. Crosslinked copolyazoles with a zwitterionic structure for organic solvent resistant membranes

    KAUST Repository

    Chisca, Stefan

    2015-01-01

    The preparation of crosslinked membranes with a zwitterionic structure based on a facile reaction between a newly synthesized copolyazole with free OH groups and (3-glycidyloxypropyl)trimethoxysilane (GPTMS) is reported. The new OH-functionalized copolyazole is soluble in common organic solvents, such as tetrahydrofuran (THF), dimethylsulfoxide (DMSO), N,N′-dimethylformamide (DMF) and N-methyl-2-pyrrolidone (NMP) and can be easily processed by phase inversion. After crosslinking with GPTMS, the membranes acquire high solvent resistance. We show the membrane performance and the influence of the crosslinking reaction conditions on the thermal stability, surface polarity, pore morphology, and solvent resistance. By using UV-spectroscopy we monitored the solvent resistance of the membranes in four aggressive solvents (THF, DMSO, DMF and NMP) for 30 days. After this time, only minor changes (less than 2%) were detected for membranes subjected to a crosslinking reaction for 6 hours or longer. Our data suggest that the novel crosslinked membranes can be used for industrial applications in wide harsh environments in the presence of organic solvents.

  5. Simple Protein Modification Using Zwitterionic Polymer to Mitigate the Bioactivity Loss of Conjugated Insulin.

    Science.gov (United States)

    Xie, Jinbing; Lu, Yang; Wang, Wei; Zhu, Hui; Wang, Zhigang; Cao, Zhiqiang

    2017-06-01

    Polymer-protein conjugation has been extensively explored toward a better protein drug with improved pharmacokinetics. However, a major problem with polymer-protein conjugation is that the polymers drastically reduce the bioactivity of the modified protein. There is no perfect solution to prevent the bioactivity loss, no matter the polymer is conjugated in a non-site specific way, or a more complex site-specific procedure. Here the authors report for the first time that when zwitterionic carboxybetaine polymer (PCB) is conjugated to insulin through simple conventional coupling chemistry. The resulting PCB-insulin does not show a significant reduction of in vitro bioactivity. The obtained PCB-insulin shows two significant advantages as a novel pharmaceutical agent. First, its therapeutic performance is remarkable. For PCB-insulin, there is a 24% increase of in vivo pharmacological activity of lowering blood glucose compared with native insulin. Such uncommonly seen increase has rarely been reported and is expected to be due to both the improved pharmacokinetics and retained bioactivity of PCB-insulin. Second, the production is simple from manufacturing standpoints. Conjugation procedure involves only one-step coupling reaction without complex site-specific linkage technique. The synthesized PCB-insulin conjugates do not require chromatographic separation to purify and obtain particular isoforms. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Macrocyclic Gd(3+) complexes with pendant crown ethers designed for binding zwitterionic neurotransmitters.

    Science.gov (United States)

    Oukhatar, Fatima; Meudal, Hervé; Landon, Céline; Logothetis, Nikos K; Platas-Iglesias, Carlos; Angelovski, Goran; Tóth, Éva

    2015-07-27

    A series of Gd(3+) complexes exhibiting a relaxometric response to zwitterionic amino acid neurotransmitters was synthesized. The design concept involves ditopic interactions 1) between a positively charged and coordinatively unsaturated Gd(3+) chelate and the carboxylate group of the neurotransmitters and 2) between an azacrown ether appended to the chelate and the amino group of the neurotransmitters. The chelates differ in the nature and length of the linker connecting the cyclen-type macrocycle that binds the Ln(3+) ion and the crown ether. The complexes are monohydrated, but they exhibit high proton relaxivities (up to 7.7 mM(-1)  s(-1) at 60 MHz, 310 K) due to slow molecular tumbling. The formation of ternary complexes with neurotransmitters was monitored by (1) H relaxometric titrations of the Gd(3+) complexes and by luminescence measurements on the Eu(3+) and Tb(3+) analogues at pH 7.4. The remarkable relaxivity decrease (≈80 %) observed on neurotransmitter binding is related to the decrease in the hydration number, as evidenced by luminescence lifetime measurements on the Eu(3+) complexes. These complexes show affinity for amino acid neurotransmitters in the millimolar range, which can be suited to imaging concentrations of synaptically released neurotransmitters. They display good selectivity over non-amino acid neurotransmitters (acetylcholine, serotonin, and noradrenaline) and hydrogenphosphate, but selectivity over hydrogencarbonate was not achieved. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Creation of antifouling microarrays by photopolymerization of zwitterionic compounds for protein assay and cell patterning.

    Science.gov (United States)

    Sun, Xiuhua; Wang, Huaixin; Wang, Yuanyuan; Gui, Taijiang; Wang, Ke; Gao, Changlu

    2018-04-15

    Nonspecific binding or adsorption of biomolecules presents as a major obstacle to higher sensitivity, specificity and reproducibility in microarray technology. We report herein a method to fabricate antifouling microarray via photopolymerization of biomimetic betaine compounds. In brief, carboxybetaine methacrylate was polymerized as arrays for protein sensing, while sulfobetaine methacrylate was polymerized as background. With the abundant carboxyl groups on array surfaces and zwitterionic polymers on the entire surfaces, this microarray allows biomolecular immobilization and recognition with low nonspecific interactions due to its antifouling property. Therefore, low concentration of target molecules can be captured and detected by this microarray. It was proved that a concentration of 10ngmL -1 bovine serum albumin in the sample matrix of bovine serum can be detected by the microarray derivatized with anti-bovine serum albumin. Moreover, with proper hydrophilic-hydrophobic designs, this approach can be applied to fabricate surface-tension droplet arrays, which allows surface-directed cell adhesion and growth. These light controllable approaches constitute a clear improvement in the design of antifouling interfaces, which may lead to greater flexibility in the development of interfacial architectures and wider application in blood contact microdevices. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Exploration of zwitterionic cellulose acetate antifouling ultrafiltration membrane for bovine serum albumin (BSA) separation.

    Science.gov (United States)

    Liu, Yang; Huang, Haitao; Huo, Pengfei; Gu, Jiyou

    2017-06-01

    This study focused on the preparation of a new kind of membrane material, zwitterionic cellulose acetate (ZCA), via a three-step procedure consist of oxidization, Schiff base and quaternary amination reaction, and the fabrication of antifouling ZCA ultrafiltration membrane by the non-solvent-induced phase separation method (NIPS). The morphologies, surface chemical structures and compositions of the obtained CA and ZCA membranes were thoroughly characterized by field emission scanning electron microscopy (FE-SEM) with energy dispersive X-ray (EDX) spectroscopy, Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS), respectively. Meanwhile, the thermal stability, porosity and average pore size of two investigated membranes were also studied. As a result, the ZCA membrane displayed significantly improved hydrophilicity and water permeability compared with those of the reference CA membrane, despite a slight decrease in the protein rejection ratio. According to the cycle ultrafiltration performance of bovine serum albumin (BSA) solution and protein adsorption experiment, ZCA membrane exhibited better flux recovery property and fouling resistant ability, especially irreversible fouling resistant ability, suggesting superior antifouling performance. This new approach gives polymer-based membrane a long time life and excellent ultrafiltration performance, and seems promising for potential applications in the protein separation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Preparation and structural characterization of zwitterionic surfactant intercalated into NiZn-layered hydroxide salts

    Science.gov (United States)

    Liu, Jiexiang; Wang, Jianlong; Zhang, Xiaoguang; Fang, Binbin; Hu, Pan; Zhao, Xuyang

    2015-10-01

    Three zwitterionic surfactants, dodecyl dimethyl carboxylbetaine (DCB), dodecyl dimethyl sulfobetaine (DSB) and N-dodecyl-β-aminoprpionate (DAP), intercalated into NiZn-layered hydroxide salts (NZL-DCB, NZL-DSB and NZL-DAP) were synthesized by the coprecipitation method. The effect of surfactant content, pH, temperature and time of hydrothermal treatment on preparation was investigated and discussed. The NZL-DCB, NZL-DSB and NZL-DAP were characterized by powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR), and thermogravimetry analysis and differential thermal analysis (TGA/DTA). The results showed that basal spacings of NZL-DCB, NZL-DSB and NZL-DAP were around 3.45, 3.68 and 3.94 nm, respectively. DCB, DSB and DAP probably form an overlapped bilayer in the gallery. TGA/DTA data indicated that NZL-DCB, NZL-DSB and NZL-DAP displayed three loss weight stages: loss of adsorbed and structural water, dehydroxylation of matrix and decomposition of nitrate ions, decomposition and combustion of surfactants. Furthermore, chemical analysis data, BET surface area and scanning electron microscopic (SEM) were also measured and analyzed.

  10. Zwitterionization of glycine in water environment: Stabilization mechanism and NMR spectral signatures

    Science.gov (United States)

    Valverde, Danillo; da Costa Ludwig, Zélia Maria; da Costa, Célia Regina; Ludwig, Valdemir; Georg, Herbert C.

    2018-01-01

    At physiological conditions, myriads of biomolecules (e.g., amino acids, peptides, and proteins) exist predominantly in the zwitterionic structural form and their biological functions will result in these conditions. However these geometrical structures are inaccessible energetically in the gas phase, and at this point, stabilization of amino-acids in physiological conditions is still under debate. In this paper, the electronic properties of a glycine molecule in the liquid environment were studied by performing a relaxation of the glycine geometry in liquid water using the free energy gradient method combined with a sequential quantum mechanics/molecular mechanics approach. A series of Monte Carlo Metropolis simulations of the glycine molecule embedded in liquid water, followed by only a quantum mechanical calculation in each of them were carried out. Both the local and global liquid environments were emphasized to obtain nuclear magnetic resonance (NMR) parameters for the glycine molecule in liquid water. The results of the equilibrium structure in solution and the systematic study of the hydrogen bonds were used to discard the direct proton transfer from the carboxyl group to the ammonium group of the glycine molecule in water solution. The calculations of the Density Functional Theory (DFT) were performed to study the polarization of the solvent in the parameters of nuclear magnetic resonance of the glycine molecule in liquid water. DFT calculations predicted isotropic chemical changes on the H, C, N, and O atoms of glycine in liquid water solution which agree with the available experimental data.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-06-15

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

  12. Zwitterionic phosphorylcholine grafted chitosan nanofiber: Preparation, characterization and in-vitro cell adhesion behavior

    Energy Technology Data Exchange (ETDEWEB)

    Oktay, Burcu; Kayaman-Apohan, Nilhan, E-mail: napohan@marmara.edu.tr; Süleymanoğlu, Mediha; Erdem-Kuruca, Serap

    2017-04-01

    In this study, zwitterionic phosphorylcholine grafted electrospun chitosan fiber was accomplished in three steps: (1) Azide groups on the chitosan were regioselectively replaced with hydroxyl side group and then the product was electrospun. (2) Chitosan based macroinitiator was prepared using an azide-alkyne click reaction from azide-functionalized electrospun chitosan fiber. (3) Poly(2-methacryloyloxyethyl phosphorylcholine) (MPC) was grafted onto the electrospun chitosan fiber by atom transfer radical polymerization (ATRP) in order to enhance cellular viability and proliferation of 3T3, ECV and Saos. The structure of surface modified chitosan was characterized by Fourier transform infrared spectrometer (FT-IR) and {sup 1}H nuclear magnetic resonance ({sup 1}H NMR). The surface morphology of the nanofibers was investigated by scanning electron microscope (SEM). In-vitro cellular attachment and spreading experiments of 3T3, ECV304 and Saos were performed on electrospun chitosan fibers in the presence and the absence of MPC grafting. Poly(MPC) grafted electrospun fiber showed an excellent performance due to phosphorylcholine groups mimicking the natural phospholipid. - Highlights: • Chitosan was functionalized in a controlled way. • Poly(MPC) grafted electrospun chitosan fiber was prepared by click and ATRP. • Controlled molecular architecture was achieved. • Cellular attachment and spreading efficiency of the nanofiber were investigated. • These nanofibers have potential applications in tissue engineering with tissue.

  13. Forced Spreading of Aqueous Solutions on Zwitterionic Sulfobetaine Surfaces for Rapid Evaporation and Solute Separation.

    Science.gov (United States)

    Wu, Cyuan-Jhang; Singh, Vickramjeet; Sheng, Yu-Jane; Tsao, Heng-Kwong

    2017-08-01

    Solute separation of aqueous mixtures is mainly dominated by water vaporization. The evaporation rate of an aqueous drop grows with increasing the liquid-gas interfacial area. The spontaneous spreading behavior of a water droplet on a total wetting surface provides huge liquid-gas interfacial area per unit volume; however, it is halted by the self-pinning phenomenon upon addition of nonvolatile solutes. In this work, it is shown that the solute-induced self-pinning can be overcome by gravity, leading to anisotropic spreading much faster than isotropic spreading. The evaporation rate of anisotropic spreading on a zwitterionic sulfobetaine surface is 25 times larger as that on a poly(methyl methacrylate) surface. Dramatic enhancement of evaporation is demonstrated by simultaneous formation of fog atop liquid film. During anisotropic spreading, the solutes are quickly precipitated out within 30 s, showing the rapid solute-water separation. After repeated spreading process for the dye-containing solution, the mean concentration of the collection is doubled, revealing the concentration efficiency as high as 100%. Gravity-enhanced spreading on total wetting surfaces at room temperature is easy to scale-up with less energy consumption, and thus it has great potentials for the applications of solute separation and concentration.

  14. 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.

  15. 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.

  16. 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)

    Cuong, Nguyen-Van; Jiang, Jian-Lin; Li, Yu-Lun; Chen, Jim-Ray; Jwo, Shyh-Chuan; Hsieh, Ming-Fa

    2010-01-01

    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

  17. Micelle-like nanoassemblies based on polymer-drug conjugates as an emerging platform for drug delivery.

    Science.gov (United States)

    Liu, Zhihong; Wang, Yutao; Zhang, Na

    2012-07-01

    During the past decades, polymer-drug conjugates are one of the hottest topics in novel drug development fields. Amphiphilic polymer-drug conjugates in aqueous solution could form micelles or micelle-like nanoassemblies. Compared with polymer-drug conjugates and the micelles into which drugs are physically entrapped, micelles or micelle-like nanoassemblies based on polymer-drug conjugates bring several additional advantages, including increased drug-loading capacity, enhanced intracellular uptake, reduced systemic toxicity, and improved therapeutic efficacy. This review focuses on recent progress achieved in the research field of micelles or micelle-like nanoassemblies based on polymer-drug conjugates. Firstly, properties of polymers, drugs, and linkers which could be used to build polymer-drug conjugate micelles or micelle-like nanoassemblies are summarized. Then, the characterization methods are described. Finally, the drug-targeting mechanisms are discussed. Micelles or micelle-like nanoassemblies based on polymer-drug conjugates as an emerging platform have the potential to achieve medical treatments with enhanced therapeutic effect. The application of micelles or micelle-like nanoassemblies based on polymer-drug conjugates may give new life to old active compounds abandoned due to their low solubility problems. For clinical application, there is a need to further optimize the properties of the polymer, drug, and linker.

  18. Amino Acid Functionalization of Doped Single-Walled Carbon Nanotubes: Effects of Dopants and Side Chains as Well as Zwitterionic Stabilizations.

    Science.gov (United States)

    Jiang, Lisha; Zhu, Chang; Fu, Yujie; Yang, Gang

    2017-04-06

    Functionalization of single-walled carbon nanotubes (SWCNTs) is necessitated in a number of conditions such as drug delivery, and here amino acid functionalization of SWCNTs is conducted within the framework of density functional theory. Functionalization efficiencies of Gly are largely determined by dopants, as a combined effect of atomic radius, electronic configuration, and distortion to SWCNTs. Different functionalization sites in Gly have divergent interaction strengths with M/SWCNTs that decline as O b > N > O a , and this trend seems almost independent of the identity of metallic dopants. B/SWCNT behaves distinctly and prefers to the N site. Dopants affect principally interaction strengths, while amino acids regulate significantly both functionalization configurations and interaction energies. Then focus is given to stabilization of zwitterionic amino acids due to enhanced interactions with the widely used zwitterionic drugs. All metallic dopants render zwitterionic Gly to be the most stable, and side chains in amino acids rather than dopants in M/SWCNTs cause more pronounced effects to zwitterionic stabilizations. Charge transfers between amino acids and M/SWCNTs are closely associated with zwitterionic stabilization effects, and different charge transfer mechanisms between M/SWCNTs and metal ions are interpreted. Thus, this work provides a comprehensive understanding of amino acid functionalization of M/SWCNTs.

  19. Multifunctional theranostic Pluronic mixed micelles improve targeted photoactivity of Verteporfin in cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Silva Pellosi, Diogo [Laboratory of Phobiology and photomdicine, Department of Chemistry (FFCLRP), University of São Paulo, Av. dos Bandeirantes 3900, 14040-901, Vila Monte Alegre, Ribeirão Preto (Brazil); Calori, Italo Rodrigo [Research Nucleus of Photodynamic Therapy, Department of Chemistry, State University of Maringá, Av. Colombo 5790, 97020-900 Maringá (Brazil); Barcelos de Paula, Leonardo [Laboratory of Phobiology and photomdicine, Department of Chemistry (FFCLRP), University of São Paulo, Av. dos Bandeirantes 3900, 14040-901, Vila Monte Alegre, Ribeirão Preto (Brazil); Hioka, Noboru [Research Nucleus of Photodynamic Therapy, Department of Chemistry, State University of Maringá, Av. Colombo 5790, 97020-900 Maringá (Brazil); Quaglia, Fabiana [Laboratory of Drug Delivery, Department of Pharmacy, University of Napoli Federico II, Via Domenico Montesanto 49, 80131 Napoli (Italy); Tedesco, Antonio Claudio, E-mail: atedesco@usp.br [Laboratory of Phobiology and photomdicine, Department of Chemistry (FFCLRP), University of São Paulo, Av. dos Bandeirantes 3900, 14040-901, Vila Monte Alegre, Ribeirão Preto (Brazil)

    2017-02-01

    Nanotechnology development provides new strategies to treat cancer by integration of different treatment modalities in a single multifunctional nanoparticle. In this scenario, we applied the multifunctional Pluronic P123/F127 mixed micelles for Verteporfin-mediated photodynamic therapy in PC3 and MCF-7 cancer cells. Micelles functionalization aimed the targeted delivery by the insertion of biotin moiety on micelle surface and fluorescence image-based through rhodamine-B dye conjugation in the polymer chains. Multifunctional Pluronics formed spherical nanoparticulated micelles that efficiently encapsulated the photosensitizer Verteporfin maintaining its favorable photophysical properties. Lyophilized formulations were stable at least for 6 months and readily reconstituted in aqueous media. The multifunctional micelles were stable in protein-rich media due to the dual Pluronic mixed micelles characteristic: high drug loading capacity provided by its micellar core and high kinetic stability due its biocompatible shell. Biotin surface functionalized micelles showed higher internalization rates due biotin-mediated endocytosis, as demonstrated by competitive cellular uptake studies. Rhodamine B-tagged micelles allowed monitoring cellular uptake and intracellular distribution of the formulations. Confocal microscopy studies demonstrated a larger intracellular distribution of the formulation and photosensitizer, which could drive Verteporfin to act on multiple cell sites. Formulations were not toxic in the dark condition, but showed high Verteporfin-induced phototoxicity against both cancer cell lines at low drug and light doses. These results point Verteporfin-loaded multifunctional micelles as a promising tool to further developments in photodynamic therapy of cancer. - Highlights: • We optimized the theranostic mixed micelles – verteporfin formulations. • Multifunctional Pluronic micelles formed nano-sized spherical nanoparticles. • Biotin surface conjugation

  20. Glutathione-responsive core cross-linked micelles for controlled cabazitaxel delivery

    Science.gov (United States)

    Han, Xiaoxiong; Gong, Feirong; Sun, Jing; Li, Yueqi; Liu, XiaoFei; Chen, Dan; Liu, Jianwen; Shen, Yaling

    2018-02-01

    Stimulus-responsive polymeric micelles (PMs) have recently received attention due to the controlled delivery of drug or gene for application in cancer diagnosis and treatment. In this work, novel glutathione-responsive PMs were prepared to encapsulate hydrophobic antineoplastic drug, cabazitaxel (CTX), to improve its solubility and toxicity. These CTX-loaded micelles core cross-linked by disulfide bonds (DCL-CTX micelles) were prepared by a novel copolymer, lipoic acid grafted mPEG-PLA. These micelles had regular spherical shape, homogeneous diameter of 18.97 ± 0.23 nm, and a narrow size distribution. The DCL-CTX micelles showed high encapsulation efficiency of 98.65 ± 1.77%, and the aqueous solubility of CTX was improved by a factor of 1:1200. In vitro release investigation showed that DCL-CTX micelles were stable in the medium without glutathione (GSH), whereas the micelles had burst CTX release in the medium with 10 mM GSH. Cell uptake results implied that DCL-CTX micelles were internalized into MCF-7 cells through clathrin-mediated endocytosis and released cargo more effectively than Jevtana (commercially available CTX) owing to GSH-stimulated degradation. In MTT assay against MCF-7 cells, these micelles inhibited tumor cell proliferation more effectively than Jevtana due to their GSH-responsive CTX release. All results revealed the potency of GSH-responsive DCL-CTX micelles for stable delivery in blood circulation and for intracellular GSH-trigged release of CTX. Therefore, DCL-CTX micelles show potential as safe and effective CTX delivery carriers and as a cancer chemotherapy formulation.

  1. Reduction-responsive interlayer-crosslinked micelles prepared from star-shaped copolymer via click chemistry for drug controlled release

    Science.gov (United States)

    Dai, Yu; Wang, Hongquan; Zhang, Xiaojin

    2017-12-01

    To improve the stability of polymeric micelles, here we describe interlayer-crosslinked micelles prepared from star-shaped copolymer via click chemistry. The formation of interlayer-crosslinked micelles was investigated and confirmed by proton nuclear magnetic resonance, Fourier-transform infrared spectroscopy, and fluorescence spectroscopy. The morphology of un-crosslinked micelles and crosslinked micelles observed by transmission electron microscope is both uniform nano-sized spheres (approximately 20 nm). The crosslinking enhances the stability of polymeric micelles and improves the drug loading capacity of polymeric micelles. The interlayer-crosslinked micelles prepared from star-shaped copolymer and a crosslinker containing a disulfide bond are reduction-responsive and can release the drug quickly in the presence of the reducing agents such as glutathione (GSH).

  2. A New Approach to Non-Coordinating Anions: Lewis Acid Enhancement of Porphyrin Metal Centers in a Zwitterionic Metal$-$Organic Framework

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, Jacob A. [Univ. of Nebraska, Lincoln, NE (United States). Dept. of Chemistry; Petersen, Brenna M. [Univ. of Nebraska, Lincoln, NE (United States). Dept. of Chemistry; Kormos, Attila [Hungarian Academy of Sciences, Budapest (Hungary); Echeverría, Elena [Univ. of Nebraska, Lincoln, NE (United States). Dept. of Physics and Astronomy; Chen, Yu-Sheng [Univ. of Chicago, Argonne, IL (United States). ChemMatCARS, Center for Advanced Radiation Sources; Zhang, Jian [Univ. of Nebraska, Lincoln, NE (United States). Dept. of Chemistry

    2017-02-28

    Here, we describe a new strategy to generate non-coordinating anions using zwitterionic metal–organic frameworks (MOFs). By assembly of anionic inorganic secondary building blocks (SBUs) ([In(CO2)4]$-$) with cationic metalloporphyrin-based organic linkers, we prepared zwitterionic MOFs in which the complete internal charge separation effectively prevents the potential binding of the counteranion to the cationic metal center. We demonstrate the enhanced Lewis acidity of MnIII- and FeIII-porphyrins in the zwitterionic MOFs in three representative electrocyclization reactions: [2 + 1] cycloisomerization of enynes, [3 + 2] cycloaddition of aziridines and alkenes, and [4 + 2] hetero-Diels–Alder cycloaddition of aldehydes with dienes. Lastly, this work paves a new way to design functional MOFs for tunable chemical catalysis.

  3. Self-association of an indole based guanidinium-carboxylate-zwitterion: formation of stable dimers in solution and the solid state

    Directory of Open Access Journals (Sweden)

    Carolin Rether

    2010-01-01

    Full Text Available The indole based zwitterion 2 forms stable dimers held together by H-bond assisted ion pairs. Dimerisation was confirmed in the solid state and studied in solution using dilution NMR experiments. Even though zwitterion 2 forms very stable dimers even in DMSO, their stability is lower than of an analogous pyrrole based zwitterion 1. As revealed by the X-ray crystal structure the two binding sites in 2 cannot be planar due to steric interactions between the guanidinium group and a neighbouring aromatic CH. Hence the guanidinium moiety is twisted out of planarity from the rest of the molecule forcing the two monomers in dimer 2·2 to interact in a non-ideal orientation. Furthermore, the acidity of the NHs is lower than in 1 (as determined by UV-pH-titration also leading to less efficient binding interactions.

  4. Versatile polyion complex micelles for peptide and siRNA vectorization to engineer tolerogenic dendritic cells.

    Science.gov (United States)

    Mebarek, Naila; Vicente, Rita; Aubert-Pouëssel, Anne; Quentin, Julie; Mausset-Bonnefont, Anne-Laure; Devoisselle, Jean-Marie; Jorgensen, Christian; Bégu, Sylvie; Louis-Plence, Pascale

    2015-05-01

    Dendritic cells (DCs) are professional antigen-presenting cells that play a critical role in maintaining the balance between immunity and tolerance and, as such are a promising immunotherapy tool to induce immunity or to restore tolerance. The main challenge to harness the tolerogenic properties of DCs is to preserve their immature phenotype. We recently developed polyion complex micelles, formulated with double hydrophilic block copolymers of poly(methacrylic acid) and poly(ethylene oxide) blocks and able to entrap therapeutic molecules, which did not induce DC maturation. In the current study, the intrinsic destabilizing membrane properties of the polymers were used to optimize endosomal escape property of the micelles in order to propose various strategies to restore tolerance. On the first hand, we showed that high molecular weight (Mw) copolymer-based micelles were efficient to favor the release of the micelle-entrapped peptide into the endosomes, and thus to improve peptide presentation by immature (i) DCs. On the second hand, we put in evidence that low Mw copolymer-based micelles were able to favor the cytosolic release of micelle-entrapped small interfering RNAs, dampening the DCs immunogenicity. Therefore, we demonstrate the versatile use of polyionic complex micelles to preserve tolerogenic properties of DCs. Altogether, our results underscored the potential of such micelle-loaded iDCs as a therapeutic tool to restore tolerance in autoimmune diseases. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Self-consistent-field calculations of proteinlike incorporations in polyelectrolyte complex micelles

    NARCIS (Netherlands)

    Lindhoud, S.; Cohen Stuart, M.A.; Norde, W.; Leermakers, F.A.M.

    2009-01-01

    Self-consistent field theory is applied to model the structure and stability of polyelectrolyte complex micelles with incorporated protein (molten globule) molecules in the core. The electrostatic interactions that drive the micelle formation are mimicked by nearest-neighbor interactions using

  6. Controlled thermoreversible transfer of poly(oxazoline) micelles between an ionic liquid and water

    NARCIS (Netherlands)

    Guerrero Sanchez, C.A.; Gohy, J.M.W.; D'Haese, C.; Thijs, H.M.L.; Hoogenboom, R.; Schubert, U.S.

    2008-01-01

    Poly(2-nonyl-2-oxazoline-block-2-ethyl-2-oxazoline) block copolymer micelles were investigated as an alternative system to the approach proposed by He and Lodge (Y. He and T. P. Lodge, J. Am. Chem. Soc., 2006, 128, 12666) for the thermoreversible transfer of micelles between a hydrophobic ionic

  7. 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.

  8. Improving anticancer activity and reducing systemic toxicity of doxorubicin by self-assembled polymeric micelles

    International Nuclear Information System (INIS)

    Gou Maling; Shi Huashan; Guo Gang; Men Ke; Zhang Juan; Li Zhiyong; Luo Feng; Qian Zhiyong; Wei Yuquan; Zheng Lan; Zhao Xia

    2011-01-01

    In an attempt to improve anticancer activity and reduce systemic toxicity of doxorubicin (Dox), we encapsulated Dox in monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) micelles by a novel self-assembly procedure without using surfactants, organic solvents or vigorous stirring. These Dox encapsulated MPEG-PCL (Dox/MPEG-PCL) micelles with drug loading of 4.2% were monodisperse and ∼ 20 nm in diameter. The Dox can be released from the Dox/MPEG-PCL micelles; the Dox-release at pH 5.5 was faster than that at pH 7.0. Encapsulation of Dox in MPEG-PCL micelles enhanced the cellular uptake and cytotoxicity of Dox on the C-26 colon carcinoma cell in vitro, and slowed the extravasation of Dox in the transgenic zebrafish model. Compared to free Dox, Dox/MPEG-PCL micelles were more effective in inhibiting tumor growth in the subcutaneous C-26 colon carcinoma and Lewis lung carcinoma models, and prolonging survival of mice bearing these tumors. Dox/MPEG-PCL micelles also induced lower systemic toxicity than free Dox. In conclusion, incorporation of Dox in MPEG-PCL micelles enhanced the anticancer activity and decreased the systemic toxicity of Dox; these Dox/MPEG-PCL micelles are an interesting formulation of Dox and may have potential clinical applications in cancer therapy.

  9. 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-shellcorona...

  10. 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.

  11. Effects of gamma-irradiation on some properties of bovine casein micelles

    International Nuclear Information System (INIS)

    Saito, Zenichi

    1974-01-01

    Sedimentation studies and electron microscopic observations revealed that an association between casein micelles dispersed in water or milk serum was not induced significantly by gamma-irradiation of exposure up to 3 x 10 6 R, whereas a release of nonprotein nitrogen was observed to a certain extent. It was concluded from the results of turbidi-metry and gel filtration using 3 size groups of casein micelles, namely large, medium and small, that an irradiation-induced polymerization or association occurred within individual casein micelles, and strengthend the micelle structure. Thus the irradiated casein micelles resisted, more or less, to the solubilizing effect of NaCl, EDTA, pyrophosphate and urea. Stabilities of casein micelles for ethanol and for acidification to an isoelectric point were decreased and increased, respectively, after irradiation. Gamma irradiation also caused the decrease of glycomacropeptide released from casein micelles by the action of rennin, and this resulted in the delay of rennin-coagulation of casein. There were no essential differences among the 3 size groups of casein micelles concerning the above described tendencies. (auth.)

  12. 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.

  13. Improving anticancer activity and reducing systemic toxicity of doxorubicin by self-assembled polymeric micelles

    Energy Technology Data Exchange (ETDEWEB)

    Gou Maling; Shi Huashan; Guo Gang; Men Ke; Zhang Juan; Li Zhiyong; Luo Feng; Qian Zhiyong; Wei Yuquan [State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China); Zheng Lan; Zhao Xia, E-mail: anderson-qian@163.com [West China Second University Hospital, West China Women' s and Children' s Hospital, Sichuan University, Chengdu 610041 (China)

    2011-03-04

    In an attempt to improve anticancer activity and reduce systemic toxicity of doxorubicin (Dox), we encapsulated Dox in monomethoxy poly(ethylene glycol)-poly({epsilon}-caprolactone) (MPEG-PCL) micelles by a novel self-assembly procedure without using surfactants, organic solvents or vigorous stirring. These Dox encapsulated MPEG-PCL (Dox/MPEG-PCL) micelles with drug loading of 4.2% were monodisperse and {approx} 20 nm in diameter. The Dox can be released from the Dox/MPEG-PCL micelles; the Dox-release at pH 5.5 was faster than that at pH 7.0. Encapsulation of Dox in MPEG-PCL micelles enhanced the cellular uptake and cytotoxicity of Dox on the C-26 colon carcinoma cell in vitro, and slowed the extravasation of Dox in the transgenic zebrafish model. Compared to free Dox, Dox/MPEG-PCL micelles were more effective in inhibiting tumor growth in the subcutaneous C-26 colon carcinoma and Lewis lung carcinoma models, and prolonging survival of mice bearing these tumors. Dox/MPEG-PCL micelles also induced lower systemic toxicity than free Dox. In conclusion, incorporation of Dox in MPEG-PCL micelles enhanced the anticancer activity and decreased the systemic toxicity of Dox; these Dox/MPEG-PCL micelles are an interesting formulation of Dox and may have potential clinical applications in cancer therapy.

  14. Novel oral administrated paclitaxel micelles with enhanced bioavailability and antitumor efficacy for resistant breast cancer.

    Science.gov (United States)

    Zhang, Ting; Luo, Jingwen; Fu, Yao; Li, Hanmei; Ding, Rui; Gong, Tao; Zhang, Zhirong

    2017-02-01

    Paclitaxel (PTX) is a widely used antineoplastic drug in clinic. Due to poor aqueous solubility, it is administrated by intravenous infusion of cremophor EL containing formulation with serious adverse effects. The low oral bioavailability is a great challenge for oral formulation development. In addition, P-gp mediated multidrug resistance limit its clinical use in various resistant cancers. In this study, a novel super-antiresistant PTX micelle formulation for oral administration was developed. A P-gp inhibitor, bromotetrandrine (W198) was co-encapsulated in the micelle. The micelles were composed of Solutol HS 15 and d-a-tocopheryl polyethylene glycol succinate to avoid Cremophor EL induced toxicity. The micelles were round with a mean particle size of ∼13nm and an encapsulation efficiency of ∼90%. A series of in vitro evaluations were performed in non-resistant MCF-7 cells and resistant MCF-7/Adr cells. The super-antiresistant PTX micelles showed higher cell uptake efficiency, significantly increased cytotoxicity and antimitotic effect in drug resistant MCF-7/Adr cells when compared with Taxol and other PTX micelle formulations. Compared with Taxol, the super-antiresistant PTX micelles significantly improved bioavailability after oral administration in rats, and inhibited tumor growth in multidrug resistance xenografted MCF-7/Adr nude mice. In summary, the noval super-antiresistant PTX micelles showed a great potential for oral delivery of PTX against resistant breast cancer. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. 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

    2011-03-31

    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.

  16. Design of block-copolymer-based micelles for active and passive targeting

    NARCIS (Netherlands)

    Lebouille, Jérôme G J L; Leermakers, Frans A M; Cohen Stuart, Martien A.; Tuinier, Remco

    2016-01-01

    A self-consistent field study is presented on the design of active and passive targeting block-copolymeric micelles. These micelles form in water by self-assembly of triblock copolymers with a hydrophilic middle block and two hydrophobic outer blocks. A minority amount of diblock copolymers with the

  17. Design of block-copolymer-based micelles for active and passive targeting

    NARCIS (Netherlands)

    Lebouille, Jérôme G.J.L.; Leermakers, Frans A.M.; Cohen Stuart, Martien A.; Tuinier, Remco

    2016-01-01

    A self-consistent field study is presented on the design of active and passive targeting block-copolymeric micelles. These micelles form in water by self-assembly of triblock copolymers with a hydrophilic middle block and two hydrophobic outer blocks. A minority amount of diblock copolymers with

  18. Evaluation of iron oxide nanoparticle micelles for Magnetic Particle Imaging (MPI) of thrombosis

    NARCIS (Netherlands)

    Starmans, L.W.E.; Moonen, R.P.M.; Aussems-Custers, E.; Daemen, M.J.A.P.; Strijkers, G. J.; Nicolay, K.; Grüll, H.

    2015-01-01

    Magnetic particle imaging (MPI) is an emerging medical imaging modality that directly visualizes magnetic particles in a hot-spot like fashion. We recently developed an iron oxide nanoparticle-micelle (ION-Micelle) platform that allows highly sensitive MPI. The goal of this study was to assess the

  19. Mucoadhesive Polymer Hyaluronan as Biodegradable Cationic/Zwitterionic-Drug Delivery Vehicle

    Directory of Open Access Journals (Sweden)

    Francisco Torrens

    2015-01-01

    Full Text Available Mucoadhesive polymers in pharmaceutical formulations release drugs in mucosal areas. They interact and fix to mucus via molecular interpenetration, etc., which increase drug bioavailability. Polymers physicochemical properties affect formulation mucoadhesion, rheological behaviour and drug absorption. Hyaluronan (HA is selected as a mucoadhesive and biodegradable polymer. Geometric, topological and fractal analyses are carried out with program TOPO. Reference calculations are performed with algorithm GEPOL. Procedure TOPO underestimates molecular volume by 0.7%. Error results 5% in surface area and derived topological indices. Solvent-accessible surface is undercalculated by 3%: from hexamer HA to HA·3Ca and hydrate, the hydrophobic term rises by 42% and decays by 26%, and hydrophilic part drops by 14% and rises by 58% in agreement with the number of H-bonds. Accessibility rises by 9% and decays by 8%. Fractal dimension is underevaluated by 1% and for HA it results 1.566; on going to HA·3Ca and hydrate it rises by 2% and 1%. External-atoms dimension increases by 11%: for HA it results 1.725. When going to HA·3Ca and hydrate, it augments by 4% and 0.3%. On going from HA to HA·3Ca and hydrate, nonburied minus molecular dimension enlarges by 20% and decays by 9%. The hydrate globularity is lower than for water, Ca2+ and averages of O-atoms in HA. Ca2+ rugosity is smaller than for hydrate, averages of O-atoms in HA and water. Ca2+ and water accessibilities are greater than for hydrate. As cations exchange in HA·3Ca requires Ca2+ alteration, rises of drug zwitterionic character and acidic pH increase absorption.

  20. Anharmonic effects in IR, Raman, and Raman optical activity spectra of alanine and proline zwitterions.

    Science.gov (United States)

    Danecek, Petr; Kapitán, Josef; Baumruk, Vladimír; Bednárová, Lucie; Kopecký, Vladimír; Bour, Petr

    2007-06-14

    The difference spectroscopy of the Raman optical activity (ROA) provides extended information about molecular structure. However, interpretation of the spectra is based on complex and often inaccurate simulations. Previously, the authors attempted to make the calculations more robust by including the solvent and exploring the role of molecular flexibility for alanine and proline zwitterions. In the current study, they analyze the IR, Raman, and ROA spectra of these molecules with the emphasis on the force field modeling. Vibrational harmonic frequencies obtained with 25 ab initio methods are compared to experimental band positions. The role of anharmonic terms in the potential and intensity tensors is also systematically explored using the vibrational self-consistent field, vibrational configuration interaction (VCI), and degeneracy-corrected perturbation calculations. The harmonic approach appeared satisfactory for most of the lower-wavelength (200-1800 cm(-1)) vibrations. Modern generalized gradient approximation and hybrid density functionals, such as the common B3LYP method, provided a very good statistical agreement with the experiment. Although the inclusion of the anharmonic corrections still did not lead to complete agreement between the simulations and the experiment, occasional enhancements were achieved across the entire region of wave numbers. Not only the transitional frequencies of the C-H stretching modes were significantly improved but also Raman and ROA spectral profiles including N-H and C-H lower-frequency bending modes were more realistic after application of the VCI correction. A limited Boltzmann averaging for the lowest-frequency modes that could not be included directly in the anharmonic calculus provided a realistic inhomogeneous band broadening. The anharmonic parts of the intensity tensors (second dipole and polarizability derivatives) were found less important for the entire spectral profiles than the force field anharmonicities (third

  1. Comparison of zwitterionic N-alkylaminomethanesulfonic acids to related compounds in the Good buffer series

    Directory of Open Access Journals (Sweden)

    Robert D. Long

    2010-04-01

    Full Text Available Several N-alkyl and N,N-dialkylaminomethanesulfonic acids were synthesized (as zwitterions and/or sodium salts to be tested for utility as biological buffers at lower pH levels than existing Good buffer compounds (aminoalkanesulfonates with a minimum of two carbons between amine and sulfonic acid groups as originally described by Norman Good, and in common use as biological buffers. Our hypothesis was that a shorter carbon chain (one carbon between the amino and sulfonic acid groups should lower the ammonium ion pKa values. The alkylaminomethanesulfonate compounds were synthesized in aqueous solution by reaction of primary or secondary amines with formaldehyde/sodium hydrogensulfite addition compound. The pKa values of the ammonium ions of this series of compounds (compared to existing Good buffers was found to correlate well with the length of the carbon chain between the amino and sulfonate moeties, with a significant decrease in amine basicity in the aminomethanesulfonate compounds (pKa decrease of 2 units or more compared to existing Good buffers. An exception was found for the 2-hydroxypiperazine series which shows only a small pKa decrease, probably due to the site of protonation in this compound (as confirmed by X-ray crystal structure. X-ray crystallographic structures of two members of the series are reported. Several of these compounds have pKa values that would indicate potential utility for buffering at pH levels below the normal physiological range (pKa values in the range of 3 to 6 without aqueous solubility problems – a range that is problematic for currently available Good buffers. Unfortunately, the alkylaminomethanesulfonates were found to degrade (with loss of their buffering ability at pH levels below the pKa value and were unstable at elevated temperature (as when autoclaving – thus limiting their utility.

  2. Factors influencing casein micelle size in milk of individual cows: Genetic variants and glycosylation of k-casein

    NARCIS (Netherlands)

    Bijl, E.; Vries, de R.F.M.; Valenberg, van H.J.F.; Huppertz, T.; Hooijdonk, van A.C.M.

    2014-01-01

    The average casein micelle size varies widely between milk samples of individual cows. The factors that cause this variation in size are not known but could provide more insight into casein micelle structure and into the physiology of casein micelle formation. The objective of this research was

  3. Determination of thermodynamic potentials and the aggregation number for micelles with the mass-action model by isothermal titration calorimetry

    DEFF Research Database (Denmark)

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

    2015-01-01

    of micelles with ITC were compared to a mass-action model (MAM) of reaction type: n⋅S⇌Mn. This analysis can provide guidelines for future ITC studies of systems behaving in accordance with this model such as micelles and proteins that undergo self-association to oligomers. Micelles with small aggregation...

  4. Direct coupling of electromembrane extraction to mass spectrometry - Advancing the probe functionality toward measurements of zwitterionic drug metabolites.

    Science.gov (United States)

    Rye, Torstein Kige; Fuchs, David; Pedersen-Bjergaard, Stig; Petersen, Nickolaj Jacob

    2017-08-29

    A triple-flow electromembrane extraction (EME) probe was developed and coupled directly to electrospray-ionization mass spectrometry (ESI-MS). Metabolic reaction mixtures (pH 7.4) containing drug substances and related metabolites were continuously drawn (20 μL/min) into the EME probe in one flow channel, and mixed inside the probe with 7.5 μL min -1 of 1 M formic acid as make-up flow from a second flow channel. Following this acidification, the drug substances and their related metabolites were continuously extracted by EME at 400 V, across a supported liquid membrane (SLM) comprising 2-nitrophenyl octyl ether (and for some experiments containing 30% triphenyl phosphate (TPP)), and into 20 μL min -1 of formic acid as acceptor phase, which was introduced through a third flow channel. The acceptor phase was pumped directly to the MS system, and the ion intensity of extracted analytes was followed continuously as function of time. The triple-flow EME probe was used for co-extraction of positively charged parent drugs and their zwitterionic drug metabolites (hydroxyzine and its carboxylic acid metabolite cetirizine; and vortioxetine and its carboxylic acid metabolite Lu AA34443). While the zwitterionic metabolites could not be extracted at pH 7.4, it was shown that by acidifying the sample solution the zwitterionic metabolites could be extracted effectively. Various extraction parameters like make-up flow, extraction voltage and SLM composition were optimized for simultaneous extraction of parent drugs and metabolites. It was found that TPP added to the SLM improved extraction efficiencies of certain drug metabolites. Finally the optimized and characterized triple-flow EME probe was used for online studying the in-vitro metabolism of hydroxyzine and vortioxetine by rat liver microsomes. Due to the automated pre-extraction acidification of the rat liver microsomal solutions, it was possible to continuously monitor formation of the zwitterionic drug

  5. hERG blocking potential of acids and zwitterions characterized by three thresholds for acidity, size and reactivity

    DEFF Research Database (Denmark)

    Nikolov, Nikolai Georgiev; Dybdahl, Marianne; Jonsdottir, Svava Osk

    2014-01-01

    with a concordance of 91% by a decision tree based on the rule. Two external validations were performed with sets of 35 and 48 observations, respectively, both showing concordances of 91%. In addition, a global QSAR model of hERG blocking was constructed based on a large diverse training set of 1374 chemicals...... covering all ionization classes, externally validated showing high predictivity and compared to the decision tree. The decision tree was found to be superior for the acids and zwitterionic ampholytes classes....

  6. Complex and hierarchical micelle architectures from diblock copolymers using living, crystallization-driven polymerizations.

    Science.gov (United States)

    Gädt, Torben; Ieong, Nga Sze; Cambridge, Graeme; Winnik, Mitchell A; Manners, Ian

    2009-02-01

    Block copolymers consist of two or more chemically distinct polymer segments, or blocks, connected by a covalent link. In a selective solvent for one of the blocks, core-corona micelle structures are formed. We demonstrate that living polymerizations driven by the epitaxial crystallization of a core-forming metalloblock represent a synthetic tool that can be used to generate complex and hierarchical micelle architectures from diblock copolymers. The use of platelet micelles as initiators enables the formation of scarf-like architectures in which cylindrical micelle tassels of controlled length are grown from specific crystal faces. A similar process enables the fabrication of brushes of cylindrical micelles on a crystalline homopolymer substrate. Living polymerizations driven by heteroepitaxial growth can also be accomplished and are illustrated by the formation of tri- and pentablock and scarf architectures with cylinder-cylinder and platelet-cylinder connections, respectively, that involve different core-forming metalloblocks.

  7. Micelles from lipid derivatives of water-soluble polymers as delivery systems for poorly soluble drugs.

    Science.gov (United States)

    Lukyanov, Anatoly N; Torchilin, Vladimir P

    2004-05-07

    Polymeric micelles have a whole set of unique characteristics, which make them very promising drug carriers, in particular, for poorly soluble drugs. Our review article focuses on micelles prepared from conjugates of water-soluble polymers, such as polyethylene glycol (PEG) or polyvinyl pyrrolidone (PVP), with phospholipids or long-chain fatty acids. The preparation of micelles from certain polymer-lipid conjugates and the loading of these micelles with various poorly soluble anticancer agents are discussed. The data on the characterization of micellar preparations in terms of their morphology, stability, longevity in circulation, and ability to spontaneously accumulate in experimental tumors via the enhanced permeability and retention (EPR) effect are presented. The review also considers the preparation of targeted immunomicelles with specific antibodies attached to their surface. Available in vivo results on the efficiency of anticancer drugs incorporated into plain micelles and immunomicelles in animal models are also discussed.

  8. Synthesis of Cross-Linked Polymeric Micelle pH Nanosensors

    DEFF Research Database (Denmark)

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

    2015-01-01

    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...... 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...

  9. Factors affecting the stability of drug-loaded polymeric micelles and strategies for improvement

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Weisai; Li, Caibin; Wang, Zhiyu; Zhang, Wenli, E-mail: zwllz@163.com; Liu, Jianping, E-mail: liujianpingljp@hotmail.com [China Pharmaceutical University, Department of Pharmaceutics (China)

    2016-09-15

    Polymeric micelles (PMs) self-assembled by amphiphilic block copolymers have been used as promising nanocarriers for tumor-targeted delivery due to their favorable properties, such as excellent biocompatibility, prolonged circulation time, favorable particle sizes (10–100 nm) to utilize enhanced permeability and retention effect and the possibility for functionalization. However, PMs can be easily destroyed due to dilution of body fluid and the absorption of proteins in system circulation, which may induce drug leakage from these micelles before reaching the target sites and compromise the therapeutic effect. This paper reviewed the factors that influence stability of micelles in terms of thermodynamics and kinetics consist of the critical micelle concentration of block copolymers, glass transition temperature of hydrophobic segments and polymer–polymer and polymer–cargo interaction. In addition, some effective strategies to improve the stability of micelles were also summarized.Graphical Abstract.

  10. Polyion complex micelles prepared by self-assembly of block-graft polycation and hyperbranched polyanion

    Science.gov (United States)

    Dai, Yu; Wang, Hongquan; Zhang, Xiaojin

    2017-09-01

    Polyion complex (PIC) micelles were prepared by self-assembly of block-graft polycation monomethoxy poly(ethylene glycol)- block-(poly(ɛ-caprolactone)- graft-polyethylenimine) (PEG- b-(PCL- g-PEI)) and hyperbranched polyanion sodium carboxyl-modified hyperbranched polyesters (Hx-COONa, x = 20, 30, 40). The results from commonly used MTT assay indicated that PIC micelles had good biocompatibility. PIC micelles with N/COO- of 8/3 had appropriate size (sub-110 nm) and moderate zeta potential ( 3 mV). PIC micelles were nano-sized spheres, and the average size was about 50 nm. PIC micelles had high drug loading capacity for hydrophilic drugs such as doxorubicin (DOX) hydrochloride and released the drugs under the influence of pH and ionic strength.

  11. Folding of DsbB in mixed micelles

    DEFF Research Database (Denmark)

    Otzen, Daniel

    2003-01-01

    state and an unfolding intermediate that accumulates only under unfolding conditions at high mole fractions of SDS. The stability of DsbB is around 4.4 kcal/mol in DM, and this is halved upon reduction of the two periplasmic disulfide bonds, and is sensitive to mutagenesis. With the caveat that kinetic...... is sensitive to changes in lipid and detergent composition. As an attempt to overcome this problem, I present a kinetic analysis of the folding of a membrane protein, disulfide bond reducing protein B (DsbB), in a mixed micelle system consisting of varying molar ratios of sodium dodecyl sulfate (SDS...

  12. Radiochromic leuco dye micelle hydrogels: I. Initial investigation

    International Nuclear Information System (INIS)

    Jordan, Kevin; Avvakumov, Nikita

    2009-01-01

    This investigation reports the use of surfactants and colorless leuco triarylmethane dyes to form a new class of radiochromic micelle hydrogels for three-dimensional (3D) water-equivalent dosimetry. Gelatin gel samples with several surfactants and leuco dyes were prepared and evaluated for optical transparency, dose sensitivity and diffusion rates. The addition of Triton X-100, a non-ionic surfactant, at levels exceeding the critical micelle concentration provides a transparent hydrogel in which the water insoluble leuco Malachite Green (LMG) can dissolve. During irradiation, the LMG dye precursor converts to Malachite Green (MG + ). The most sensitive reported LMG gel formulation contains 0.3 mM LMG leuco dye, 16 mM trichloroacetic acid, 7 mM Triton X-100 and 4% w/w gelatin. A diffusion coefficient of 0.14 mm 2 h -1 was determined for MG + in this gel by fitting the time-dependent degradation of the transmission profile after irradiating half of the sample. The diffusion rate was three times lower than the standard radiochromic ferrous xylenol-orange (FX) gel. The primary feature of this 3D hydrogel is that it introduces transparent, radiochromic, micelle hydrogels. The radiochromic response to dose is instantaneous and images are stable for several hours. A dosimetric characterization revealed that the dose response is reproducible to within 10% over five separate batches and independent of both energy and dose rate. Uniform pre-irradiation of samples to 5 Gy provided a subsequent near linear response to greater than 110 Gy. LMG gels when read with a fast optical CT scanner can provide full 3D dose distributions in less than 30 min post-irradiation. LMG micelle gels scanned with a 633 nm light source are a promising system for quantitative water- or tissue-equivalent 3D dose verification in the 5-100 Gy dose range. These gels are useful for the scanning of larger volume dosimeters (i.e. >15 cm diameter) since they are easily prepared with inexpensive ingredients

  13. Block copolymer micelles as switchable templates for nanofabrication.

    Science.gov (United States)

    Krishnamoorthy, Sivashankar; Pugin, Raphaël; Brugger, Juergen; Heinzelmann, Harry; Hoogerwerf, Arno C; Hinderling, Christian

    2006-04-11

    Block copolymer inverse micelles from polystyrene-block-poly-2-vinylpyridine (PS-b-P2VP) deposited as monolayer films onto surfaces show responsive behavior and are reversibly switchable between two states of different topography and surface chemistry. The as-coated films are in the form of arrays of nanoscale bumps, which can be transformed into arrays of nanoscale holes by switching through exposure to methanol. The use of these micellar films to act as switchable etch masks for the structuring of the underlying material to form either pillars or holes depending on the switching state is demonstrated.

  14. 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

  15. Curcumin-loaded biodegradable polymeric micelles for colon cancer therapy in vitro and in vivo

    Science.gov (United States)

    Gou, Maling; Men, Ke; Shi, Huashan; Xiang, Mingli; Zhang, Juan; Song, Jia; Long, Jianlin; Wan, Yang; Luo, Feng; Zhao, Xia; Qian, Zhiyong

    2011-04-01

    Curcumin is an effective and safe anticancer agent, but its hydrophobicity inhibits its clinical application. Nanotechnology provides an effective method to improve the water solubility of hydrophobic drug. In this work, curcumin was encapsulated into monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) micelles through a single-step nano-precipitation method, creating curcumin-loaded MPEG-PCL (Cur/MPEG-PCL) micelles. These Cur/MPEG-PCL micelles were monodisperse (PDI = 0.097 +/- 0.011) with a mean particle size of 27.3 +/- 1.3 nm, good re-solubility after freeze-drying, an encapsulation efficiency of 99.16 +/- 1.02%, and drug loading of 12.95 +/- 0.15%. Moreover, these micelles were prepared by a simple and reproducible procedure, making them potentially suitable for scale-up. Curcumin was molecularly dispersed in the PCL core of MPEG-PCL micelles, and could be slow-released in vitro. Encapsulation of curcumin in MPEG-PCL micelles improved the t1/2 and AUC of curcuminin vivo. As well as free curcumin, Cur/MPEG-PCL micelles efficiently inhibited the angiogenesis on transgenic zebrafish model. In an alginate-encapsulated cancer cell assay, intravenous application of Cur/MPEG-PCL micelles more efficiently inhibited the tumor cell-induced angiogenesisin vivo than that of free curcumin. MPEG-PCL micelle-encapsulated curcumin maintained the cytotoxicity of curcumin on C-26 colon carcinoma cellsin vitro. Intravenous application of Cur/MPEG-PCL micelle (25 mg kg-1curcumin) inhibited the growth of subcutaneous C-26 colon carcinoma in vivo (p curcumin (p curcumin; this formulation can inhibit the growth of colon carcinoma through inhibiting angiogenesis and directly killing cancer cells.

  16. Soluplus/TPGS mixed micelles for dioscin delivery in cancer therapy.

    Science.gov (United States)

    Zhao, Jing; Xu, Youwei; Wang, Changyuan; Ding, Yanfang; Chen, Manyu; Wang, Yifei; Peng, Jinyong; Li, Lei; Lv, Li

    2017-07-01

    Dioscin has shown cytotoxicity against cancer cells, but its poor solubility and stability have limited its clinical application. In this study, we designed mixed micelles composed of TPGS and Soluplus ® copolymers entrapping the poorly soluble anticancer drug dioscin. In order to improve the aqueous solubility and bioactivity of dioscin, TPGS/Soluplus ® mixed micelles with an optimal ratio were prepared using a thin-film hydration method, and their physicochemical properties were characterized. Cellular cytotoxicity and uptake of the dioscin-loaded TPGS/Soluplus ® mixed micelles were studied in MCF-7 breast cancer cells and A2780s ovarian cancer cells. The pharmacokinetics of free dioscin and dioscin-loaded TPGS/Soluplus ® mixed micelles was studied in vivo in male Sprague-Dawley rats via a single intravenous injection in the tail vein. The average size of the optimized mixed micelle was 67.15 nm, with 92.59% drug encapsulation efficiency and 4.63% drug loading efficiency. The in vitro release profile showed that the mixed micelles presented sustained release behavior compared to the anhydrous ethanol solution of dioscin. In vitro cytotoxicity assays were conducted on human cancer cell lines including A2780s ovarian cancer cells and MCF-7 breast cancer cells. The mixed micelles exhibited better antitumor activity compared to free dioscin against all cell lines, which may benefit from the significant increase in the cellular uptake of dioscin from mixed micelles compared to free dioscin. The pharmacokinetic study showed that the mixed micelle formulation achieved a 1.3 times longer mean residual time (MRT) in circulation and a 2.16 times larger area under the plasma concentration-time curve (AUC) than the free dioscin solution. Our results suggest that the dioscin-loaded mixed micelles developed in this study might be a potential nano drug-delivery system for cancer chemotherapy.

  17. Fluctuations of wormlike micelle fluids in capillary flow

    Science.gov (United States)

    Salipante, Paul; Meek, Stephen; Hudson, Steven; Polymers; Complex Fluids Group Team

    2017-11-01

    We investigate the effect of entrance geometry on the flow stability of wormlike micelles solutions in capillary flow. These solutions exhibit strong shear thinning behavior resulting from micelle breakage and have been observed to undergo large flow rate fluctuations. We investigate these fluctuations using simultaneous measurements of flow rate and pressure drop across a capillary, and we adjust entrance geometry. With a tapered constriction, we observe large persistent fluctuations above a critical flow rate, characterized by rapid decreases in the pressure drop with corresponding increase in flow rate followed by a period of recovery where pressure increases and flow rate decreases. Flow field observations in the tapered entrance show large flow circulations. An abrupt contraction produces smaller transient fluidized jets forming upstream of the constriction and the magnitude of the fluctuations are significantly diminished. The effect of fluid properties is studied by comparing the magnitude and timescales of the fluctuations for surfactant systems with different relaxation times. The onset of fluctuations is compared to a criterion for the onset of elastic instabilities and the magnitude is compared to estimates for changes in channel resistance. NIST on a Chip.

  18. Versatile antifouling polyethersulfone filtration membranes modified via surface grafting of zwitterionic polymers from a reactive amphiphilic copolymer additive.

    Science.gov (United States)

    Zhao, Yi-Fan; Zhang, Pei-Bin; Sun, Jian; Liu, Cui-Jing; Yi, Zhuan; Zhu, Li-Ping; Xu, You-Yi

    2015-06-15

    Here we describe the development of versatile antifouling polyethersulfone (PES) filtration membranes modified via surface grafting of zwitterionic polymers from a reactive amphiphilic copolymer additive. Amphiphilic polyethersulfone-block-poly(2-hydroxyethyl methacrylate) (PES-b-PHEMA) was beforehand designed and used as the blending additive of PES membranes prepared by phase inversion technique. The surface enriched PHEMA blocks on membrane surface acted as an anchor to immobilize the initiating site. Poly(sulfobetaine methacrylate) (PSBMA) were subsequently grafted onto the PES blend membranes by surface-initiated atom transfer radical polymerization (SI-ATRP). The analysis of surface chemistry confirmed the successful grafting of zwitterionic PSBMA brushes on PES membrane surface. The resulted PES-g-PSBMA membranes were capable of separating proteins from protein solution and oil from oil/water emulsion efficiently. Furthermore, the modified membranes showed high hydrophilicity and strongly antifouling properties due to the incorporation of well-defined PSBMA layer. In addition, the PES-g-PSBMA membranes exhibited excellent blood compatibility and durability during the washing process. The developed antifouling PES membranes are versatile and can find their applications in protein filtration, blood purification and oil/water separation, etc. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Preparation and characterization of novel zwitterionic poly(arylene ether sulfone) ultrafiltration membrane with good thermostability and excellent antifouling properties

    Science.gov (United States)

    Rong, Guolong; Zhou, Di; Han, Xiaocui; Pang, Jinhui

    2018-01-01

    Zwitterionic poly(arylene ether sulfone) (PAES-NS) was synthesized via copolymerization by using a bisphenol monomer with a pyridine group. The chemical structures of the copolymers were confirmed by using Fourier transform infrared (FTIR) and 1H nuclear magnetic resonance (NMR) spectroscopy; the copolymers showed good thermal stability. A series of polyphenysulfone (PPSU)/PAES-NS blend ultrafiltration (UF) membranes was prepared via conventional immersion precipitation phase inversion methods The morphologies of the modified membranes were investigated by scanning electron microscopy (SEM). The surface hydrophilicity of the UF membranes was studied by water contact angle measurement, indicating that the zwitterionic group increased the membrane hydrophilicity. UF of solvated model pollutants using the membranes showed a significant reduction of the irreversible adsorption of the foulants, illustrating the excellent anti-fouling properties of the membrane. The water flux of the PAES-NS membrane was significantly enhanced, being almost three times higher than that of the pristine PPSU membrane, with retention of a high rejection level. After three UF cycles, the water flux recovery of the PAES-NS membrane was as high as 96%.

  20. Synthesis and solution aggregation studies of a suite of mixed neutral and zwitterionic chromophores for second-order nonlinear optics.

    Science.gov (United States)

    Peddie, Victoria; Anderson, Jack; Harvey, Joanne E; Smith, Gerald J; Kay, Andrew

    2014-11-07

    We report details of the synthesis of a series of bi- and trichromophores. These compounds contain mixtures of chromophores that have zwitterionic (ZWI) and neutral ground state (NGS) components covalently attached to each other. The neutral ground state moieties are based on dyes with aniline donors--such as Disperse Red 1--whereas the zwitterionic components are derived from chromophores with pro-aromatic donors such as 1,4-dihydropyridinylidene. By combining both ZWI and NGS components, we aim to develop novel compounds for nonlinear optics in which there is an enhancement of the overall hyperpolarizability coupled with a decrease in the net dipole moment. Thus, this approach should eliminate the electrostatic effects that result when only one type of chromophore is used, and so reduce the likelihood of undesirable aggregation occurring. This, in turn, should enable us to realize organic materials with large macroscopic optical nonlinearities. An analysis of the UV-vis results suggests that there is a strong dependence on solvent polarity that determines whether the embedded constituents should be treated as discrete elements; in low polarity solvents, there appear to be strong intramolecular interactions occurring, particularly when a 1,4-quinolinylidene-based donor is used in the ZWI component.

  1. Hydrophobic radical influence on structure and vibration spectra of zwitter-ionic forms of glycine and alanine in condensed state

    International Nuclear Information System (INIS)

    Ten, G.N.; Kadrov, D.M.; Baranov, V.I.

    2014-01-01

    Structure and vibrational spectra of the zwitter-ionic forms of glycine and alanine in water solution and solid state have been calculated in the B3LYP/6-311++G(d,p) approximation. The environment influence has been taken into account by two methods: the self-consistent reaction field (SCRF) method and one of modeling the glycine and alanine complexes with molecules of water. The structure, energy and spectral properties have been determined which allow establishing an influence of the hydrophobic radical on the glycine and alanine ability to form the hydrogen bonds. It is shown by comparison with experiment that for the calculation of vibrational (IR and Raman) spectra of the zwitter-ionic forms of glycine and alanine in the condensed states they must be surrounded with three molecules of water, one of which is located between the N + H 3 and COO - ionic groups. The value of energy necessary to form the Ala complexes with water compared to Gly ones is 56.47 and 12.55 kcal/mol higher in the case of the complex formation with 1and 3 molecules of water, respectively, located between bipolar groups. (authors)

  2. Switching wormlike micelles of selenium-containing surfactant using redox reaction.

    Science.gov (United States)

    Zhang, Yongmin; Kong, Weiwei; Wang, Cheng; An, Pengyun; Fang, Yun; Feng, Yujun; Qin, Zhirong; Liu, Xuefeng

    2015-10-14

    A novel redox-switchable wormlike micellar system was developed based on a mixture of selenium-containing zwitterionic surfactant and commercially available anionic surfactant sodium dodecyl sulfate, which reversibly and quickly responds to H2O2 and vitamin C, and shows circulatory gel/sol transition, reflecting changes in aggregate morphology from entangled worms to vesicles.

  3. Self-Assembly of Calix[4]arene-Based Amphiphiles Bearing Polyethylene Glycols: Another Example of "Platonic Micelles".

    Science.gov (United States)

    Yoshida, Kenta; Fujii, Shota; Takahashi, Rintaro; Matsumoto, Sakiko; Sakurai, Kazuo

    2017-09-12

    The aggregation number of classical micelles exhibits a certain distribution, which is a recognizable feature of conventional micelles. However, we recently identified perfectly monodisperse calix[4]arene-based micelles whose aggregation numbers agree with the vertex numbers of regular polyhedra, that is, Platonic solids, and thus they are named "Platonic micelles". Regarding our hypothesis of the formation mechanism of Platonic micelles, both repulsive interactions including steric hindrance and electrostatic repulsions among the headgroups are important for determining their aggregation number; however, neither of these is necessarily needed to consider. In this study, we employed polyethylene glycols (PEGs) as the nonionic headgroup of calix[4]arene-based amphiphiles to study the effects of only repulsive interactions caused by steric hindrance on the formation of Platonic micelles. The amphiphiles containing relatively low-molecular-weight PEGs (550 or 1000 g mol -1 ) form dodecamer or octamer micelles, respectively, with no variation in the aggregation number. However, relatively high-molecular-weight PEGs (2000 g mol -1 ) produce polydispersed micelles with a range of aggregation number. PEG 2000 exhibits a greater affinity for water than PEG 550 and 1000, resulting in fewer hydrophobic interactions in micelle formation, as indicated by the drastic increase of the critical micelle concentration (CMC) value in the PEG 2000 system. The instability of the structure of PEG 2k CaL5 micelles might contribute to the higher mobility of PEG in the micellar shell, resulting in a non-Platonic aggregation number with polydispersity.

  4. Chemical exchange in novel spirobicyclic zwitterionic Janovsky complexes using dynamic 1H NMR spectroscopy.

    Science.gov (United States)

    Culf, A S; Cuperlović-Culf, M; Ouellette, R J

    2009-02-01

    Highly coloured Janovsky complexes have been known for over 120 years, being used in many colourimetric analytical procedures. In this present study, two novel and stable nitrocyclohexadienyl spirobicyclic, zwitterionic Janovsky anionic hydantoin sigma-complexes, rac-1,3-diisopropyl-6-nitro-2,4-dioxo-1,3-diazaspiro[4.5]deca-6,9-dien-8-ylideneazinate, ammonium internal salt (1) and 1,3-diisopropyl-2,4-dioxo-1,3-diazaspiro[4.5]deca-6,9-dien-8-ylideneazinate, ammonium internal salt (2) have been prepared and characterised by NMR, electrospray ionization mass spectrometry (ESI-MS) and UV/visible methods. For the p-mononitro-substituted complex (2), we discovered chemical exchange behaviour using 1D saturation transfer and 2D exchange spectroscopy (EXSY) (1)H NMR techniques. The coalescence temperature was determined to be 62 degrees C in d(3)-acetonitrile. Analysis of these data provided a Gibbs free energy of activation, DeltaG double dagger, of + 67 kJ mole(-1), a rate constant, k, coalescence of 220 Hz and an equilibrium constant, K(eqm), of 0.98 as estimates of the exchange process in this solvent. Of the two mechanisms proposed for this fluxional behaviour, ring opening to a substituted benzene or proton exchange, a further theoretical modelling study of 1D (1)H NMR spectra was able to confirm that simple proton exchange between the two nitrogen sites of the hydantoin ring provided an accurate simulation of the observed experimental evidence. Interestingly, the o,p-dinitro-substituted complex (1) did not show any chemical exchange behaviour up to 150 degrees C in d(3)-acetonitrile (to 75 degrees C) and d(6)-dimethyl sulfoxide (DMSO). Molecular modelling at the MM2 level suggests that steric collisions of an N-acyl isopropyl substituent of the hydantoin ring with the ortho-nitro group of the spirofused cyclohexadienyl ring prevents the proposed proton exchange mechanism occurring in this case. 2008 Crown in the right of Canada. Published by John Wiley & Sons, Ltd.

  5. Indium tin oxide with zwitterionic interfacial design for biosensing applications in complex matrices

    Energy Technology Data Exchange (ETDEWEB)

    Darwish, Nadia T.; Alias, Yatimah; Khor, Sook Mei, E-mail: naomikhor@um.edu.my

    2015-01-15

    Graphical abstract: - Highlights: • The incorporation of a linker and antifouling molecules is an important interfacial design for both affinity and enzymatic biosensors. • The resistance to non-specific protein adsorptions of BSA–FITC and RBITC–Cyt c were determined by confocal laser scanning microscopy. • The antifouling interface allows detection of target analytes in highly complicated biological matrices. - Abstract: Biosensing interfaces consisting of linker molecules (COOH or NH{sub 2}) and charged, antifouling moieties ((-SO{sup 3−} and N{sup +}(Me){sub 3}) for biosensing applications were prepared for the first time by the in situ deposition of mixtures of aryl diazonium cations on indium tin oxide (ITO) electrodes. A linker molecule is required for the attachment of biorecognition molecules (e.g., antibodies, enzymes, DNA chains, and aptamers) close to the transducer surface. The attached molecules improve the biosensing sensitivity and also provide a short response time for analyte detection. Thus, the incorporation of a linker and antifouling molecules is an important interfacial design for both affinity and enzymatic biosensors. The reductive adsorption behavior and electrochemical measurement were studied for (1) an individual compound and (2) a mixture of antifouling zwitterionic molecules together with linker molecules [combination 1: 4-sulfophenyl (SP), 4-trimethylammoniophenyl (TMAP), and 1,4-phenylenediamine (PPD); combination 2: 4-sulfophenyl (SP), 4-trimethylammoniophenyl (TMAP), and 4-aminobenzoic acid (PABA)] of aryl diazonium cations grafted onto an ITO electrode. The mixture ratios of SP:TMAP:PPD and SP:TMAP:PABA that provided the greatest resistance to non-specific protein adsorptions of bovine serum albumin labeled with fluorescein isothiocyanate (BSA–FITC) and cytochrome c labeled with rhodamine B isothiocyanate (RBITC–Cyt c) were determined by confocal laser scanning microscopy (CLSM). For the surface antifouling study

  6. Indium tin oxide with zwitterionic interfacial design for biosensing applications in complex matrices

    International Nuclear Information System (INIS)

    Darwish, Nadia T.; Alias, Yatimah; Khor, Sook Mei

    2015-01-01

    Graphical abstract: - Highlights: • The incorporation of a linker and antifouling molecules is an important interfacial design for both affinity and enzymatic biosensors. • The resistance to non-specific protein adsorptions of BSA–FITC and RBITC–Cyt c were determined by confocal laser scanning microscopy. • The antifouling interface allows detection of target analytes in highly complicated biological matrices. - Abstract: Biosensing interfaces consisting of linker molecules (COOH or NH 2 ) and charged, antifouling moieties ((-SO 3− and N + (Me) 3 ) for biosensing applications were prepared for the first time by the in situ deposition of mixtures of aryl diazonium cations on indium tin oxide (ITO) electrodes. A linker molecule is required for the attachment of biorecognition molecules (e.g., antibodies, enzymes, DNA chains, and aptamers) close to the transducer surface. The attached molecules improve the biosensing sensitivity and also provide a short response time for analyte detection. Thus, the incorporation of a linker and antifouling molecules is an important interfacial design for both affinity and enzymatic biosensors. The reductive adsorption behavior and electrochemical measurement were studied for (1) an individual compound and (2) a mixture of antifouling zwitterionic molecules together with linker molecules [combination 1: 4-sulfophenyl (SP), 4-trimethylammoniophenyl (TMAP), and 1,4-phenylenediamine (PPD); combination 2: 4-sulfophenyl (SP), 4-trimethylammoniophenyl (TMAP), and 4-aminobenzoic acid (PABA)] of aryl diazonium cations grafted onto an ITO electrode. The mixture ratios of SP:TMAP:PPD and SP:TMAP:PABA that provided the greatest resistance to non-specific protein adsorptions of bovine serum albumin labeled with fluorescein isothiocyanate (BSA–FITC) and cytochrome c labeled with rhodamine B isothiocyanate (RBITC–Cyt c) were determined by confocal laser scanning microscopy (CLSM). For the surface antifouling study, we used 2

  7. Indium tin oxide with zwitterionic interfacial design for biosensing applications in complex matrices

    Science.gov (United States)

    Darwish, Nadia T.; Alias, Yatimah; Khor, Sook Mei

    2015-01-01

    Biosensing interfaces consisting of linker molecules (COOH or NH2) and charged, antifouling moieties ((sbnd SO3- and N+(Me)3) for biosensing applications were prepared for the first time by the in situ deposition of mixtures of aryl diazonium cations on indium tin oxide (ITO) electrodes. A linker molecule is required for the attachment of biorecognition molecules (e.g., antibodies, enzymes, DNA chains, and aptamers) close to the transducer surface. The attached molecules improve the biosensing sensitivity and also provide a short response time for analyte detection. Thus, the incorporation of a linker and antifouling molecules is an important interfacial design for both affinity and enzymatic biosensors. The reductive adsorption behavior and electrochemical measurement were studied for (1) an individual compound and (2) a mixture of antifouling zwitterionic molecules together with linker molecules [combination 1: 4-sulfophenyl (SP), 4-trimethylammoniophenyl (TMAP), and 1,4-phenylenediamine (PPD); combination 2: 4-sulfophenyl (SP), 4-trimethylammoniophenyl (TMAP), and 4-aminobenzoic acid (PABA)] of aryl diazonium cations grafted onto an ITO electrode. The mixture ratios of SP:TMAP:PPD and SP:TMAP:PABA that provided the greatest resistance to non-specific protein adsorptions of bovine serum albumin labeled with fluorescein isothiocyanate (BSA-FITC) and cytochrome c labeled with rhodamine B isothiocyanate (RBITC-Cyt c) were determined by confocal laser scanning microscopy (CLSM). For the surface antifouling study, we used 2-[2-(2-methoxyethoxy) ethoxy]acetic acid (OEG) as a standard control because of its prominent antifouling properties. Surface compositions of combinations 1 and 2 were characterized using X-ray photoelectron spectroscopy (XPS). Field-emission scanning electron microscopy (FE-SEM) was used to characterize the morphology of the grafted films to confirm the even distribution between linker and antifouling molecules grafted onto the ITO surfaces

  8. Effects of surfactant micelles on viscosity and conductivity of poly(ethylene glycol) solutions

    Science.gov (United States)

    Wang, Shun-Cheng; Wei, Tzu-Chien; Chen, Wun-Bin; Tsao, Heng-Kwong

    2004-03-01

    The neutral polymer-micelle interaction is investigated for various surfactants by viscometry and electrical conductometry. In order to exclude the well-known necklace scenario, we consider aqueous solutions of low molecular weight poly(ethylene glycol) (2-20)×103, whose radial size is comparable to or smaller than micelles. The single-tail surfactants consist of anionic, cationic, and nonionic head groups. It is found that the viscosity of the polymer solution may be increased several times by micelles if weak attraction between a polymer segment and a surfactant exists, ɛmicelles. Even though ɛ is small, the interaction energy between a macromolecule and a micelle can be a few kBT due to many contacts, and thus leads to polymer adsorption on micelles' surfaces. The rapid growth of the viscosity with surfactant concentration is therefore attributed to the considerable cross links among micelles and polymers (transient network). In addition to substantial alteration of the transport properties, this weak interaction also influences the onset point of thermodynamic instability associated with polymer-surfactant solutions. The examples include the decrease of critical aggregation concentration for ionic surfactant and clouding point for nonionic surfactant due to PEG addition.

  9. A Novel Solubility-Enhanced Rubusoside-Based Micelles for Increased Cancer Therapy

    Science.gov (United States)

    Zhang, Meiying; Dai, Tongcheng; Feng, Nianping

    2017-04-01

    Many anti-cancer drugs have a common problem of poor solubility. Increasing the solubility of the drugs is very important for its clinical applications. In the present study, we revealed that the solubility of insoluble drugs was significantly enhanced by adding rubusoside (RUB). Further, it was demonstrated that RUB could form micelles, which was well characterized by Langmuir monolayer investigation, transmission electron microscopy, atomic-force microscopy, and cryogenic transmission electron microscopy. The RUB micelles were ellipsoid with the horizontal distance of 25 nm and vertical distance of 1.2 nm. Insoluble synergistic anti-cancer drugs including curcumin and resveratrol were loaded in RUB to form anti-cancer micelles RUB/CUR + RES. MTT assay showed that RUB/CUR + RES micelles had more significant toxicity on MCF-7 cells compared to RUB/CUR micelles + RUB/RES micelles. More importantly, it was confirmed that RUB could load other two insoluble drugs together for remarkably enhanced anti-cancer effect compared to that of RUB/one drug + RUB/another drug. Overall, we concluded that RUB-based micelles could efficiently load insoluble drugs for enhanced anti-cancer effect.

  10. HPMA-based polymeric micelles for curcumin solubilization and inhibition of cancer cell growth.

    Science.gov (United States)

    Naksuriya, Ornchuma; Shi, Yang; van Nostrum, Cornelus F; Anuchapreeda, Songyot; Hennink, Wim E; Okonogi, Siriporn

    2015-08-01

    Curcumin (CM) has been reported as a potential anticancer agent. However, its pharmaceutical applications as therapeutic agent are hampered because of its poor aqueous solubility. The present study explores the advantages of polymeric micelles composed of block copolymers of methoxypoly(ethylene glycol) (mPEG) and N-(2-hydroxypropyl) methacrylamide (HPMA) modified with monolactate, dilactate and benzoyl side groups to enhance CM solubility and inhibitory activity against cancer cells. Amphiphilic block copolymers, ω-methoxypoly(ethylene glycol)-b-(N-(2-benzoyloxypropyl) methacrylamide) (PEG-HPMA-Bz) were synthesized and characterized by (1)H NMR and GPC. One polymer with a molecular weight of 28,000Da was used to formulate CM and compared with other aromatic substituted polymers. CM was loaded by a fast heating method (PEG-HPMA-DL and PEG-HPMA-Bz-L) and a nanoprecipitation method (PEG-HPMA-Bz). Physicochemical characteristics and cytotoxicity/cytocompatibility of the CM loaded polymeric micelles were evaluated. It was found that HPMA-based polymeric micelles significantly enhanced the solubility of CM. The PEG-HPMA-Bz micelles showed the best solubilization properties. CM loaded polymeric micelles showed sustained release of the loading CM for more than 20days. All of CM loaded polymeric micelles formulations showed a significantly potent cytotoxic effect against three cancer cell lines. HPMA-based polymeric micelles are therefore promising nanodelivery systems of CM for cancer therapy. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. 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.

  12. Green Tea Catechin-Based Complex Micelles Combined with Doxorubicin to Overcome Cardiotoxicity and Multidrug Resistance

    Science.gov (United States)

    Cheng, Tangjian; Liu, Jinjian; Ren, Jie; Huang, Fan; Ou, Hanlin; Ding, Yuxun; Zhang, Yumin; Ma, Rujiang; An, Yingli; Liu, Jianfeng; Shi, Linqi

    2016-01-01

    Chemotherapy for cancer treatment has been demonstrated to cause some side effects on healthy tissues and multidrug resistance of the tumor cells, which greatly limits therapeutic efficacy. To address these limitations and achieve better therapeutic efficacy, combination therapy based on nanoparticle platforms provides a promising approach through delivering different agents simultaneously to the same destination with synergistic effect. In this study, a novel green tea catechin-based polyion complex (PIC) micelle loaded with doxorubicin (DOX) and (-)-Epigallocatechin-3-O-gallate (EGCG) was constructed through electrostatic interaction and phenylboronic acid-catechol interaction between poly(ethylene glycol)-block-poly(lysine-co-lysine-phenylboronic acid) (PEG-PLys/PBA) and EGCG. DOX was co-loaded in the PIC micelles through π-π stacking interaction with EGCG. The phenylboronic acid-catechol interaction endowed the PIC micelles with high stability under physiological condition. Moreover, acid cleavability of phenylboronic acid-catechol interaction in the micelle core has significant benefits for delivering EGCG and DOX to same destination with synergistic effects. In addition, benefiting from the oxygen free radicals scavenging activity of EGCG, combination therapy with EGCG and DOX in the micelle core could protect the cardiomyocytes from DOX-mediated cardiotoxicity according to the histopathologic analysis of hearts. Attributed to modulation of EGCG on P-glycoprotein (P-gp) activity, this kind of PIC micelles could effectively reverse multidrug resistance of cancer cells. These results suggested that EGCG based PIC micelles could effectively overcome DOX induced cardiotoxicity and multidrug resistance. PMID:27375779

  13. In vitro evaluation of antioxidant and neuroprotective effects of curcumin loaded in Pluronic micelles

    Directory of Open Access Journals (Sweden)

    Cvetelina Gorinova

    2016-09-01

    Full Text Available Curcumin is a polyphenolic substance with attractive pharmacological activities (e.g. antioxidant, anti-inflammatory, anticancer. Incorporation of curcumin in polymeric micelles could overcome the problems associated with its instability and low aqueous solubility. The aim of this study was to load curcumin in polymeric micelles based on Pluronic® P 123 or Pluronic® F 127 triblock copolymers and evaluate the antioxidant and neuroprotective effects after micellization. The micelles were prepared and loaded with curcumin by applying the dissolution method. Higher encapsulation efficiency was observed in the micelles formulated with Pluronic® P 123. These micelles were characterized with small size and narrow size distribution. The effects of micellar curcumin were investigated in two in vitro models. First, the capacity of micellar curcumin to inhibit iron/ascorbic acid-induced lipid peroxidation in rat liver microsomes was evaluated. Micellar curcumin and free drug showed similar inhibition of lipid peroxidation. Second, micellar curcumin and free curcumin showed protective potential in a model of 6-hydroxydopamine induced neurotoxicity in rat brain synaptosomes. The results from both methods indicated preservation of antioxidant and neuroprotective activity of curcumin in micelles. The small micellar size, high loading capacity and preservation of antioxidant activity of curcumin into Pluronic micelles, suggested their further evaluation as a curcumin delivery system.

  14. pH-Responsive Micelle-Based Cytoplasmic Delivery System for Induction of Cellular Immunity

    Directory of Open Access Journals (Sweden)

    Eiji Yuba

    2017-11-01

    Full Text Available (1 Background: Cytoplasmic delivery of antigens is crucial for the induction of cellular immunity, which is an important immune response for the treatment of cancer and infectious diseases. To date, fusogenic protein-incorporated liposomes and pH-responsive polymer-modified liposomes have been used to achieve cytoplasmic delivery of antigen via membrane rupture or fusion with endosomes. However, a more versatile cytoplasmic delivery system is desired for practical use. For this study, we developed pH-responsive micelles composed of dilauroyl phosphatidylcholine (DLPC and deoxycholic acid and investigated their cytoplasmic delivery performance and immunity-inducing capability. (2 Methods: Interaction of micelles with fluorescence dye-loaded liposomes, intracellular distribution of micelles, and antigenic proteins were observed. Finally, antigen-specific cellular immune response was evaluated in vivo using ELIspot assay. (3 Results: Micelles induced leakage of contents from liposomes via lipid mixing at low pH. Micelles were taken up by dendritic cells mainly via macropinocytosis and delivered ovalbumin (OVA into the cytosol. After intradermal injection of micelles and OVA, OVA-specific cellular immunity was induced in the spleen. (4 Conclusions: pH-responsive micelles composed of DLPC and deoxycholic acid are promising as enhancers of cytosol delivery of antigens and the induction capability of cellular immunity for the treatment of cancer immunotherapy and infectious diseases.

  15. EPR spin probe and spin label studies of some low molecular and polymer micelles

    Science.gov (United States)

    Wasserman, A. M.; Kasaikin, V. A.; Timofeev, V. P.

    1998-12-01

    The rotational mobility of spin probes of different shape and size in low molecular and polymer micelles has been studied. Several probes having nitroxide fragment localized either in the vicinity of micelle interface or in the hydrocarbon core have been used. Upon increasing the number of carbon atoms in hydrocarbon chain of detergent from 7 to 13 (sodium alkyl sulfate micelles) or from 12 to 16 (alkyltrimethylammonium bromide micelles) the rotational mobility of spin probes is decreased by the factor 1.5-2.0. The spin probe rotational mobility in polymer micelles (the complexes of alkyltrimethylammonium bromides and polymethacrylic or polyacrylic acids) is less than mobility in free micelles of the same surfactants. The study of EPR-spectra of spin labeled polymethacrylic acid (PMA) indicated that formation of water soluble complexes of polymer and alkyltrimethylammonium bromides in alkaline solutions (pH 9) does not affect the polymer segmental mobility. On the other hand, the polymer complexes formation in slightly acidic water solution (pH 6) breaks down the compact PMA conformation, thus increasing the polymer segmental mobility. Possible structures of polymer micelles are discussed.

  16. Detergent extraction of herpes simplex virus type 1 glycoprotein D by zwitterionic and non-ionic detergents and purification by ion-exchange high-performance liquid chromatography

    NARCIS (Netherlands)

    Welling-Wester, S; Feijlbrief, M; Koedijk, DGAM; Welling, GW

    1998-01-01

    Detergents (surfactants) are the key reagents in the extraction and purification of integral membrane proteins. Zwitterionic and non-ionic detergents were used for the extraction of recombinant glycoprotein D (gD-1) of herpes simplex virus type 1 (HSV-1) from insect cells infected with recombinant

  17. Fabrication of an Anti-Biofouling Plasma-Filtration Membrane by an Electrospinning Process Using Photo-Cross-linkable Zwitterionic Phospholipid Polymers.

    Science.gov (United States)

    Seo, Jiae; Seo, Ji-Hun

    2017-06-14

    The goal of this study is to fabricate a stable plasma filtration membrane with antibiofouling properties via an electrospinning process. To this end, a random-type copolymer consisting of zwitterionic phosphorylcholine (PC) groups and ultraviolet (UV)-cross-linkable phenyl azide groups was synthesized. The zwitterionic PC group provides antibiofouling properties, and the phenyl azide group enables the stable maintenance of the fibrous nanostructure of hydrophilic zwitterion polymers in aqueous medium via a simple UV curing process. To demonstrate the antibiofouling nature of the PC group, a polymer without antibiofouling PC groups was also prepared for comparison. The successful synthesis of the random-type copolymers containing phenyl azide groups was proven by 1 H nuclear magnetic resonance and Fourier transform infrared spectroscopy, and the fibrous structure of the prepared membranes was observed by field emission scanning electron microscopy. The antibiofouling properties were analyzed by fluorescein isothiocyanate-labeled bovine serum albumin adsorption and platelet adhesion tests. The experimental results show that membranes containing zwitterionic PC groups exhibited obvious decreases in platelet adhesion and protein adsorption. Platelet-rich plasma solution was filtered using the prepared membranes to test their filtration properties. The sequential filtration process removed 80% and almost 98% of the platelets. This finding confirmed that the membrane retained its blood-inert biomaterial surface in a complex medium that included blood plasma and platelets.

  18. Water swelling, brine soluble imidazole based zwitterionic polymers-synthesis and study of reversible UCST behaviour and gel-sol transitions

    NARCIS (Netherlands)

    Vasantha, Vivek Arjunan; Jana, Satyasankar; Parthiban, Anbanandam; Vancso, Julius G.

    2014-01-01

    New vinylbenzene substituted imidazole based zwitterionic polymers with unique characteristics like swelling in water and solubility in concentrated brine solution in which they exhibited a reversible upper critical solution temperature (UCST) and gel-sol transitions are reported herein. © 2014 The

  19. Dicationic and zwitterionic catalysts for the amine-initiated, immortal ring-opening polymerisation of rac-lactide: facile synthesis of amine-terminated, highly heterotactic PLA

    NARCIS (Netherlands)

    Clark, L.; Cushion, M.G.; Dyer, H.E.; Schwarz, A.D.; Duchateau, R.; Mountford, P.

    2010-01-01

    Dicationic, zwitterionic and conventional yttrium compounds act as catalysts for the primary or secondary amine-initiated immortal ROP of rac-lactide; amine-terminated, highly heterotactic poly(rac-lactides) with narrow polydispersities and well-controlled molecular weights are prepared in this

  20. Nanotoxicity comparison of four amphiphilic polymeric micelles with similar hydrophilic or hydrophobic structure.

    Science.gov (United States)

    Zhao, Bo; Wang, Xue-Qing; Wang, Xiao-You; Zhang, Hua; Dai, Wen-Bing; Wang, Jun; Zhong, Zhen-Lin; Wu, Hou-Nan; Zhang, Qiang

    2013-10-03

    Nanocarriers represent an attractive means of drug delivery, but their biosafety must be established before their use in clinical research. Four kinds of amphiphilic polymeric (PEG-PG-PCL, PEEP-PCL, PEG-PCL and PEG-DSPE) micelles with similar hydrophilic or hydrophobic structure were prepared and their in vitro and in vivo safety were evaluated and compared. In vitro nanotoxicity evaluations included assessments of cell morphology, cell volume, inflammatory effects, cytotoxicity, apoptosis and membrane fluidity. An umbilical vein cell line (Eahy.926) and a kind of macrophages (J774.A1) were used as cell models considering that intravenous route is dominant for micelle delivery systems. In vivo analyses included complete blood count, lymphocyte subset analysis, detection of plasma inflammatory factors and histological observations of major organs after intravenous administration to KM mice. All the micelles enhanced inflammatory molecules in J774.A1 cells, likely resulting from the increased ROS levels. PEG-PG-PCL and PEEP-PCL micelles were found to increase the J774.A1 cell volume. This likely correlated with the size of PEG-PG-PCL micelles and the polyphosphoester structure in PEEP-PCL. PEG-DSPE micelles inhibited the growth of Eahy.926 cells via inducing apoptosis. This might relate to the structure of DSPE, which is a type of phospholipid and has good affinity with cell membrane. No evidence was found for cell membrane changes after treatment with these micelles for 24 h. In the in vivo study, during 8 days of 4 time injection, each of the four nanocarriers altered the hematic phase differently without changes in inflammatory factors or pathological changes in target organs. These results demonstrate that the micelles investigated exhibit diverse nanotoxicity correlated with their structures, their biosafety is different in different cell model, and there is no in vitro and in vivo correlation found. We believe that this study will certainly provide more

  1. Backbone-hydrazone-containing biodegradable copolymeric micelles for anticancer drug delivery

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Jing; Luan, Shujuan; Qin, Benkai; Wang, Yingying; Wang, Kai; Qi, Peilan; Song, Shiyong, E-mail: pharmsong@henu.edu.cn [Henan University, Institute of Pharmacy (China)

    2016-11-15

    Well-defined biodegradable, pH-sensitive amphiphilic block polymers, poly(ethylene glycol)-Hyd-poly(lactic acid) (mPEG-Hyd-PLA) which have acid-cleavable linkages in their backbones, were synthesized via ring-opening polymerization initiated from hydrazone-containing macroinitiators. Introducing a hydrazone bond onto the backbone of an amphiphilic copolymer will find a broad-spectrum encapsulation of hydrophobic drugs. Dynamic light scattering (DLS) and transmission electron microscopy showed that the diblock copolymers self-assembled into stable micelles with average diameters of 100 nm. The mean diameters and size distribution of the hydrazone-containing micelles changed obviously in mildly acidic pH (multiple peaks from 1 to 202 nm appeared under a pH 4.0 condition) than in neutral, while there were no changes in the case of non-sensitive ones. Doxorubicin (DOX) and paclitaxel (PTX) were loaded with drug loading content ranging from 2.4 to 3.5 %, respectively. Interestingly, the anticancer drugs released from mPEG-Hyd-PLA micelles could also be promoted by the increased acidity. An in vitro cytotoxicity study showed that the DOX-loaded mPEG-Hyd-PLA micelles have significantly enhanced cytotoxicity against HepG2 cells compared with the non-sensitive poly(ethylene glycol)-block-poly(lactic acid) (mPEG-PLA) micelles. Confocal microscopy observation indicated that more DOX were delivered into the nuclei of cells following 6 or 12 h incubation with DOX-loaded mPEG-Hyd-PLA micelles. In vivo studies on H22-bearing Swiss mice demonstrated the superior anticancer activity of DOX-loaded mPEG-Hyd-PLA micelles over free DOX and DOX-loaded mPEG-PLA micelles. These hydrazone-containing pH-responsive degradable micelles provide a useful strategy for antitumor drug delivery.

  2. Backbone-hydrazone-containing biodegradable copolymeric micelles for anticancer drug delivery

    International Nuclear Information System (INIS)

    Xu, Jing; Luan, Shujuan; Qin, Benkai; Wang, Yingying; Wang, Kai; Qi, Peilan; Song, Shiyong

    2016-01-01

    Well-defined biodegradable, pH-sensitive amphiphilic block polymers, poly(ethylene glycol)-Hyd-poly(lactic acid) (mPEG-Hyd-PLA) which have acid-cleavable linkages in their backbones, were synthesized via ring-opening polymerization initiated from hydrazone-containing macroinitiators. Introducing a hydrazone bond onto the backbone of an amphiphilic copolymer will find a broad-spectrum encapsulation of hydrophobic drugs. Dynamic light scattering (DLS) and transmission electron microscopy showed that the diblock copolymers self-assembled into stable micelles with average diameters of 100 nm. The mean diameters and size distribution of the hydrazone-containing micelles changed obviously in mildly acidic pH (multiple peaks from 1 to 202 nm appeared under a pH 4.0 condition) than in neutral, while there were no changes in the case of non-sensitive ones. Doxorubicin (DOX) and paclitaxel (PTX) were loaded with drug loading content ranging from 2.4 to 3.5 %, respectively. Interestingly, the anticancer drugs released from mPEG-Hyd-PLA micelles could also be promoted by the increased acidity. An in vitro cytotoxicity study showed that the DOX-loaded mPEG-Hyd-PLA micelles have significantly enhanced cytotoxicity against HepG2 cells compared with the non-sensitive poly(ethylene glycol)-block-poly(lactic acid) (mPEG-PLA) micelles. Confocal microscopy observation indicated that more DOX were delivered into the nuclei of cells following 6 or 12 h incubation with DOX-loaded mPEG-Hyd-PLA micelles. In vivo studies on H22-bearing Swiss mice demonstrated the superior anticancer activity of DOX-loaded mPEG-Hyd-PLA micelles over free DOX and DOX-loaded mPEG-PLA micelles. These hydrazone-containing pH-responsive degradable micelles provide a useful strategy for antitumor drug delivery.

  3. Polymeric Micelles as Novel Carriers for Poorly Soluble Drugs--A Review.

    Science.gov (United States)

    Reddy, B Pavan Kumar; Yadav, Hemant K S; Nagesha, Dattatri K; Raizaday, Abhay; Karim, Abdul

    2015-06-01

    Polymeric micelles are used as 'smart drug carriers' for targeting certain areas of the body by making them stimuli-sensitive or by attachment of a specific ligand molecule onto their surface. The main aim of using polymeric micelles is to deliver the poorly water soluble drugs. Now-a-days they are used especially in the areas of cancer therapy also. In this article we have reviewed several aspects of polymeric micelles concerning their mechanism of formation, chemical nature, preparation and characterization techniques, and their applications in the areas of drug delivery.

  4. 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.

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

    KAUST Repository

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

    2015-01-01

    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.

  6. Solvation dynamics in triton-X-100 and triton-X-165 micelles: Effect of micellar size and hydration

    Science.gov (United States)

    Kumbhakar, Manoj; Nath, Sukhendu; Mukherjee, Tulsi; Pal, Haridas

    2004-09-01

    Dynamic Stokes' shift measurements using coumarin 153 as the fluorescence probe have been carried out to study solvation dynamics in two nonionic micelles, viz., triton-X-100 (TX-100) and triton-X-165 (TX-165). In both the micelles, the solvent relaxation dynamics is biexponential in nature. While the fast solvation time τs1 is seen to be almost similar for both the micelles, the slow solvation time τs2 is found to be appreciably smaller in TX-165 than in TX-100 micelle. Dynamic light scattering measurements indicate that the TX-165 micelles are substantially smaller in size than that of TX-100. Assuming similar core size for both the micelles, as expected from the similar chemical structures of the nonpolar ends for both the surfactants, the Palisade layer is also indicated to be substantially thinner for TX-165 micelles than that of TX-100. The aggregation number of TX-165 micelles is also found to be substantially smaller than that of TX-100 micelles. Fluorescence spectral studies of C153 dye in the two micelles indicate that the Palisade layer of TX-165 micelles is more polar than that of TX-100 micelles. Fluorescence anisotropy measurements indicate that the microviscosity in the Palisade layer of TX-165 micelles is also lower than that of TX-100 micelles. Based on these results it is inferred that the structure of the Palisade layer of TX-165 micelles is quite loose and have higher degree hydration in comparison to that of TX-100 micelles. Due to these structural differences in the Palisade layers of TX-165 and TX-100 micelles the solvation dynamics is faster in the former micelles than in the latter. It has been further inferred that in the present systems the collective response of the water molecules at somewhat away from the probes is responsible for the faster component of the solvation time, which does not reflect much of the structural changes of the micellar Palisade layer. On the contrary, the slower solvation time component, which is mainly due to

  7. Structural investigations of sodium caseinate micelles in complex environments

    Energy Technology Data Exchange (ETDEWEB)

    Huck Iriart, C.; Herrera, M.L.; Candal, R. [Universidad de Buenos Aires, Buenos Aires (Argentina); Oliveira, C.L.P. [Universidade de Sao Paulo (USP), Sao Paulo, SP (Brazil); Torriani, I. [Laboratorio Nacional de Luz Sincrotron (LNLS), Campinas, SP (Brazil)

    2012-07-01

    Full text: The most frequent destabilization mechanisms in Sodium Caseinate (NaCas) emulsions are creaming and flocculation. Coarse or fine emulsions with low protein con- tent destabilize mainly by creaming. If migration mechanism is suppressed, flocculation may become the main mechanism of destabilization. Small Angle X-Ray Scattering (SAXS) technique was applied to investigate sodium caseinate micelles structure in different environments. As many natural products, Sodium Caseinate samples have large polydisperse size distribution. The experimental data was analyzed using advanced modeling approaches. The Form Factor for the Caseinate micelle subunits was described by an ellipsoidal core shell model and the structure factor was split into two contributions, one corresponding to the particle-particle interactions and another one for the long range correlation of the subunits in the supramolecular structure. For the first term the hard sphere structure factor using the Percus-Yevick approximation for closure relation was used and for the second term a fractal model was applied. Three concentrations of sodium Caseinate (2, 5 and 7.5 %wt.) were measured in pure water, sugar solutions (20 %wt.) and in three different lipid phase emulsions containing 10 %wt. sunflower seed, olive and fish oils. Data analysis provided an average casein subunit radius of 4 nm, an average distance between the subunits of around 20nm and a fractal dimension value of around 3 for all samples. As indicated by the values of the correlation lengths for the set of studied samples, the casein aggregation is strongly affected by simple sugar additions and it is enhanced by emulsion droplets hydrophobic interaction. As will be presented, these nanoscale structural results provided by scattering experiments is consistent with macroscopic results obtained from several techniques, providing a new understanding of NaCas emulsions. (author)

  8. Structural investigations of sodium caseinate micelles in complex environments

    International Nuclear Information System (INIS)

    Huck Iriart, C.; Herrera, M.L.; Candal, R.; Oliveira, C.L.P.; Torriani, I.

    2012-01-01

    Full text: The most frequent destabilization mechanisms in Sodium Caseinate (NaCas) emulsions are creaming and flocculation. Coarse or fine emulsions with low protein con- tent destabilize mainly by creaming. If migration mechanism is suppressed, flocculation may become the main mechanism of destabilization. Small Angle X-Ray Scattering (SAXS) technique was applied to investigate sodium caseinate micelles structure in different environments. As many natural products, Sodium Caseinate samples have large polydisperse size distribution. The experimental data was analyzed using advanced modeling approaches. The Form Factor for the Caseinate micelle subunits was described by an ellipsoidal core shell model and the structure factor was split into two contributions, one corresponding to the particle-particle interactions and another one for the long range correlation of the subunits in the supramolecular structure. For the first term the hard sphere structure factor using the Percus-Yevick approximation for closure relation was used and for the second term a fractal model was applied. Three concentrations of sodium Caseinate (2, 5 and 7.5 %wt.) were measured in pure water, sugar solutions (20 %wt.) and in three different lipid phase emulsions containing 10 %wt. sunflower seed, olive and fish oils. Data analysis provided an average casein subunit radius of 4 nm, an average distance between the subunits of around 20nm and a fractal dimension value of around 3 for all samples. As indicated by the values of the correlation lengths for the set of studied samples, the casein aggregation is strongly affected by simple sugar additions and it is enhanced by emulsion droplets hydrophobic interaction. As will be presented, these nanoscale structural results provided by scattering experiments is consistent with macroscopic results obtained from several techniques, providing a new understanding of NaCas emulsions. (author)

  9. 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.

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

    Science.gov (United States)

    Shi, Yanan; Sun, Fengying; Wang, Dan; Zhang, Renyu; Dou, Changlin; Liu, Wanhui; Sun, Kaoxiang; Li, Youxin

    2013-10-01

    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 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.

  11. Development and evaluation of N-naphthyl-N,O-succinyl chitosan micelles containing clotrimazole for oral candidiasis treatment.

    Science.gov (United States)

    Tonglairoum, Prasopchai; Woraphatphadung, Thisirak; Ngawhirunpat, Tanasait; Rojanarata, Theerasak; Akkaramongkolporn, Prasert; Sajomsang, Warayuth; Opanasopit, Praneet

    2017-03-01

    Clotrimazole (CZ)-loaded N-naphthyl-N,O-succinyl chitosan (NSCS) micelles have been developed as an alternative for oral candidiasis treatment. NSCS was synthesized by reductive N-amination and N,O-succinylation. CZ was incorporated into the micelles using various methods, including the dropping method, the dialysis method, and the O/W emulsion method. The size and morphology of the CZ-loaded micelles were characterized using dynamic light scattering measurements (DLS) and a transmission electron microscope (TEM), respectively. The drug entrapment efficiency, loading capacity, release characteristics, and antifungal activity against Candida albicans were also evaluated. The CZ-loaded micelles prepared using different methods differed in the size of micelles. The micelles ranged in size from 120 nm to 173 nm. The micelles prepared via the O/W emulsion method offered the highest percentage entrapment efficiency and loading capacity. The CZ released from the CZ-loaded micelles at much faster rate compared to CZ powder. The CZ-loaded NSCS micelles can significantly hinder the growth of Candida cells after contact. These CZ-loaded NSCS micelles offer great antifungal activity and might be further developed to be a promising candidate for oral candidiasis treatment.

  12. 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.

  13. Glucose-installed, SPIO-loaded PEG- b-PCL micelles as MR contrast agents to target prostate cancer cells

    Science.gov (United States)

    Theerasilp, Man; Sunintaboon, Panya; Sungkarat, Witaya; Nasongkla, Norased

    2017-11-01

    Polymeric micelles of poly(ethylene glycol)- block-poly(ɛ-caprolactone) bearing glucose analog encapsulated with superparamagnetic iron oxide nanoparticles (Glu-SPIO micelles) were synthesized as an MRI contrast agent to target cancer cells based on high-glucose metabolism. Compared to SPIO micelles (non-targeting SPIO micelles), Glu-SPIO micelles demonstrated higher toxicity to human prostate cancer cell lines (PC-3) at high concentration. Atomic absorption spectroscopy was used to determine the amount of iron in cells. It was found that the iron in cancer cells treated by Glu-SPIO micelles were 27-fold higher than cancer cells treated by SPIO micelles at the iron concentration of 25 ppm and fivefold at the iron concentration of 100 ppm. To implement Glu-SPIO micelles as a MR contrast agent, the 3-T clinical MRI was applied to determine transverse relaxivities ( r 2*) and relaxation rate (1/ T 2*) values. In vitro MRI showed different MRI signal from cancer cells after cellular uptake of SPIO micelles and Glu-SPIO micelles. Glu-SPIO micelles was highly sensitive with the r 2* in agarose gel at 155 mM-1 s-1. Moreover, the higher 1/ T 2* value was found for cancer cells treated with Glu-SPIO micelles. These results supported that glucose ligand increased the cellular uptake of micelles by PC-3 cells with over-expressing glucose transporter on the cell membrane. Thus, glucose can be used as a small molecule ligand for targeting prostate cancer cells overexpressing glucose transporter.

  14. Electron transfer reactions of ruthenium(II) complexes with polyphenolic acids in micelles

    Energy Technology Data Exchange (ETDEWEB)

    Rajeswari, Angusamy [School of Chemistry, Madurai Kamaraj University, Madurai 625 021 (India); Department of Chemistry, Fatima College, Madurai 625 018 (India); Ramdass, Arumugam [School of Chemistry, Madurai Kamaraj University, Madurai 625 021 (India); Research Department of Chemistry, Aditanar College of Arts and Science, Tiruchendur 628 216 (India); Muthu Mareeswaran, Paulpandian [School of Chemistry, Madurai Kamaraj University, Madurai 625 021 (India); Department of Industrial Chemistry, Alagappa University, Karaikudi 630 003 (India); Rajagopal, Seenivasan, E-mail: rajagopalseenivasan@yahoo.com [School of Chemistry, Madurai Kamaraj University, Madurai 625 021 (India)

    2016-02-15

    The electron transfer in a microhetrogeneous system is a perfect mimic of biological electron transfer. The electron transfer between biologically important phenolic acids and ruthenium (II) complexes is systematically studied in the presence of anionic and cationic micelles. The photophysical properties of these ruthenium (II) complexes with anionic and cationic micelles and their binding abilities with these two type of micelles are also studies using absorption, emission and excited state lifetime spectral techniques. Pseudophase Ion Exchange (PIE) Model is applied to derive mechanism of electron transfer in two types of micelles. - Highlights: • Effect of microhetrogeneous system is studied using ruthenium (II) complexes and gallic acid is studied. • Pseudophase Ion exchange model is applied to derive the mechanism. • Binding constants are in the range of 10{sup 2}–10{sup 4} M{sup −1}.

  15. HPMA-based polymeric micelles for curcumin solubilization and inhibition of cancer cell growth

    NARCIS (Netherlands)

    Naksuriya, Ornchuma; Shi, Yang; Van Nostrum, Cornelus F.|info:eu-repo/dai/nl/134498690; Anuchapreeda, Songyot; Hennink, Wim E.|info:eu-repo/dai/nl/070880409; Okonogi, Siriporn

    2015-01-01

    Abstract Curcumin (CM) has been reported as a potential anticancer agent. However, its pharmaceutical applications as therapeutic agent are hampered because of its poor aqueous solubility. The present study explores the advantages of polymeric micelles composed of block copolymers of

  16. The structure of the antimicrobial active center of lactoferricin B bound to sodium dodecyl sulfate micelles.

    Science.gov (United States)

    Schibli, D J; Hwang, P M; Vogel, H J

    1999-03-12

    Lactoferricin B (LfcinB) is a 25-residue antimicrobial peptide released from bovine lactoferrin upon pepsin digestion. The antimicrobial center of LfcinB consists of six residues (RRWQWR-NH2), and it possesses similar bactericidal activity to LfcinB. The structure of the six-residue peptide bound to sodium dodecyl sulfate (SDS) micelles has been determined by NMR spectroscopy and molecular dynamics refinement. The peptide adopts a well defined amphipathic structure when bound to SDS micelles with the Trp sidechains separated from the Arg residues. Additional evidence demonstrates that the peptide is oriented in the micelle such that the Trp residues are more deeply buried in the micelle than the Arg and Gln residues.

  17. Kappa-casein micelles: structure, interaction and gelling studied by small-angle neutron scattering.

    Science.gov (United States)

    de Kruif, C G; May, R P

    1991-09-01

    Small-angle neutron scattering (SANS) measurements on dilute and concentrated dispersions of kappa-casein micelles in a buffer at pH = 6.7 were made using the D11 diffractometer in Grenoble. Results indicate that the micelles have a dense core with a fluffy outer layer. This outer layer appears to give rise to a steeply repulsive interaction on contact. In fact, the hard-sphere model best fits the measured scattering intensities. Adding chymosin to the dispersion initiated a fractal flocculation of the micelles and consecutively a coalescence of the micelles. This unexpected second process resembled that of spinodal demixing. The dispersion phase thus separates into a water and a protein phase on a time scale of hours. The observed phenomona contribute to the understanding of the cheese-making process.

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

    Science.gov (United States)

    Qurie, Mohannad; Khamis, Mustafa; Manassra, Adnan; Ayyad, Ibrahim; Nir, Shlomo; Scrano, Laura; Bufo, Sabino A.; Karaman, Rafik

    2013-01-01

    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. PMID:24222757

  19. Effect of water on the local electric potential of simulated ionic micelles

    Energy Technology Data Exchange (ETDEWEB)

    Brodskaya, Elena N.; Vanin, Alexander A., E-mail: alexvanin@yandex.ru [Institute of Chemistry, St. Petersburg State University, Universitetskiy pr. 26, Petrodvoretz, St. Petersburg 198504 (Russian Federation)

    2015-07-28

    Ionic micelles in an aqueous solution containing single-charged counter-ions have been simulated by molecular dynamics. For both cationic and anionic micelles, it has been demonstrated that explicit description of solvent has strong effect on the micelle’s electric field. The sign of the local charge alters in the immediate vicinity of the micellar crown and the electric potential varies nonmonotonically. Two micelle models have been examined: the hybrid model with a rigid hydrocarbon core and the atomistic model. For three molecular models of water (Simple Point Charge model (SPC), Transferable Intermolecular Potential 5- Points (TIP5P) and two-centered S2), the results have been compared with those for the continuum solvent model. The orientational ordering of solvent molecules has strong effect on the local electric field surprisingly far from the micelle surface.

  20. Nanostructured oxygen sensor--using micelles to incorporate a hydrophobic platinum porphyrin.

    Directory of Open Access Journals (Sweden)

    Fengyu Su

    Full Text Available Hydrophobic platinum(II-5,10,15,20-tetrakis-(2,3,4,5,6-pentafluorophenyl-porphyrin (PtTFPP was physically incorporated into micelles formed from poly(ε-caprolactone-block-poly(ethylene glycol to enable the application of PtTFPP in aqueous solution. Micelles were characterized using dynamic light scattering (DLS and atomic force microscopy (AFM to show an average diameter of about 140 nm. PtTFPP showed higher quantum efficiency in micellar solution than in tetrahydrofuran (THF and dichloromethane (CH₂Cl₂. PtTFPP in micelles also exhibited higher photostability than that of PtTFPP suspended in water. PtTFPP in micelles exhibited good oxygen sensitivity and response time. This study provided an efficient approach to enable the application of hydrophobic oxygen sensors in a biological environment.

  1. Enhanced hydrogen production by coupled system of Halobacterium halobium and chloroplast after entrapment within reverse micelles

    Energy Technology Data Exchange (ETDEWEB)

    Singh, A.; Dubey, R.S. [Banaras Hindhu University, Varanasi (India). Dept. of Biochemistry; Pandey, K.D. [Banaras Hindhu University, Varanasi (India). Dept. of Botany

    1999-08-01

    Reverse micelles were used for the enhanced rate of photoproduction of hydrogen using the coupled system of Halobacterium halobium and chloroplasts organelles. Different combinations of organic solvents and surfactants were used for generating reverse micelles. A several fold enhancement in the rate of H{sub 2} production was observed when the coupled system was entrapped within reverse micelles as compared to the aqueous suspension where no detectable H{sub 2} was produced. The coupled system immobilized in reverse micelles formed by sodium lauryl sulfate and carbon tetrachloride yielded maximum rate of H{sub 2} evolution. The optimum temperature for such hydrogen production was 40{sup o}C using light of 520-570 nm wavelength and 100 lux intensity. (author)

  2. Structural study of concentrated micelle-solutions of sodium octanoate by light scattering

    International Nuclear Information System (INIS)

    Hayoun, Marc

    1982-05-01

    Structural investigation of sodium octanoate (CH 3 -(CH 2 ) 6 -COONa) by light scattering has been made to study properties of concentrated aqueous micelle-solutions. From static light scattering data, the micellar weight and shape have been determined. The monomer aggregation number and the apparent micellar charge have been confirmed. Quasi-elastic light scattering, has been used to measure the effective diffusion coefficient as a function of the volume fraction. Extrapolation to the c.m.c. give the hydrodynamic radius of the micelles. At low micelle-concentration, strong exchange reaction between monomers and micelles affects the Brownian motion and resulting is an increase in the diffusion coefficient. The experimental data show a strong hydrodynamic contribution to S(q) (factor structure) and D(q) (effective diffusion coefficient) arising from hard spheres interactions with a large repulsive potential. (author) [fr

  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 substitution on aniline in inducing growth of anionic micelles

    International Nuclear Information System (INIS)

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

    2004-01-01

    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, o-toluidine hydrochloride and m-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. (author)

  5. Effect of calcium chelators on physical changes in casein micelles in concentrated micellar casein solutions

    NARCIS (Netherlands)

    Kort, de E.J.P.; Minor, M.; Snoeren, T.H.M.; Hooijdonk, van A.C.M.; Linden, van der E.

    2011-01-01

    The effect of calcium chelators on physical changes of casein micelles in concentrated micellar casein solutions was investigated by measuring calcium-ion activity, viscosity and turbidity, and performing ultracentrifugation. The highest viscosities were measured on addition of sodium

  6. Influence of serum albumin on intracellular delivery of drug-loaded hyaluronan polymeric micelles

    Czech Academy of Sciences Publication Activity Database

    Nešporová, K.; Sogorková, J.; Smejkalova, D.; Kulhánek, J.; Huerta-Angeles, G.; Kubala, Lukáš; Velebný, V.

    2016-01-01

    Roč. 511, č. 1 (2016), s. 638-647 ISSN 0378-5173 Institutional support: RVO:68081707 Keywords : Polymeric micelle * Hyaluronan * Fatty acid Subject RIV: BO - Biophysics Impact factor: 3.649, year: 2016

  7. Curcumin-loaded chitosan-cholesterol micelles: evaluation in monolayers and 3D cancer spheroid model.

    Science.gov (United States)

    Muddineti, Omkara Swami; Kumari, Preeti; Ray, Eupa; Ghosh, Balaram; Biswas, Swati

    2017-06-02

    To improve the bioavailability and anticancer potential of curcumin by using a cholesterol-conjugated chitosan micelle. Methods & methods: Cholesterol was conjugated to chitosan (15 kDa) to form self-assembled micelles, which loaded curcumin. Physicochemical characterization and formulation optimization of the drug-loaded micelles (curcumin-loaded chitosan-cholesterol micelles [C-CCM]) were performed. In vitro cellular uptake and viability of C-CCM were investigated in melanoma and breast cancer cell lines. The antitumor efficacy was evaluated in 3D lung cancer spheroid model. The optimized C-CCM had size of approximately 162 nm with loading efficiency of approximately 36%. C-CCM was taken up efficiently by the cells, and it reduced cancer cell viability significantly compared with free curcumin. C-CCM enhanced the antitumor efficacy in spheroids, suggesting that C-CCM could be used as an effective chemotherapy in cancer.

  8. Micelle formation during extraction of alkali elements from strongly alkaline mediums

    International Nuclear Information System (INIS)

    Apanasenko, V.V.; Reznik, A.M.; Bukin, V.I.; Brodskaya, A.V.

    1988-01-01

    Extraction of potassium, rubidium and cesium by phenol reagents in hydrocarbon solvents from strongly alkakine solutions was considered. Tendency of prepared alkali metal phenolates to form micelles in aqueous and organic phases was revealed. Phenolates tendency to form micelles is dictated mainly by the size and position of hydrocarbon substituent in molecule. It is shown that when micelles form in organic phase, alkali elements can be extracted both according to cation-exchange mechanism and according to micellar one. It is noted that alkai element extraction from strongly alkaline media requires the correct choice of extractant: alkali metal phenolate shouldn't form micelles in aqueous solution. n-Alkyl- and arylphenoldisulfides and polysulfides are most preferable for solvent extraction among considered phenol derivatives

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

    Directory of Open Access Journals (Sweden)

    Liu Y

    2016-07-01

    Full Text Available Yuling Liu,1,* Yingqi Xu,2,* Minghui Wu,3 Lijiao Fan,1 Chengwei He,2 Jian-Bo Wan,2 Peng Li,2 Meiwan Chen,2 Hui Li11Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 2State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, People’s Republic of China; 3Department of Cell Biology and Anatomy, School of Medicine, University of Florida, Gainesville, FL, USA *These authors contributed equally to this work Abstract: 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. Keywords: F68, vitamin E

  10. 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

  11. Controlling the Size and Shape of the Elastin-Like Polypeptide based Micelles

    Science.gov (United States)

    Streletzky, Kiril; Shuman, Hannah; Maraschky, Adam; Holland, Nolan

    Elastin-like polypeptide (ELP) trimer constructs make reliable environmentally responsive micellar systems because they exhibit a controllable transition from being water-soluble at low temperatures to aggregating at high temperatures. It has been shown that depending on the specific details of the ELP design (length of the ELP chain, pH and salt concentration) micelles can vary in size and shape between spherical micelles with diameter 30-100 nm to elongated particles with an aspect ratio of about 10. This makes ELP trimers a convenient platform for developing potential drug delivery and bio-sensing applications as well as for understanding micelle formation in ELP systems. Since at a given salt concentration, the headgroup area for each foldon should be constant, the size of the micelles is expected to be proportional to the volume of the linear ELP available per foldon headgroup. Therefore, adding linear ELPs to a system of ELP-foldon should result in changes of the micelle volume allowing to control micelle size and possibly shape. The effects of addition of linear ELPs on size, shape, and molecular weight of micelles at different salt concentrations were studied by a combination of Dynamic Light Scattering and Static Light Scattering. The initial results on 50 µM ELP-foldon samples (at low salt) show that Rh of mixed micelles increases more than 5-fold as the amount of linear ELP raised from 0 to 50 µM. It was also found that a given mixture of linear and trimer constructs has two temperature-based transitions and therefore displays three predominant size regimes.

  12. Influence of gold nanoparticles of varying size in improving the lipase activity within cationic reverse micelles.

    Science.gov (United States)

    Maiti, Subhabrata; Das, Dibyendu; Shome, Anshupriya; Das, Prasanta Kumar

    2010-02-08

    Herein, we report the effect of gold nanoparticles (GNPs) in enhancing lipase activity in reverse micelles of cetyltrimethylammonium bromide (CTAB)/water/isooctane/n-hexanol. The size and concentration of the nanoparticles were varied and their specific roles were assessed in detail. An overall enhancement of activity was observed in the GNP-doped CTAB reverse micelles. The improvement in activity becomes more prominent with increasing concentration and size of the GNPs (0-52 microM and ca. 3-30 nm, respectively). The observed highest lipase activity (k(2)=1070+/-12 cm(3) g(-1) s(-1)) in GNP-doped CTAB reverse micelles ([GNP]: 52 microm, ca. 20 nm) is 2.5-fold higher than in CTAB reverse micelles without GNPs. Improvement in the lipase activity is only specific to the GNP-doped reverse micellar media, whereas GNP deactivates and structurally deforms the enzyme in aqueous media. The reason for this activation is probably due to the formation of larger-sized reverse micelles in which the GNP acts as a polar core and the surfactants aggregate around the nanoparticle ('GNP pool') instead of only water. Lipase at the augmented interface of the GNP-doped reverse micelle showed improved activity because of enhancement in both the substrate and enzyme concentrations and increased flexibility in the lipase conformation. The extent of the activation is greater in the case of the larger-sized GNPs. A correlation has been established between the activity of lipase and its secondary structure by using circular dichroism and FTIR spectroscopic analysis. The generalized influence of GNP is verified in the reverse micelles of another surfactant, namely, cetyltripropylammonium bromide (CTPAB). TEM, dynamic light scattering (DLS), and UV/Vis spectroscopic analysis were utilized to characterize the GNPs and the organized aggregates. For the first time, CTAB-based reverse micelles have been found to be an excellent host for lipase simply by doping with appropriately sized GNPs.

  13. 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. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  14. Patchy micelles based on coassembly of block copolymer chains and block copolymer brushes on silica particles.

    Science.gov (United States)

    Zhu, Shuzhe; Li, Zhan-Wei; Zhao, Hanying

    2015-04-14

    Patchy particles are a type of colloidal particles with one or more well-defined patches on the surfaces. The patchy particles with multiple compositions and functionalities have found wide applications from the fundamental studies to practical uses. In this research patchy micelles with thiol groups in the patches were prepared based on coassembly of free block copolymer chains and block copolymer brushes on silica particles. Thiol-terminated and cyanoisopropyl-capped polystyrene-block-poly(N-isopropylacrylamide) block copolymers (PS-b-PNIPAM-SH and PS-b-PNIPAM-CIP) were synthesized by reversible addition-fragmentation chain transfer polymerization and chemical modifications. Pyridyl disulfide-functionalized silica particles (SiO2-SS-Py) were prepared by four-step surface chemical reactions. PS-b-PNIPAM brushes on silica particles were prepared by thiol-disulfide exchange reaction between PS-b-PNIPAM-SH and SiO2-SS-Py. Surface micelles on silica particles were prepared by coassembly of PS-b-PNIPAM-CIP and block copolymer brushes. Upon cleavage of the surface micelles from silica particles, patchy micelles with thiol groups in the patches were obtained. Dynamic light scattering, transmission electron microscopy, and zeta-potential measurements demonstrate the preparation of patchy micelles. Gold nanoparticles can be anchored onto the patchy micelles through S-Au bonds, and asymmetric hybrid structures are formed. The thiol groups can be oxidized to disulfides, which results in directional assembly of the patchy micelles. The self-assembly behavior of the patchy micelles was studied experimentally and by computer simulation.

  15. Novel spirotetracyclic zwitterionic dual H(1)/5-HT(2A) receptor antagonists for the treatment of sleep disorders.

    Science.gov (United States)

    Gianotti, Massimo; Botta, Maurizio; Brough, Stephen; Carletti, Renzo; Castiglioni, Emiliano; Corti, Corrado; Dal-Cin, Michele; Delle Fratte, Sonia; Korajac, Denana; Lovric, Marija; Merlo, Giancarlo; Mesic, Milan; Pavone, Francesca; Piccoli, Laura; Rast, Slavko; Roscic, Maja; Sava, Anna; Smehil, Mario; Stasi, Luigi; Togninelli, Andrea; Wigglesworth, Mark J

    2010-11-11

    Histamine H(1) and serotonin 5-HT(2A) receptors mediate two different mechanisms involved in sleep regulation: H(1) antagonists are sleep inducers, while 5-HT(2A) antagonists are sleep maintainers. Starting from 9'a, a novel spirotetracyclic compound endowed with good H(1)/5-HT(2A) potency but poor selectivity, very high Cli, and a poor P450 profile, a specific optimization strategy was set up. In particular, we investigated the possibility of introducing appropriate amino acid moieties to optimize the developability profile of the series. Following this zwitterionic approach, we were able to identify several advanced leads (51, 65, and 73) with potent dual H(1)/5-HT(2A) activity and appropriate developability profiles. These compounds exhibited efficacy as hypnotic agents in a rat telemetric sleep model with minimal effective doses in the range 3-10 mg/kg po.

  16. Zwitterionic peptide anchored to conducting polymer PEDOT for the development of antifouling and ultrasensitive electrochemical DNA sensor.

    Science.gov (United States)

    Wang, Guixiang; Han, Rui; Su, Xiaoli; Li, Yinan; Xu, Guiyun; Luo, Xiliang

    2017-06-15

    Zwitterionic peptides were anchored to a conducting polymer of citrate doped poly(3,4-ethylenedioxythiophene) (PEDOT) via the nickel cation coordination, and the obtained peptide modified PEDOT, with excellent antifouling ability and good conductivity, was further used for the immobilization of a DNA probe to construct an electrochemical biosensor for the breast cancer marker BRCA1. The DNA biosensor was highly sensitive (with detection limit of 0.03fM) and selective, and it was able to detect BRCA1 in 5% (v/v) human plasma with satisfying accuracy and low fouling. The marriage of antifouling and biocompatible peptides with conducting polymers opened a new avenue to construct electrochemical biosensors capable of assaying targets in complex biological media with high sensitivity and without biofouling. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Light-switchable polymer from cationic to zwitterionic form: synthesis, characterization, and interactions with DNA and bacterial cells.

    Science.gov (United States)

    Sobolčiak, Patrik; Spírek, Mário; Katrlík, Jaroslav; Gemeiner, Peter; Lacík, Igor; Kasák, Peter

    2013-04-25

    A novel cationic polymer poly(N,N-dimethyl-N-[3-(methacroylamino) propyl]-N-[2-[(2-nitrophenyl)methoxy]-2-oxo-ethyl]ammonium chloride) is synthesized by free-radical polymerization of N-[3-(dimethylamino)propyl] methacrylamide and subsequent quaternization with o-nitrobenzyl 2-chloroacetate. The photolabile o-nitrobenzyl carboxymethyl pendant moiety is transformed to the zwitterionic carboxybetaine form upon the irradiation at 365 nm. This feature is used to condense and, upon the light irradiation, to release double-strand DNA tested by gel electrophoresis and surface plasmon resonance experiments as well as to switch the antibacterial activity to non-toxic character demonstrated for Escherichia coli bacterial cells in solution and at the surface using the self-assembled monolayers. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Ultra-low fouling and high antibody loading zwitterionic hydrogel coatings for sensing and detection in complex media.

    Science.gov (United States)

    Chou, Ying-Nien; Sun, Fang; Hung, Hsiang-Chieh; Jain, Priyesh; Sinclair, Andrew; Zhang, Peng; Bai, Tao; Chang, Yung; Wen, Ten-Chin; Yu, Qiuming; Jiang, Shaoyi

    2016-08-01

    For surface-based diagnostic devices to achieve reliable biomarker detection in complex media such as blood, preventing nonspecific protein adsorption and incorporating high loading of biorecognition elements are paramount. In this work, a novel method to produce nonfouling zwitterionic hydrogel coatings was developed to achieve these goals. Poly(carboxybetaine acrylamide) (pCBAA) hydrogel thin films (CBHTFs) prepared with a carboxybetaine diacrylamide crosslinker (CBAAX) were coated on gold and silicon dioxide surfaces via a simple spin coating process. The thickness of CBHTFs could be precisely controlled between 15 and 150nm by varying the crosslinker concentration, and the films demonstrated excellent long-term stability. Protein adsorption from undiluted human blood serum onto the CBHTFs was measured with surface plasmon resonance (SPR). Hydrogel thin films greater than 20nm exhibited ultra-low fouling (crosslinked, purely zwitterionic, carboxybetaine thin film hydrogel (CBHTF) coating platform. The CBHTF on a hydrophilic surface demonstrated long-term stability. By varying the crosslinker content in the spin-coated hydrogel solution, the thickness of CBHTFs could be precisely controlled. Optimized CBHTFs exhibited ultra-low nonspecific protein adsorption below 5ng/cm(2) measured by a surface plasmon resonance (SPR) sensor, and their 3D architecture allowed antibody loading to reach 693ng/cm(2). This strategy provides a facile method to modify SPR biosensor chips with an advanced nonfouling material, and can be potentially expanded to a variety of implantable medical devices and diagnostic biosensors. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  19. In Situ Synthesis of Antimicrobial Silver Nanoparticles within Antifouling Zwitterionic Hydrogels by Catecholic Redox Chemistry for Wound Healing Application.

    Science.gov (United States)

    GhavamiNejad, Amin; Park, Chan Hee; Kim, Cheol Sang

    2016-03-14

    A multifunctional hydrogel that combines the dual functionality of both antifouling and antimicrobial capacities holds great potential for many bioapplications. Many approaches and different materials have been employed to synthesize such a material. However, a systematic study, including in vitro and in vivo evaluation, on such a material as wound dressings is highly scarce at present. Herein, we report on a new strategy that uses catecholic chemistry to synthesize antimicrobial silver nanoparticles impregnated into antifouling zwitterionic hydrogels. For this purpose, hydrophobic dopamine methacrylamide monomer (DMA) was mixed in an aqueous solution of sodium tetraborate decahydrate and DMA monomer became soluble after increasing pH to 9 due to the complexation between catechol groups and boron. Then, cross-linking polymerization of zwitterionic monomer was carried out with the solution of the protected dopamine monomer to produce a new hydrogel. When this new hydrogel comes in contact with a silver nitrate solution, silver nanoparticles (AgNPs) are formed in its structure as a result of the redox property of the catechol groups and in the absence of any other external reducing agent. The results obtained from TEM and XRD measurements indicate that AgNPs with diameters of around 20 nm had formed within the networks. FESEM images confirmed that the silver nanoparticles were homogeneously incorporated throughout the hydrogel network, and FTIR spectroscopy demonstrated that the catechol moiety in the polymeric backbone of the hydrogel is responsible for the reduction of silver ions into the AgNPs. Finally, the in vitro and in vivo experiments suggest that these mussel-inspired, antifouling, antibacterial hydrogels have great potential for use in wound healing applications.

  20. Synthesis and Solution Properties of Zwitterionic Copolymer of Acrylamide with 3-[(2-Acrylamido)dimethylammonio]propanesulfonate

    Energy Technology Data Exchange (ETDEWEB)

    Xiao, Hui; Hu, Jing; Jin, Shuailin; Li, Rui Hai [Sichuan Univ., Chengdu (China)

    2013-09-15

    A novel zwitterionic monomer 3-[(2-acrylamido)dimethylammonio]propanesulfonate (DMADAS) was designed and synthesized in this study. Then it was polymerized with acrylamide (AM) by free radical polymerization in 0.5 mol/L NaCl solution with ammonium persulfate ((NH{sub 4}){sub 2}S{sub 2}O{sub 8}) and sodium sulfate (NaHSO{sub 3}) as initiator. The structure and composition of DMADAS and acrylamide-3-[(2-acrylamido)-dimethylammonio]propanesulfonate copolymer (P-AM-DMADAS) were characterized by FT-IR spectroscopy, {sup 1}H NMR and elemental analyses. Isoelectric point (IEP) of P-AM-DMADAS was tested by nanoparticle size and potential analyzer. Solution properties of copolymer were studied by reduced viscosity. Antipolyelectrolyte behavior was observed and was found to be enhanced with increasing DMADAS content in copolymer. The results showed that the viscosity of P-AM-DMADAS is 5.472 dl/g in pure water. Electrolyte was added, which weakened the mutual attraction between sulfonic acid group and quaternary ammonium group. The conformation became loose, which led to the increase of reduced viscosity. The ability of monovalent and divalent cation influencing the viscosity of zwitterionic copolymer obeyed the following sequence: Li{sup +} < Na{sup +} < K{sup +}, Mg{sup 2+} < Ca{sup 2+} < Ba{sup 2+}, and that of anion is in the order: Cl{sup -} < Br{sup -} < I{sup -}, CO{sub 3}{sup 2-} > SO{sub 3}{sup 2-} ≅ SO{sub 4}{sup 2-}.

  1. Development of lycopene micelle and lycopene chylomicron and a comparison of bioavailability

    International Nuclear Information System (INIS)

    Chen, Yi Jyun; Inbaraj, Baskaran Stephen; Chen, Bing Huei; Pu, Yeong Shiau

    2014-01-01

    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. (paper)

  2. Amphiphilic polymeric micelles as the nanocarrier for peroral delivery of poorly soluble anticancer drugs.

    Science.gov (United States)

    Tian, Ye; Mao, Shirui

    2012-06-01

    Many amphiphilic copolymers have recently been synthesized as novel promising micellar carriers for the delivery of poorly water-soluble anticancer drugs. Studies on the formulation and oral delivery of such micelles have demonstrated their efficacy in enhancing drug uptake and absorption, and exhibit prolonged circulation time in vitro and in vivo. In this review, literature on hydrophobic modifications of several hydrophilic polymers, including polyethylene glycol, chitosan, hyaluronic acid, pluronic and tocopheryl polyethylene glycol succinate, is summarized. Parameters influencing the properties of polymeric micelles for oral chemotherapy are discussed and strategies to overcome main barriers for polymeric micelles peroral absorption are proposed. During the design of polymeric micelles for peroral chemotherapy, selecting or synthesizing copolymers with good compatibility with the drug is an effective strategy to increase drug loading and encapsulation efficiency. Stability of the micelles can be improved in different ways. It is recommended to take permeability, mucoadhesion, sustained release, and P-glycoprotein inhibition into consideration during copolymer preparation or to consider adding some excipients in the formulation. Furthermore, both the copolymer structure and drug loading methods should be controlled in order to get micelles with appropriate particle size for better absorption.

  3. Combined photothermo-chemotherapy using gold nanoshells on drug-loaded micelles for colorectal cancer treatment

    Science.gov (United States)

    Lee, Shin-Yu; Shieh, Ming-Jium

    2018-02-01

    Combined photothermo-chemotherapy is a new strategy for cancer treatment which improves the therapeutic outcome by synergistic effects of both therapies. Here, we presented a multifunctional gold nanoshell that exhibited excellent photothermal conversion and delivered the hydrophobic chemotherapy drug, SN-38. The positively charged SN-38-loaded PDMA-PCL micelles were decorated with a gold layer by in situ reduction of chloroauric acid on the surface of micelles. Scanning and transmission electron microscopy images proved micelles were successfully decorated and the resulting gold nanoshells had a spherical morphology with a narrow size distribution. The synthesized gold nanoshells displayed a broad surface plasmon resonance peak in the near-infrared wavelength region and a great photothermal conversion ability. After pegylation, gold nanoshells were stable in biological media and appeared highly biocompatible in the absence of laser irradiation. Upon near-infrared laser irradiation, incident energy was converted into heat by gold nanoshells on SN-38-loaded micelles (SN-38@pGNS), which causes local temperature increase and triggers the release of encapsulated drug. Compared to SN-38, SN-38-loaded micelles, or laser with drug-free gold nanoshells alone, combined photothermo-chemotherapy using SN-38@pGNS with laser irradiation killed colorectal cancer cells with higher efficacy in vitro and demonstrated significant tumor suppression in vivo, suggesting that gold nanoshells on drug-loaded micelles delivered SN-38 and photothermal therapy in synergistic actions and might be a potential candidate for future colorectal cancer therapy.

  4. Cryo-transmission electron tomography of native casein micelles from bovine milk

    Science.gov (United States)

    Trejo, R.; Dokland, T.; Jurat-Fuentes, J.; Harte, F.

    2013-01-01

    Caseins are the principal protein components in milk and an important ingredient in the food industry. In liquid milk, caseins are found as micelles of casein proteins and colloidal calcium nanoclusters. Casein micelles were isolated from raw skim milk by size exclusion chromatography and suspended in milk protein-free serum produced by ultrafiltration (molecular weight cut-off of 3 kDa) of raw skim milk. The micelles were imaged by cryo-electron microscopy and subjected to tomographic reconstruction methods to visualize the 3-dimensional and internal organization of native casein micelles. This provided new insights into the internal architecture of the casein micelle that had not been apparent from prior cryo-transmission electron microscopy studies. This analysis demonstrated the presence of water-filled cavities (~20 to 30 nm in diameter), channels (diameter greater than ~5 nm), and several hundred high-density nanoclusters (6 to 12 nm in diameter) within the interior of the micelles. No spherical protein submicellar structures were observed. PMID:22118067

  5. Light-responsive micelles of spiropyran initiated hyperbranched polyglycerol for smart drug delivery.

    Science.gov (United States)

    Son, Suhyun; Shin, Eeseul; Kim, Byeong-Su

    2014-02-10

    Light-responsive polymeric micelles have emerged as site-specific and time-controlled systems for advanced drug delivery. Spiropyran (SP), a well-known photochromic molecule, was used to initiate the ring-opening multibranching polymerization of glycidol to afford a series of hyperbranched polyglycerols (SP-hb-PG). The micelle assembly and disassembly were induced by an external light source owing to the reversible photoisomerization of hydrophobic SP to hydrophilic merocyanine (MC). Transmission electron microscopy, atomic force microscopy, UV/vis spectroscopy, and dynamic light scattering demonstrated the successful assembly and disassembly of SP-hb-PG micelles. In addition, the critical micelle concentration (CMC) was determined through the fluorescence analysis of pyrene to confirm the amphiphilicity of respective SP-hb-PGn (n = 15, 29, and 36) micelles, with CMC values ranging from 13 to 20 mg/L, which is correlated to the length of the polar polyglycerol backbone. Moreover, the superior biocompatibility of the prepared SP-hb-PG was evaluated using WI-38 cells and HeLa cells, suggesting the prospective applicability of the micelles in smart drug delivery systems.

  6. Titration calorimetry of surfactant–drug interactions: Micelle formation and saturation studies

    International Nuclear Information System (INIS)

    Waters, Laura J.; Hussain, Talib; Parkes, Gareth M.B.

    2012-01-01

    Highlights: ► Isothermal titration calorimetry can be used to monitor the saturation of micelles with pharmaceutical compounds. ► The number of drug molecules per micelle varies depending on the drug used and the temperature of the calorimeter. ► The change in enthalpy for the saturation of micelles with drugs can be endothermic or exothermic. ► The critical micellar concentration of an anionic surfactant (SDS) does not appear to vary in the presence of drugs. - Abstract: Isothermal titration calorimetry (ITC) was employed to monitor the addition of five model drugs to anionic surfactant based micelles, composed of sodium dodecyl sulfate (SDS), through to the point at which they were saturated with drug. Analysis of the resultant data using this newly developed method has confirmed the suitability of the technique to acquire such data with saturation limits established in all cases. Values for the point at which saturation occurred ranged from 17 molecules of theophylline per micelle at T = 298 K up to 63 molecules of caffeine per micelle at 310 K. Micellar systems can be disrupted by the presence of additional chemicals, such as the drugs used in this study, therefore a separate investigation was undertaken to determine the critical micellar concentration (CMC) for SDS in the presence of each drug at T = 298 K and 310 K using ITC. In the majority of cases, there was no appreciable alteration to the CMC of SDS with drug present.

  7. 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.

  8. Complete regression of xenograft tumors using biodegradable mPEG-PLA-SN38 block copolymer micelles.

    Science.gov (United States)

    Lu, Lu; Zheng, Yan; Weng, Shuqiang; Zhu, Wenwei; Chen, Jinhong; Zhang, Xiaomin; Lee, Robert J; Yu, Bo; Jia, Huliang; Qin, Lunxiu

    2016-06-01

    7-Ethyl-10-hydroxy-comptothecin (SN38) is an active metabolite of irinotecan (CPT-11) and the clinical application of SN38 is limited by its hydrophobicity and instability. To address these issues, a series of novel amphiphilic mPEG-PLA-SN38-conjugates were synthesized by linking SN38 to mPEG-PLA-SA, and they could form micelles by self-assembly. The effects of mPEG-PLA composition were studied in vitro and in vivo. The mean diameters of mPEG2K-PLA-SN38 micelles and mPEG4K-PLA-SN38 micelles were 10-20nm and 120nm, respectively, and mPEG2K-PLA-SN38 micelles showed greater antitumor efficacy than mPEG4K-PLA-SN38 micelles both in vitro and in vivo. These data suggest that the lengths of mPEG and PLA chains had a major impact on the physicochemical characteristics and antitumor activity of SN38-conjugate micelles. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Evaluation of eco-friendly zwitterionic detergents for enveloped virus inactivation.

    Science.gov (United States)

    Conley, Lynn; Tao, Yinying; Henry, Alexis; Koepf, Edward; Cecchini, Douglas; Pieracci, John; Ghose, Sanchayita

    2017-04-01

    Inclusion of a detergent in protein biotherapeutic purification processes is a simple and very robust method for inactivating enveloped viruses. The detergent Triton X-100 has been used for many years and is part of the production process of several commercial therapeutic proteins. However, recent ecological studies have suggested that Triton X-100 and its break-down products can potentially behave as endocrine disrupters in aquatic organisms, raising concerns from an environmental impact perspective. As such, discharge of Triton X-100 into the waste water treatment plants is regulated in some jurisdictions, and alternative detergents for viral inactivation are required. In this work, we report on the identification and evaluation of more eco-friendly detergents as viable replacements for Triton X-100. Five detergent candidates with low to moderate environmental impact were initially identified and evaluated with respect to protein stability, followed by proof-of-concept virus inactivation studies using a model enveloped virus. From the set of candidates lauryldimethylamine N-oxide (LDAO) was identified as the most promising detergent due to its low ecotoxicity, robust anti-viral activity (LRV >4 at validation set-point conditions with X-MuLX), and absence of any negative impact on protein function. This detergent exhibited effective and robust virus inactivation in a broad range of protein concentrations, solution conductivities, pHs, and in several different cell culture fluid matrices. The only process parameter which correlated with reduced virus inactivation potency was LDAO concentration, and then only when the concentration was reduced to below the detergent's critical micelle concentration (CMC). Additionally, this work also demonstrated that LDAO was cleared to below detectable levels after Protein A affinity chromatography, making it suitable for use in a platform process that utilizes this chromatographic mode for protein capture. All these findings

  10. Pharmacokinetics and in vivo delivery of curcumin by copolymeric mPEG-PCL micelles.

    Science.gov (United States)

    Kheiri Manjili, Hamidreza; Ghasemi, Parisa; Malvandi, Hojjat; Mousavi, Mir Sajjad; Attari, Elahe; Danafar, Hossein

    2017-07-01

    Curcumin (CUR) has been associated with anti-inflammatory, antimicrobial, antioxidant, anti-amyloid, and antitumor effects, but its application is limited because of its low aqueous solubility and poor oral bioavailability. To progress the bioavailability and water solubility of CUR, we synthesized five series of mono methoxy poly (ethylene glycol)-poly (ε-caprolactone) (mPEG-PCL) diblock copolymers. The structure of the copolymers was characterized by H NMR, FTIR, DSC and GPC techniques. In this study, CUR was encapsulated within micelles through a single-step nano-precipitation method, leading to formation of CUR-loaded mPEG-PCL (CUR/mPEG-PCL) micelles. The resulting micelles were characterized further by various techniques such as dynamic light scattering (DLS) and atomic force microscopy (AFM). The cytotoxicity of void CUR, mPEG-PCL and CUR/mPEG-PCL micelles was compared to each other by performing MTT assay of the treated MCF-7 and 4T1 cell line. Study of the in vivo pharmacokinetics of the CUR-loaded micelles was also carried out on selected copolymers in comparison with CUR solution formulations. The results showed that the zeta potential of CUR-loaded micelles was about -11.5mV and the average size was 81.0nm. CUR was encapsulated into mPEG-PCL micelles with loading capacity of 20.65±0.015% and entrapment efficiency of 89.32±0.34%. The plasma AUC (0-t), t 1/2 and C max of CUR micelles were increased by 52.8, 4.63 and 7.51-fold compared to the CUR solution, respectively. In vivo results showed that multiple injections of CUR-loaded micelles could prolong the circulation time and increase the therapeutic efficacy of CUR. These results suggested that mPEG-PCL micelles would be a potential carrier for CUR. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Chemotherapeutic Effect of CD147 Antibody-labeled Micelles Encapsulating Doxorubicin Conjugate Targeting CD147-Expressing Carcinoma Cells.

    Science.gov (United States)

    Asakura, Tadashi; Yokoyama, Masayuki; Shiraishi, Koichi; Aoki, Katsuhiko; Ohkawa, Kiyoshi

    2018-03-01

    CD147 (basigin/emmprin) is expressed on the surface of carcinoma cells. For studying the efficacy of CD147-targeting medicine on CD147-expressing cells, we studied the effect of anti-CD147-labeled polymeric micelles (CD147ab micelles) that encapsulated a conjugate of doxorubicin with glutathione (GSH-DXR), with specific accumulation and cytotoxicity against CD147-expressing A431 human epidermoid carcinoma cells, Ishikawa human endometrial adenocarcinoma cells, and PC3 human prostate carcinoma cells. By treatment of each cell type with CD147ab micelles for 1 h, a specific accumulation of CD147ab micelles in CD147-expressing cells was observed. In addition, the cytotoxicity of GSH-DXR-encapsulated micelles against each cell type was measured by treatment of the micelles for 1 h. The cytotoxic effect of CD147ab micelles carrying GSH-DXR was 3- to 10-fold higher for these cells than that of micelles without GSH-DXR. These results suggest that GSH-DXR-encapsulated CD147ab micelles could serve as an effective drug delivery system to CD147-expressing carcinoma cells. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  12. Loading and release mechanisms of a biocide in polystyrene-block-poly(acrylic acid) block copolymer micelles.

    Science.gov (United States)

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

    2008-07-24

    The kinetics of loading of polystyrene197-block-poly(acrylic acid)47 (PS197-b-PAA47) micelles, suspended in water, with thiocyanomethylthiobenzothiazole biocide and its subsequent release were investigated. Loading of the micelles was found to be a two-step process. First, the surface of the PS core of the micelles is saturated with biocide, with a rate determined by the transfer of solid biocide to micelles during transient micelle-biocide contacts. Next, the biocide penetrates as a front into the micelles, lowering the Tg in the process (non-Fickian case II diffusion). The slow rate of release is governed by the height of the energy barrier that a biocide molecule must overcome to pass from PS into water, resulting in a uniform biocide concentration within the micelle, until Tg is increased to the point that diffusion inside the micelles becomes very slow. Maximum loading of biocide into micelles is approximately 30% (w/w) and is achieved in 1 h. From partition experiments, it can be concluded that the biocide has a similar preference for polystyrene as for ethylbenzene over water, implying that the maximum loading is governed by thermodynamics.

  13. Improved oral bioavailability and therapeutic efficacy of dabigatran etexilate via Soluplus-TPGS binary mixed micelles system.

    Science.gov (United States)

    Hu, Mei; Zhang, Jinjie; Ding, Rui; Fu, Yao; Gong, Tao; Zhang, Zhirong

    2017-04-01

    The clinical use of dabigatran etexilate (DABE) is limited by its poor absorption and relatively low bioavailability. Our study aimed to explore the potential of a mixed micelle system composed of Soluplus ® and D-alpha tocopheryl polyethylene glycol 1000 succinate (TPGS) to improve the oral absorption and bioavailability of DBAE. DBAE was first encapsulated into Soluplus/TPGS mixed micelles by a simple thin film hydration method. The DBAE loaded micelles displayed an average size distribution of around 83.13 nm. The cellular uptake of DBAE loaded micelles in Caco-2 cell monolayer was significantly enhanced by 2-2.6 fold over time as compared with DBAE suspension. Both lipid raft/caveolae and macropinocytosis-mediated the cell uptake of DBAE loaded micelles through P-glycoprotein (P-gp)-independent pathway. Compared with the DBAE suspension, the intestinal absorption of DBAE from DBAE mixed micelles in rats was significantly improved by 8 and 5-fold in ileum at 2 h and 4 h, respectively. Moreover, DBAE mixed micelles were absorbed into systemic circulation via both portal vein and lymphatic pathway. The oral bioavailability of DBAE mixed micelles in rats was 3.37 fold higher than that of DBAE suspension. DBAE mixed micelles exhibited a comparable anti-thrombolytic activity with a thrombosis inhibition rate of 63.18% compared with DBAE suspension in vivo. Thus, our study provides a promising drug delivery system to enhance the oral bioavailability and therapeutic efficacy of DBAE.

  14. Drug-conjugated PLA-PEG-PLA copolymers: a novel approach for controlled delivery of hydrophilic drugs by micelle formation.

    Science.gov (United States)

    Danafar, H; Rostamizadeh, K; Davaran, S; Hamidi, M

    2017-12-01

    A conjugate of the antihypertensive drug, lisinopril, with triblock poly(lactic acid)-poly(ethylene glycol)-poly(lactic acid) (PLA-PEG-PLA) copolymer was synthesized by the reaction of PLA-PEG-PLA copolymer with lisinopril in the presence of dicyclohexylcarbodiimide and dimethylaminopyridine. The conjugated copolymer was characterized in vitro by hydrogen nuclear magnetic resonance (HNMR), Fourier transform infrared (FTIR), differential scanning calorimetry (DSC) and gel permeation chromatography (GPC) techniques. Then, the lisinopril conjugated PLA-PEG-PLA were self-assembled into micelles in aqueous solution. The resulting micelles were characterized further by various techniques such as dynamic light scattering (DLS) and atomic force microscopy (AFM). The results revealed that the micelles formed by the lisinopril-conjugated PLA-PEG-PLA have spherical structure with the average size of 162 nm. The release behavior of conjugated copolymer, micelles and micelles physically loaded by lisinopril were compared in different media. In vitro release study showed that in contrast to physically loaded micelles, the release rate of micelles consisted of the conjugated copolymer was dependent on pH of media where it was higher at lower pH compared to the neutral medium. Another feature of the conjugated micelles was their more sustained release profile compared to the lisinopril-conjugated copolymer and physically loaded micelles.

  15. 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.

  16. Y-shaped Folic Acid-Conjugated PEG-PCL Copolymeric Micelles for Delivery of Curcumin.

    Science.gov (United States)

    Feng, Runliang; Zhu, Wenxia; Chu, Wei; Teng, Fangfang; Meng, Ning; Deng, Peizong; Song, Zhimei

    2017-01-01

    Curcumin is a natural hydrophobic product showing anticancer activity. Many studies show its potential use in the field of cancer treatment due to its safety and efficiency. However, its application is limited due to its low water-solubility and poor selective delivery to cancer. A Y-shaped folic acid-modified poly (ethylene glycol)-b-poly (ε-caprolactone)2 copolymer was prepared to improve curcumin solubility and realize its selective delivery to cancer. The copolymer was synthesized through selective acylation reaction of folic acid with α- monoamino poly(ethylene glycol)-b-poly(ε-caprolactone)2. Curcumin was encapsulated into the copolymeric micelles with 93.71% of encapsulation efficiency and 11.94 % of loading capacity. The results from confocal microscopy and cellular uptake tests showed that folic acid-modified copolymeric micelles could improve cellular uptake of curcumin in Hela and HepG2 cells compared with folic acid-unmodified micelles. In vitro cytotoxicity assay showed that folic acid-modified micelles improved anticancer activity against Hela and HepG2 cells in comparison to folic acidunmodified micelles. Meanwhile, both drug-loaded micelles demonstrated higher activity against Hela cell lines than HepG2. The research results suggested that the folic acid-modified Y-shaped copolymeric micelles should be used to enhance hydrophobic anticancer drugs' solubility and their specific delivery to folic acid receptors-overexpressed cancer. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  17. Tamoxifen-loaded polymeric micelles: preparation, physico-chemical characterization and in vitro evaluation studies.

    Science.gov (United States)

    Cavallaro, Gennara; Maniscalco, Laura; Licciardi, Mariano; Giammona, Gaetano

    2004-11-20

    Several samples of polymeric micelles, formed by amphiphilic derivatives of PHEA, obtained by grafting into polymeric backbone of PEGs and/or hexadecylamine groups (PHEA-PEG-C(16) and PHEA-C(16)) and containing different amount of Tamoxifen, were prepared. All Tamoxifen-loaded polymeric micelles showed to increase drug water solubility. TEM studies provided evidence of the formation of supramolecular core/shell architectures containing drug, in the nanoscopic range and with spherical shape. Samples with different amount of encapsulated Tamoxifen were subjected to in vitro cytotoxic studies in order to evaluate the effect of Tamoxifen micellization on cell growth inhibition. All samples of Tamoxifen-loaded polymeric micelles showed a significantly higher antiproliferative activity in comparison with free drug, probably attributable to fluidification of cellular membranes, caused by amphiphilic copolymers, that allows a higher penetration of the drug into tumoral cells. To gain preliminary information about the potential use of prepared micelles as Tamoxifen drug delivery systems, studies evaluating drug release ability of micelle systems in media mimicking biological fluids (buffer solutions at pH 7.4 and 5.5) and in human plasma were carried out. These studies, performed evaluating the amount of Tamoxifen that remains in solution as a function of time, showed that at pH 7.4, as well as in plasma, PHEA-C(16) polymeric micelles were able to release lower drug amounts than PHEA-PEG(5000)-C(16) ones, while at pH 5.5, the behavior difference between two kind of micelles was less pronounced.

  18. Light Scattering Study of Mixed Micelles Made from Elastin-Like Polypeptide Linear Chains and Trimers

    Science.gov (United States)

    Terrano, Daniel; Tsuper, Ilona; Maraschky, Adam; Holland, Nolan; Streletzky, Kiril

    Temperature sensitive nanoparticles were generated from a construct (H20F) of three chains of elastin-like polypeptides (ELP) linked to a negatively charged foldon domain. This ELP system was mixed at different ratios with linear chains of ELP (H40L) which lacks the foldon domain. The mixed system is soluble at room temperature and at a transition temperature (Tt) will form swollen micelles with the hydrophobic linear chains hidden inside. This system was studied using depolarized dynamic light scattering (DDLS) and static light scattering (SLS) to determine the size, shape, and internal structure of the mixed micelles. The mixed micelle in equal parts of H20F and H40L show a constant apparent hydrodynamic radius of 40-45 nm at the concentration window from 25:25 to 60:60 uM (1:1 ratio). At a fixed 50 uM concentration of the H20F, varying H40L concentration from 5 to 80 uM resulted in a linear growth in the hydrodynamic radius from about 11 to about 62 nm, along with a 1000-fold increase in VH signal. A possible simple model explaining the growth of the swollen micelles is considered. Lastly, the VH signal can indicate elongation in the geometry of the particle or could possibly be a result from anisotropic properties from the core of the micelle. SLS was used to study the molecular weight, and the radius of gyration of the micelle to help identify the structure and morphology of mixed micelles and the tangible cause of the VH signal.

  19. Nanoparticle packing within block copolymer micelles prepared by the interfacial instability method.

    Science.gov (United States)

    Nabar, Gauri M; Winter, Jessica O; Wyslouzil, Barbara E

    2018-05-02

    The interfacial instability method has emerged as a viable approach for encapsulating high concentrations of nanoparticles (NPs) within morphologically diverse micelles. In this method, transient interfacial instabilities at the surface of an emulsion droplet guide self-assembly of block co-polymers and NP encapsulants. Although used by many groups, there are no systematic investigations exploring the relationship between NP properties and micelle morphology. Here, the effect of quantum dot (QD) and superparamagnetic iron oxide NP (SPION) concentration on the shape, size, and surface deformation of initially spherical poly(styrene-b-ethylene oxide) (PS-b-PEO) micelles was examined. Multi-NP encapsulation and uniform dispersion within micelles was obtained even at low NP concentrations. Increasing NP concentration initially resulted in larger numbers of elongated micelles and cylinders with tightly-controlled diameters smaller than those of spherical micelles. Beyond a critical NP concentration, micelle formation was suppressed; the dominant morphology became densely-loaded NP structures that were coated with polymer and exhibited increased polydispersity. Transmission electron microscopy (TEM) and small angle X-ray scattering (SAXS) revealed that NPs in densely-loaded structures can be well-ordered, with packing volume fractions of up to 24%. These effects were enhanced in magnetic composites, possibly by dipole interactions. Mechanisms governing phase transitions triggered by NP loading in the interfacial instability process were proposed. The current study helps establish and elucidate the active role played by NPs in directing block copolymer assembly in the interfacial instability process, and provides important guiding principles for the use of this approach in generating NP-loaded block copolymer composites.

  20. Tailor-made dimensions of diblock copolymer truncated micelles on a solid by UV irradiation.

    Science.gov (United States)

    Liou, Jiun-You; Sun, Ya-Sen

    2015-09-28

    We investigated the structural evolution of truncated micelles in ultrathin films of polystyrene-block-poly(2-vinylpyridine), PS-b-P2VP, of monolayer thickness on bare silicon substrates (SiOx/Si) upon UV irradiation in air- (UVIA) and nitrogen-rich (UVIN) environments. The structural evolution of micelles upon UV irradiation was monitored using GISAXS measurements in situ, while the surface morphology was probed using atomic force microscopy ex situ and the chemical composition using X-ray photoelectron spectroscopy (XPS). This work provides clear evidence for the interpretation of the relationship between the structural evolution and photochemical reactions in PS-b-P2VP truncated micelles upon UVIA and UVIN. Under UVIA treatment, photolysis and cross-linking reactions coexisted within the micelles; photolysis occurred mainly at the top of the micelles, whereas cross-linking occurred preferentially at the bottom. The shape and size of UVIA-treated truncated micelles were controlled predominantly by oxidative photolysis reactions, which depended on the concentration gradient of free radicals and oxygen along the micelle height. Because of an interplay between photolysis and photo-crosslinking, the scattering length densities (SLD) of PS and P2VP remained constant. In contrast, UVIN treatments enhanced the contrast in SLD between the PS shell and the P2VP core as cross-linking dominated over photolysis in the presence of nitrogen. The enhancement of the SLD contrast was due to the various degrees of cross-linking under UVIN for the PS and P2VP blocks.

  1. Curcumin-Loaded Blood-Stable Polymeric Micelles for Enhancing Therapeutic Effect on Erythroleukemia.

    Science.gov (United States)

    Gong, Feirong; Chen, Dan; Teng, Xin; Ge, Junhua; Ning, Xianfeng; Shen, Ya-Ling; Li, Jian; Wang, Shanfeng

    2017-08-07

    Curcumin has high potential in suppressing many types of cancer and overcoming multidrug resistance in a multifaceted manner by targeting diverse molecular targets. However, the rather low systemic bioavailability resulted from its poor solubility in water and fast metabolism/excretion in vivo has hampered its applications in cancer therapy. To increase the aqueous solubility of curcumin while retaining the stability in blood circulation, here we report curcumin-loaded copolymer micelles with excellent in vitro and in vivo stability and antitumor efficacy. The two copolymers used for comparison were methoxy-poly(ethylene glycol)-block-poly(ε-caprolactone) (mPEG-PCL) and N-(tert-butoxycarbonyl)-l-phenylalanine end-capped mPEG-PCL (mPEG-PCL-Phe(Boc)). In vitro cytotoxicity evaluation against human pancreatic SW1990 cell line showed that the delivery of curcumin in mPEG-PCL-Phe(Boc) micelles to cancer cells was efficient and dosage-dependent. The pharmacokinetics in ICR mice indicated that intravenous (i.v.) administration of curcumin/mPEG-PCL-Phe(Boc) micelles could retain curcumin in plasma much better than curcumin/mPEG-PCL micelles. Biodistribution results in Sprague-Dawley rats also showed higher uptake and slower elimination of curcumin into liver, lung, kidney, and brain, and lower uptake into heart and spleen of mPEG-PCL-Phe(Boc) micelles, as compared with mPEG-PCL micelles. Further in vivo efficacy evaluation in multidrug-resistant human erythroleukemia K562/ADR xenograft model revealed that i.v. administration of curcumin-loaded mPEG-PCL-Phe(Boc) micelles significantly delayed tumor growth, which was attributed to the improved stability of curcumin in the bloodstream and increased systemic bioavailability. The mPEG-PCL-Phe(Boc) micellar system is promising in overcoming the key challenge of curcumin's to promote its applications in cancer therapy.

  2. Enhancing the specificity of polymerase chain reaction by graphene oxide through surface modification: zwitterionic polymer is superior to other polymers with different charges

    Science.gov (United States)

    Zhong, Yong; Huang, Lihong; Zhang, Zhisen; Xiong, Yunjing; Sun, Liping; Weng, Jian

    2016-01-01

    Graphene oxides (GOs) with different surface characteristics, such as size, reduction degree and charge, are prepared, and their effects on the specificity of polymerase chain reaction (PCR) are investigated. In this study, we demonstrate that GO with a large size and high reduction degree is superior to small and nonreduced GO in enhancing the specificity of PCR. Negatively charged polyacrylic acid (PAA), positively charged polyacrylamide (PAM), neutral polyethylene glycol (PEG) and zwitterionic polymer poly(sulfobetaine) (pSB) are used to modify GO. The PCR specificity-enhancing ability increases in the following order: GO-PAA Pfu DNA polymerase. Our data demonstrate that the size, reduction degree and surface charge of GO affect the specificity of PCR. Based on our results, zwitterionic polymer-modified GO may be used as an efficient additive for enhancing the specificity of PCR. PMID:27956830

  3. The crystal structure of zwitterionic 2-{[(4-iminiumyl-3-methyl-1,4-dihydropyridin-1-ylmethyl]carbamoyl}benzoate hemihydrate

    Directory of Open Access Journals (Sweden)

    C. S. Chidan Kumar

    2017-07-01

    Full Text Available The asymmetric unit of the title compound, C15H15N3O3·0.5H2O, comprises two 2-{[(4-iminiumyl-3-methyl-1,4-dihydropyridin-1-ylmethyl]carbamoyl}benzoate zwitterions (A and B and a water molecule. The dihedral angles between the pyridine and phenyl rings in the zwitterions are 53.69 (10 and 73.56 (11° in A and B, respectively. In the crystal, molecules are linked by N—H...O, O—H...O, C—H...O and C—H...π(ring hydrogen bonds into a three-dimensional network. The crystal structure also features π–π interactions involving the centroids of the pyridine and phenyl rings [centroid–centroid distances = 3.5618 (12 Å in A and 3.8182 (14 Å in B].

  4. Block Copolymer Micelles for Photonic Fluids and Crystals.

    Science.gov (United States)

    Poutanen, Mikko; Guidetti, Giulia; Gröschel, Tina I; Borisov, Oleg V; Vignolini, Silvia; Ikkala, Olli; Gröschel, Andre H

    2018-03-15

    Block copolymer micelles (BCMs) are self-assembled nanoparticles in solution with a collapsed core and a brush-like stabilizing corona typically in the size range of tens of nanometers. Despite being widely studied in various fields of science and technology, their ability to form structural colors at visible wavelength has not received attention, mainly due to the stringent length requirements of photonic lattices. Here, we describe the precision assembly of BCMs with superstretched corona, yet with narrow size distribution to qualify as building blocks for tunable and reversible micellar photonic fluids (MPFs) and micellar photonic crystals (MPCs). The BCMs form free-flowing MPFs with an average interparticle distance of 150-300 nm as defined by electrosteric repulsion arising from the highly charged and stretched corona. Under quiescent conditions, millimeter-sized MPCs with classical FCC lattice grow within the photonic fluid-medium upon refinement of the positional order of the BCMs. We discuss the generic properties of MPCs with special emphasis on surprisingly narrow reflected wavelengths with full width at half-maximum (fwhm) as small as 1 nm. We expect this concept to open a generic and facile way for self-assembled tunable micellar photonic structures.

  5. Vaccine Adjuvant Incorporation Strategy Dictates Peptide Amphiphile Micelle Immunostimulatory Capacity.

    Science.gov (United States)

    Zhang, Rui; Kramer, Jake S; Smith, Josiah D; Allen, Brittany N; Leeper, Caitlin N; Li, Xiaolei; Morton, Logan D; Gallazzi, Fabio; Ulery, Bret D

    2018-06-01

    Current vaccine research has shifted from traditional vaccines (i.e., whole-killed or live-attenuated) to subunit vaccines (i.e., protein, peptide, or DNA) as the latter is much safer due to delivering only the bioactive components necessary to produce a desirable immune response. Unfortunately, subunit vaccines are very weak immunogens requiring delivery vehicles and the addition of immunostimulatory molecules termed adjuvants to convey protective immunity. An interesting type of delivery vehicle is peptide amphiphile micelles (PAMs), unique biomaterials where the vaccine is part of the nanomaterial itself. Due to the modularity of PAMs, they can be readily modified to deliver both vaccine antigens and adjuvants within a singular construct. Through the co-delivery of a model antigenic epitope (Ovalbumin 319-340 -OVA BT ) and a known molecular adjuvant (e.g., 2,3-dipalmitoyl-S-glyceryl cysteine-Pam 2 C), greater insight into the mechanisms by which PAMs can exert immunostimulatory effects was gained. It was found that specific combinations of antigen and adjuvant can significantly alter vaccine immunogenicity both in vitro and in vivo. These results inform fundamental design rules that can be leveraged to fabricate optimal PAM-based vaccine formulations for future disease-specific applications. Graphical Abstract.

  6. Phospholipase A2 activity-dependent and -independent fusogenic activity of Naja nigricollis CMS-9 on zwitterionic and anionic phospholipid vesicles.

    Science.gov (United States)

    Chiou, Yi-Ling; Chen, Ying-Jung; Lin, Shinne-Ren; Chang, Long-Sen

    2011-11-01

    CMS-9, a phospholipase A(2) (PLA(2)) from Naja nigricollis venom, induced the death of human breast cancer MCF-7 cells accompanied with the formation of cell clumps without clear boundaries between cells. Annexin V-FITC staining indicated that abundant phosphatidylserine appeared on the outer membrane of MCF-7 cell clumps, implying the possibility that CMS-9 may promote membrane fusion via anionic phospholipids. To validate this proposition, fusogenic activity of CMS-9 on vesicles composed of zwitterionic phospholipid alone or a combination of zwitterionic and anionic phospholipids was examined. Although CMS-9-induced fusion of zwitterionic phospholipid vesicles depended on PLA(2) activity, CMS-9-induced fusion of vesicles containing anionic phospholipids could occur without the involvement of PLA(2) activity. Membrane-damaging activity of CMS-9 was associated with its fusogenicity. Moreover, CMS-9 induced differently membrane leakage and membrane fusion of vesicles with different compositions. Membrane fluidity and binding capability with phospholipid vesicles were not related to the fusogenicity of CMS-9. However, membrane-bound conformation and mode of CMS-9 depended on phospholipid compositions. Collectively, our data suggest that PLA(2) activity-dependent and -independent fusogenicity of CMS-9 are closely related to its membrane-bound modes and targeted membrane compositions. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. Evaluation of an ODS column modified with zwitterionic/nonionic mixed surfactants and its application to direct injection determination of inorganic anions.

    Science.gov (United States)

    Hasegawa, Takuya; Umemura, Tomonari; Koide, Akira; Chiba, Koichi; Ueki, Yuji; Tsunoda, Kin-ichi; Haraguchi, Hiroki

    2005-08-01

    An octadecylsilica (ODS) column modified with zwitterionic/nonionic mixed surfactants was evaluated for the direct injection determination of inorganic anions in biological fluids by ion chromatography. A zwitterionic surfactant (sulfobetaine-type) and a nonionic surfactant (polyoxyethylene-type) were used for a stationary-phase modification. When aqueous electrolyte solutions with concentrations of sub-mM to several mM were used as a mobile phase, the zwitterionic surfactant coated on the ODS surface exhibited unique separation selectivity for ionic species, while the nonionic surfactant coated on the ODS might have formed a hydrophilic network over the ODS surface and restricted matrix proteins from adsorbing on the stationary phase. Consequently, the mixed surfactant-modified column system allowed an efficient ion chromatographic separation of inorganic anions as well as a size-exclusive removal of column-fouling proteins. This separation system was applied to the direct injection determination of UV-absorbing anions in human saliva. The detection limits for nitrite, nitrate, iodide and thiocyanate were 3.1, 2.7, 4.5 and 25 microM, respectively, with UV detection at 210 nm (injection volume; 20 microl), and their relative standard deviations for 5 replicate measurements of saliva samples spiked with 100 microM each of those anions were 1.4, 0.9, 2.2 and 5.5%, respectively.

  8. Zwitterionic sulfobetaine-grafted poly(vinylidene fluoride) membrane with highly effective blood compatibility via atmospheric plasma-induced surface copolymerization.

    Science.gov (United States)

    Chang, Yung; Chang, Wan-Ju; Shih, Yu-Ju; Wei, Ta-Chin; Hsiue, Ging-Ho

    2011-04-01

    Development of nonfouling membranes to prevent nonspecific protein adsorption and platelet adhesion is critical for many biomedical applications. It is always a challenge to control the surface graft copolymerization of a highly polar monomer from the highly hydrophobic surface of a fluoropolymer membrane. In this work, the blood compatibility of poly(vinylidene fluoride) (PVDF) membranes with surface-grafted electrically neutral zwitterionic poly(sulfobetaine methacrylate) (PSBMA), from atmospheric plasma-induced surface copolymerization, was studied. The effect of surface composition and graft morphology, electrical neutrality, hydrophilicity and hydration capability on blood compatibility of the membranes were determined. Blood compatibility of the zwitterionic PVDF membranes was systematically evaluated by plasma protein adsorption, platelet adhesion, plasma-clotting time, and blood cell hemolysis. It was found that the nonfouling nature and hydration capability of grafted PSBMA polymers can be effectively controlled by regulating the grafting coverage and charge balance of the PSBMA layer on the PVDF membrane surface. Even a slight charge bias in the grafted zwitterionic PSBMA layer can induce electrostatic interactions between proteins and the membrane surfaces, leading to surface protein adsorption, platelet activation, plasma clotting and blood cell hemolysis. Thus, the optimized PSBMA surface graft layer in overall charge neutrality has a high hydration capability and the best antifouling, anticoagulant, and antihemolytic activities when comes into contact with human blood. © 2011 American Chemical Society

  9. DEVELOPMENT OF SEPARATION SYSTEMS FOR POLYNUCLEAR AROMATIC HYDROCARBON ENVIRONMENTAL CONTAMINANTS USING MICELLAR ELECTROKINETIC CHROMATOGRAPHY WITH MOLECULAR MICELLES AND FREE ZONE ELECTROPHORESIS

    Science.gov (United States)

    Of four systems available from the literature, based on cyclodextrins, dioctylsulfosuccinate, bile salts, and molecular micelles consisting of oligomers of undecylenic acid, the most successful separation system in our hands is based on the molecular micelles, oligomers of sodiu...

  10. 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.

  11. Olmesartan medoxomil-loaded mixed micelles: Preparation, characterization and in-vitro evaluation

    Directory of Open Access Journals (Sweden)

    Mohamed A. El-Gendy

    2017-12-01

    Full Text Available Olmesartan medoxomil (OLM is highly lipophilic in nature (log p = 4.31 which attributes to its low aqueous solubility contributing to its low bioavailability 25.6%. OLM was loaded into mixed micelles carriers in a trial to enhance its solubility, thus improving its oral bioavailability. OLM-loaded mixed micelles were prepared, using a Pluronic® mixture of F127 and P123, adopting the thin-film hydration method. Three drug: Pluronic® mixture ratios (1:40, 1:50and 1: 60 and various F127: P123 ratios were prepared. OLM Loaded mixed micelles showed stability up to 12 h. The particle size of the systems varied from 364.00 nm (F3 to 13.73 nm (F18 with accepted Poly dispersity index (PDI values. The in-vitro release studies of OLM from mixed micelles versus drug aqueous suspension were assessed using the reverse dialysis technique in a USP Dissolution tester apparatus (type II. The highest RE% (43% was achieved with OLM-loaded mixed micelles (F8 when compared to (35% of drug suspension.

  12. Polymeric micelles for ocular drug delivery: From structural frameworks to recent preclinical studies.

    Science.gov (United States)

    Mandal, Abhirup; Bisht, Rohit; Rupenthal, Ilva D; Mitra, Ashim K

    2017-02-28

    Effective intraocular drug delivery poses a major challenge due to the presence of various elimination mechanisms and physiological barriers that result in low ocular bioavailability after topical application. Over the past decades, polymeric micelles have emerged as one of the most promising drug delivery platforms for the management of ocular diseases affecting the anterior (dry eye syndrome) and posterior (age-related macular degeneration, diabetic retinopathy and glaucoma) segments of the eye. Promising preclinical efficacy results from both in-vitro and in-vivo animal studies have led to their steady progression through clinical trials. The mucoadhesive nature of these polymeric micelles results in enhanced contact with the ocular surface while their small size allows better tissue penetration. Most importantly, being highly water soluble, these polymeric micelles generate clear aqueous solutions which allows easy application in the form of eye drops without any vision interference. Enhanced stability, larger cargo capacity, non-toxicity, ease of surface modification and controlled drug release are additional advantages with polymeric micelles. Finally, simple and cost effective fabrication techniques render their industrial acceptance relatively high. This review summarizes structural frameworks, methods of preparation, physicochemical properties, patented inventions and recent advances of these micelles as effective carriers for ocular drug delivery highlighting their performance in preclinical studies. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. PEG-lipid micelles as drug carriers: physiochemical attributes, formulation principles and biological implication.

    Science.gov (United States)

    Gill, Kanwaldeep K; Kaddoumi, Amal; Nazzal, Sami

    2015-04-01

    PEG-lipid micelles, primarily conjugates of polyethylene glycol (PEG) and distearyl phosphatidylethanolamine (DSPE) or PEG-DSPE, have emerged as promising drug-delivery carriers to address the shortcomings associated with new molecular entities with suboptimal biopharmaceutical attributes. The flexibility in PEG-DSPE design coupled with the simplicity of physical drug entrapment have distinguished PEG-lipid micelles as versatile and effective drug carriers for cancer therapy. They were shown to overcome several limitations of poorly soluble drugs such as non-specific biodistribution and targeting, lack of water solubility and poor oral bioavailability. Therefore, considerable efforts have been made to exploit the full potential of these delivery systems; to entrap poorly soluble drugs and target pathological sites both passively through the enhanced permeability and retention (EPR) effect and actively by linking the terminal PEG groups with targeting ligands, which were shown to increase delivery efficiency and tissue specificity. This article reviews the current state of PEG-lipid micelles as delivery carriers for poorly soluble drugs, their biological implications and recent developments in exploring their active targeting potential. In addition, this review sheds light on the physical properties of PEG-lipid micelles and their relevance to the inherent advantages and applications of PEG-lipid micelles for drug delivery.

  14. 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 (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.

  15. Investigation of a new thermosensitive block copolymer micelle: hydrolysis, disruption, and release.

    Science.gov (United States)

    Pelletier, Maxime; Babin, Jérôme; Tremblay, Luc; Zhao, Yue

    2008-11-04

    Thermosensitive polymer micelles are generally obtained with block copolymers in which one block exhibits a lower critical solution temperature in aqueous solution. We investigate a different design that is based on the use of one block bearing a thermally labile side group, whose hydrolysis upon heating shifts the hydrophilic-hydrophobic balance toward the destabilization of block copolymer micelles. Atom transfer radical polymerization was utilized to synthesize a series of diblock copolymers composed of hydrophilic poly(ethylene oxide) (PEO) and hydrophobic poly(2-tetrahydropyranyl methacrylate) (PTHPMA). We show that micelles of PEO-b-PTHPMA in aqueous solution can be destabilized as a result of the thermosensitive hydrolytic cleavage of tetrahydropyranyl (THP) groups that transforms PTHPMA into hydrophilic poly(methacrylic acid). The three related processes occurring in aqueous solution, namely, hydrolytic cleavage of THP, destabilization of micelles, and release of loaded Nile Red (NR), were investigated simultaneously using 1H NMR, dynamic light scattering, and fluorescence spectroscopy, respectively. At 80 degrees C, the results suggest that the three events proceed with a similar kinetics. Although slower than at elevated temperatures, the disruption of PEO-b-PTHPMA micelles can take place at the body temperature (approximately 37 degrees C), and the release kinetics of NR can be adjusted by changing the relative lengths of the two blocks or the pH of the solution.

  16. 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 A B 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.

  17. Solubilization of poorly soluble photosensitizer hypericin by polymeric micelles and polyethylene glycol.

    Science.gov (United States)

    Búzová, Diana; Kasák, Peter; Miškovský, Pavol; Jancura, Daniel

    2013-06-01

    Hypericin (Hyp) is a promising photosensitizer for photodiagnostic and photodynamic therapy of cancer. However, Hyp has a large conjugated system and in aqueous solutions forms insoluble aggregates which do not possess biological activity. This makes intravenous injection of Hyp problematic and restricts its medical applications. To overcome this problem, Hyp is incorporated into drug delivery systems which can increase its solubility and bioavailability. One of the possibilities is utilization of polymeric micelles. The most used hydrophilic block for preparation of polymeric micelles is polyethylen glycol (PEG). PEG is a polymer which for its lack of immunogenicity, antigenicity and toxicity obtained approval for use in human medicine. In this work we have studied the solubilization of Hyp aggregates in the presence of PEG-PE and PEG-cholesterol micelles. The concentration of polymeric micelles which allows total monomerization of Hyp corresponds to the critical micellar concentration of these micelles (~10(-6) M). We have also investigated the effect of the molecular weight and concentration of PEG on the transition of aggregated Hyp to its monomeric form. PEGs with low molecular weight ( 2000 g/mol efficiently transform Hyp aggregates to the monomeric state of this photosensitizer.

  18. Antiproliferative activity of tea catechins associated with casein micelles, using HT29 colon cancer cells.

    Science.gov (United States)

    Haratifar, S; Meckling, K A; Corredig, M

    2014-02-01

    Numerous studies have shown that green tea polyphenols display anticancer activities in many organ sites by using different experimental models in rodents and in cultured cell lines in vitro. The present study tested the ability of casein micelles to deliver biologically active concentrations of polyphenols to HT-29 colon cancer cells. Epigallocatechin gallate (EGCG), the major catechin found in green tea, was used as the model molecule, as it has been shown to have antiproliferative activity on colon cancer cells. In the present work, we hypothesized that due to the binding of caseins with EGCG, casein micelles may be an ideal platform for the delivery of this bioactive molecule and that the binding would not affect the bioaccessibility of EGCG. The cytotoxicity and proliferation behavior of HT-29 colon cancer cells when exposed to free EGCG was compared with that of nanoencapsulated EGCG in casein micelles of skim milk. Epigallocatechin gallate-casein complexes were able to decrease the proliferation of HT-29 cancer cells, demonstrating that bioavailability may not be reduced by the nanoencapsulation. As casein micelles may act as protective carriers for EGCG in foods, it was concluded that nanoencapsulation of tea catechins in casein micelles may not diminish their antiproliferative activity on colon cancer cells compared with free tea catechins. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  19. Selective in vitro anticancer effect of superparamagnetic iron oxide nanoparticles loaded in hyaluronan polymeric micelles.

    Science.gov (United States)

    Smejkalová, Daniela; Nešporová, Kristina; Huerta-Angeles, Gloria; Syrovátka, Jakub; Jirák, Daniel; Gálisová, Andrea; Velebný, Vladimír

    2014-11-10

    Due to its native origin, excellent biocompatibility and biodegradability, hyaluronan (HA) represents an attractive polymer for superparamagnetic iron oxide nanoparticles (SPION) coating. Herein, we report HA polymeric micelles encapsulating oleic acid coated SPIONs, having a hydrodynamic size of about 100 nm and SPION loading capacity of 1-2 wt %. The HA-SPION polymeric micelles were found to be selectively cytotoxic toward a number of human cancer cell lines, mainly those of colon adenocarcinoma (HT-29). The selective inhibition of cell growth was even observed when the SPION loaded HA polymeric micelles were incubated with a mixture of control and cancer cells. The selective in vitro inhibition could not be connected with an enhanced CD44 uptake or radical oxygen species formation and was rather connected with a different way of SPION intracellular release. While aggregated iron particles were visualized in control cells, nonaggregated solubilized iron oxide particles were detected in cancer cells. In vivo SPION accumulation in intramuscular tumor following an intravenous micelle administration was confirmed by magnetic resonance (MR) imaging and histological analysis. Having a suitable hydrodynamic size, high magnetic relaxivity, and being cancer specific and able to accumulate in vivo in tumors, SPION-loaded HA micelles represent a promising platform for theranostic applications.

  20. 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.

  1. Fisetin and polymeric micelles encapsulating fisetin exhibit potent cytotoxic effects towards ovarian cancer cells.

    Science.gov (United States)

    Xiao, Xue; Zou, Juan; Fang, Yin; Meng, Yibo; Xiao, Chao; Fu, Jiaxin; Liu, Shiyu; Bai, Peng; Yao, Yuan

    2018-03-15

    The anti-tumor activities of Natural compounds and their derivatives are of great interest to pharmaceutical industries. Fisetin is one of prospective natural compounds in this regard but unfortunately with poor hydrophilicity. The effects of unmodified and modified fisetin in cultured ovarian cancer cells were compared by transmission electronmicroscopy to determine apoptotic bodies, MTT assay to quantitate cell numbers, and fluorescence activated cell sorting analyse of various markers to determine the apoptotic state. In addition, the efficacy of fisetin and fisetin-micelles in vivo was determined by using immunocompromised mice. Apoptosis was measured by established markers using both western blot analysis and immunochemistry. Angiogenesis in a xenograft mouse model carring SKOV3 cells was evaluated by color Doppler ultrasound and immunohistochemistry. Multiple lines of evidence indicated that fisetin and fisetin micelles induce apoptosis in ovarian cancer cells in a dose-dependent manner. Histological analysis, terminal deoxynucleotidyltransferase-mediated nick-end labeling assay, western blot, immunohistochemical detection and microvessel density detection demonstrated that fisetin and fisetin micelles induced increased tumor apoptosis, proliferation suppression and antiangiogenesis activities. As far as we know, the present study is the first time to demonstrate the potency of both fisetin and fisetin micelles inducing apoptosis in ovarian cancer cells. Further studies will be needed to validate the therapeutic potential of fisetin and fisetin micelles in ovarian cancer treatment.

  2. Freezing polystyrene-b-poly(2-vinylpyridine) micelle nanoparticles with different nanostructures and sizes.

    Science.gov (United States)

    Fan, Hailong; Jin, Zhaoxia

    2014-04-28

    Herein we report how to control the nanostructures and sizes of polystyrene-b-poly(2-vinylpyridine) (PS-b-P2VP) nanoparticles via manipulating freezing in solvent-exchange. By characterizing and analyzing the distinct structural features of the obtained nanoparticles, we recognized that micelle self-assembly happens in the precipitation of PS-b-P2VP when water is added into the block copolymer (BCP) solution. Solvent properties significantly influence micelle types that are vesicles in acetone/H2O and spherical micelles in tetrahydrofuran/H2O, respectively, thus further inducing different frozen nanostructures of the obtained nanoparticles, onion-like in acetone/H2O and large compound micelles in tetrahydrofuran/H2O. By changing the concentration of the block copolymers and the Vsolvent/VH2O ratio to modify the freezing stage at which block copolymer micelles are frozen, we can further control the size of the nanoparticles. Moreover, small molecules (phosphotungstic acid, pyrene, 1-pyrenebutyric acid) can be trapped into the block copolymer nanoparticles via the freezing process. Their distribution in the nanoparticles relies not only on the solvent property, but also on their interactions with block copolymers. The hybrid nanoparticles with ordered distribution of small molecules can be further changed to partially-void nanoparticles. Our study demonstrated that manipulating the freezing of block copolymers in the solvent exchange process is a simple and controllable fabrication method to generate BCP nanoparticles with different architectures.

  3. Spontaneous Evolution of Nanostructure in Composite Films Consisting of Mixtures of Two Different Block Copolymer Micelles

    Science.gov (United States)

    Kim, Sehee; Char, Kookheon; Sohn, Byeong-Hyeok

    2010-03-01

    Diblock copolymers consisting of two immiscible polymer blocks covalently bonded together form various self-assembled nanostructures such as spheres, cylinders, and lamellae in bulk phase. In a selective solvent, however, they assemble into micelles with soluble corona brushes and immiscible cores. Both polystyrene-poly(4-vinylpyridine) (PS-b-P4VP) and polystyrene-poly(2-vinylpyridine) (PS-b-P2VP) diblock copolymers form micelles with PS coronas and P4VP or P2VP cores in a PS selective solvent (toluene). By varying the mixture ratio between PS-b-P4VP and PS-b-P2VP, composite films based on the micellar mixtures of PS-b-P4VP and PS-b-P2VP were obtained by spin-coating, followed by the solvent annealing with tetrahydrofuran (THF) vapor. Since THF is a solvent for both PS and P2VP blocks and, at the same time, a non-solvent for the P4VP block, PS-P2VP micelles transformed to lamellar multilayers while PS-P4VP micelles remained intact during the THF annealing. The spontaneous evolution of nanostructure in composite films consisting of lamellae layers with BCP micelles were investigated in detail by cross-sectional TEM and AFM.

  4. Solubilization of trace organics in block copolymer micelles for environmental separation using membrane extraction principles

    Energy Technology Data Exchange (ETDEWEB)

    Hatton, T.A.

    1992-12-01

    The solubilization of a range of polycyclic aromatic hydrocarbons in block copolymer micelles has been studied as a function of polymer composition, architecture, and temperature. Micelle formation is favored at high temperatures, leading to significant enhancements in solubilization capacity. At low temperatures, however, micelles do not form and the solubilization capacity of the block copolymer solution for the organics is low; this provides a convenient method for the regeneration of micellar solutions used as solvents'' in the treatment of contaminated feed streams using membrane extraction principles. It has also been shown (in collaboration with K.P. Johnston of University of Texas, Austin) that supercritical CO[sub 2] can be used effectively for micelle regeneration. Theoretical calculations of the structure of block copolymer micelles in the presence and absence of solutes using self-consistent mean-field lattice theories have successfully captured the trends observed with changing polymer composition and architecture, often quantitatively. The temperature and composition dependence of the micellar properties were determined by allowing the individual polymer segments to assume both polar and non-polar conformations.

  5. 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.

  6. Temperature Effect on Micelle Formation: Molecular Thermodynamic Model Revisited.

    Science.gov (United States)

    Khoshnood, Atefeh; Lukanov, Boris; Firoozabadi, Abbas

    2016-03-08

    Temperature affects the aggregation of macromolecules such as surfactants, polymers, and proteins in aqueous solutions. The effect on the critical micelle concentration (CMC) is often nonmonotonic. In this work, the effect of temperature on the micellization of ionic and nonionic surfactants in aqueous solutions is studied using a molecular thermodynamic model. Previous studies based on this technique have predicted monotonic behavior for ionic surfactants. Our investigation shows that the choice of tail transfer energy to describe the hydrophobic effect between the surfactant tails and the polar solvent molecules plays a key role in the predicted CMC. We modify the tail transfer energy by taking into account the effect of the surfactant head on the neighboring methylene group. The modification improves the description of the CMC and the predicted micellar size for aqueous solutions of sodium n-alkyl sulfate, dodecyl trimethylammonium bromide (DTAB), and n-alkyl polyoxyethylene. The new tail transfer energy describes the nonmonotonic behavior of CMC versus temperature. In the DTAB-water system, we redefine the head size by including the methylene group, next to the nitrogen, in the head. The change in the head size along with our modified tail transfer energy improves the CMC and aggregation size prediction significantly. Tail transfer is a dominant energy contribution in micellar and microemulsion systems. It also promotes the adsorption of surfactants at fluid-fluid interfaces and affects the formation of adsorbed layer at fluid-solid interfaces. Our proposed modifications have direct applications in the thermodynamic modeling of the effect of temperature on molecular aggregation, both in the bulk and at the interfaces.

  7. 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.

  8. 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

    A micelle based nanosensor was synthesized and investigated as a ratiometric pH sensor for use in measurements in living cells by fluorescent microscopy. The nanosensor synthesis was based on self-assembly of an amphiphilic triblock copolymer, which was chemically cross-linked after micelle......-linked by an amidation reaction using 3,6,9-trioxaundecandioic acid cross-linker. The cross-linked micelle was functionalized with two pH sensitive fluorophores and one reference fluorophore, which resulted in a highly uniform ratiometric pH nanosensor with a diameter of 29 nm. The use of two sensor fluorophores...... provided a sensor with a very broad measurement range that seems to be influenced by the chemical design of the sensor. Cell experiments show that the sensor is capable of monitoring the pH distributions in HeLa cells....

  9. Reduction-Triggered Transformation of Crosslinking Modules of Disulfide-Containing Micelles with Chemically Tunable Rates.

    Science.gov (United States)

    Deng, Zhengyu; Yuan, Shuai; Xu, Ronald X; Liang, Haojun; Liu, Shiyong

    2018-05-16

    A dilemma exists between the circulation stability and cargo release/mass diffusion at desired sites for designing delivery nanocarriers and in vivo nanoreactors. We herein report disulfide-crosslinked (DCL) micelles exhibiting reduction-triggered switching of crosslinking modules and synchronized hydrophobic-to-hydrophilic transition. Tumor cell-targeted DCL micelles undergo cytoplasmic milieu-triggered disulfide cleavage and cascade self-immolative decaging reactions at chemically adjustable rates, generating primary amine moieties. Extensive amidation reactions with neighboring ester moieties then occur due to high local concentrations and suppression of apparent amine pKa within hydrophobic cores, leading to the transformation of crosslinking modules and formation of tracelessly crosslinked (TCL) micelles with hydrophilic cores inside live cells. We further integrate this design principle with theranostic nanocarriers for selective intracellular drug transport guided by enhanced magnetic resonance (MR) imaging performance. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Molecular dynamics simulations of helical antimicrobial peptides in SDS micelles: what do point mutations achieve?

    DEFF Research Database (Denmark)

    Khandelia, Himanshu; Kaznessis, Yiannis N

    2005-01-01

    We report long time scale simulations of the 18-residue helical antimicrobial peptide ovispirin-1 and its analogs novispirin-G10 and novispirin-T7 in SDS micelles. The SDS micelle serves as an economical and effective model for a cellular membrane. Ovispirin, which is initially placed along...... a micelle diameter, diffuses out to the water-SDS interface and stabilizes to an interface-bound steady state in 16.35 ns of simulation. The final conformation, orientation, and the structure of ovispirin are in good agreement with the experimentally observed properties of the peptide in presence of lipid...... bilayers. The simulation succeeds in capturing subtle differences of the membrane-bound peptide structure as predicted by solid state NMR. The novispirins also undergo identical diffusion patterns and similar final conformations. Although the final interface-bound states are similar, the simulations...

  11. Characterization of lipase in reversed micelles formulated by Cibacron Blue F-3GA modified Span 85

    DEFF Research Database (Denmark)

    Zhang, Dong Hao; Guo, Zheng; Sun, Yan

    2007-01-01

    Sorbitan trioleate (Span 85) modified by Cibacron Blue F-3GA (CB) was prepared and used as an affinity surfactant to formulate a reversed micellar system for Candida rugosa lipase (CRL) solubilization. The system was characterized and evaluated by employing CRL-catalyzed hydrolysis of olive oil...... of the encapsulated lipase remained unchanged, but the apparent activity was significantly higher than that of the native enzyme in bulk solution. Kinetic studies indicated that the encapsulated lipase in the reversed micelles of CB-formulated Span 85 followed the Michaelis-Menten equation. The Michaelis constant...... was found to decrease with increasing surfactant concentration, suggesting an increase of the enzyme affinity for the substrate. Stability of the lipase in the reversed micelles was negatively correlated to W0. Introduction Reversed micelles are nanometer-scale transparent aggregates of water and surfactant...

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

    Directory of Open Access Journals (Sweden)

    Takahiro Sato

    2018-01-01

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

  13. The α-chymotrypsin and its hydrophobic derivatives in inverse micelles

    International Nuclear Information System (INIS)

    Pitre, Franck

    1993-01-01

    The α-chymotrypsin is among the most used enzymes, notably and particularly in medicine for therapeutic treatments as well as in biochemistry to determine the amine acid sequence of proteins. This research thesis addresses the study of interactions between a micro-emulsion system and an enzymatic system, and more particularly the behaviour of α-chymotrypsin in AOT inverse micelles. After a brief description of the inverse micellar system and of previously obtained results on the solubilisation of α-chymotrypsin in inverse micelles, the author reports the study of the inverse micellar phase in presence of α-chymotrypsin at the vicinity of the maximum solubility. Various techniques are used for this purpose: UV-visible absorption spectrophotometry, conductometry, and X ray scattering. Then, the author describes the chemical modification of α-chymotrypsin, and reports the study of structural as well as reaction modifications introduced during the solubilisation of α-chymotrypsin modified in inverse micelles [fr

  14. Study of the interaction of potassium ion channel protein with micelle by molecular dynamics simulation

    Science.gov (United States)

    Shantappa, Anil; Talukdar, Keka

    2018-04-01

    Ion channels are proteins forming pore inside the body of all living organisms. This potassium ion channel known as KcsA channel and it is found in the each cell and nervous system. Flow of various ions is regulated by the function of the ion channels. The nerve ion channel protein with protein data bank entry 1BL8, which is basically an ion channel protein in Streptomyces Lividans and which is taken up to form micelle-protein system and the system is analyzed by using molecular dynamics simulation. Firstly, ion channel pore is engineered by CHARMM potential and then Micelle-protein system is subjected to molecular dynamics simulation. For some specific micelle concentration, the protein unfolding is observed.

  15. Phase behavior of casein micelles/exocellular polysaccharide mixtures: Experiment and theory

    Science.gov (United States)

    Tuinier, R.; de Kruif, C. G.

    1999-05-01

    Dispersions of casein micelles and an exocellular polysaccharide (EPS), obtained from Lactococcus lactis subsp. cremoris NIZO B40 EPS, show a phase separation. The phase separation is of the colloidal gas-liquid type. We have determined a phase diagram that describes the separation of skim milk with EPS into a casein-micelle rich phase and an EPS rich phase. We compare the phase diagram with those calculated from theories developed by Vrij, and by Lekkerkerker and co-workers, showing that the experimental phase boundary can be predicted quite well. From dynamic light scattering measurements of the self-diffusion of the casein micelles in the presence of EPS the spinodal could be located and it corresponds with the experimental phase boundary.

  16. 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.

  17. 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 

  18. 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

  19. mPEG-PLA Micelle for Delivery of Effective Parts of Andrographis Paniculata.

    Science.gov (United States)

    Yao, Hailu; Song, Shiyong; Miao, Xiaolu; Liu, Xiao; Zhao, Junli; Wang, Zhen; Shao, Xiaoting; Zhang, Yu; Han, Guang

    2018-01-01

    Many studies have shown that Andrographis paniculata (Burm. f.) Nees has a good anti-tumor effect, but poor solubility in water and poor bioavailability hinder the modernization of it. To formulate the effective parts (mainly diterpene lactones) of Andrographis paniculata (AEP) into targeting drug delivery system, a series of poly(ethylene glycol)-poly(D.L-lactic acid)(mPEG-PLA) with different ratio of hydrophilic and hydrophobic segment was synthetized to encapsulate AEP. AEP micelles were prepared by a simple solvent-evaporation method. According to the loading capacity, the best polymer was chosen. mPEG-PLA micelles were characterized in terms of drug entrapping efficiency, loading capacity, size, the crystalline state of AEP, stability and release profile. Meanwhile, the cytotoxicity of micelles on mouse breast cancer 4T-1 was investigated. These micelle (mPEG-PLA-AEP) particles had a size of (92.84±5.63) nm and a high entrapping efficiency and loading capacity of (91.00±11.53)% and (32.14±3.02)%(w/w), respectively. The powder DSC showed that drugs were well encapsulated in the core of micelles. mPEG-PLA-AEP had a good stability against salt dissociation, protein adsorption and anion substitution and the solubility of andrographolide (AG) and 14-deoxy-11,12-didehydroandrographolide(DDAG) in AEP increased 4.51 times and 2.12 times in water, and the solubility of DAG showed no difference. mPEG-PLA-AEP had the same release profile in different dissolution medium. Cytotoxicity testing in vitro demonstrated that mPEG-PLA-AEP exhibited higher cell viability inhibition in mouse breast cancer 4T-1 than free AEP. mPEG-PLA micelles offer a promising alternative for TCM therapy with higher solubility and improved antitumor effect. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  20. Surface Design in Solid-State Dye Sensitized Solar Cells: Effects of Zwitterionic Co-adsorbents on Photovoltaic Performance

    KAUST Repository

    Wang, Mingkui

    2009-07-10

    In solid-state dye sensitized solar cells (SSDSCs) charge recombination at the dye-hole transporting material interface plays a critical role in the cell efficiency. For the first time we report on the influence of dipolar coadsorbents on the photovoltaic performance of sensitized hetero-junction solar cells. In the present study, we investigated the effect of two zwitterionic butyric acid derivatives differing only in the polar moiety attached to their common 4 carbon-chain acid, i.e., 4-guanidinobutyric acid (GBA) and 4-aminobutyric acid (ABA). These two molecules were implemented as coadsorbents in conjunction with Z907Na dye on the SSDSC. It was found that a Z907Na/GBA dye/co-adsorbent combination increases both the open circuit voltage (V oc) and short-circuit current density ( Jsc) as compared to using Z907Na dye alone. The Z907Na/ABA dye/co-adsorbent combination increases the Jsc. Impedance and transient photovoltage investigations elucidate the cause of these remarkable observations. ©2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Effect of static mixer on the performance of compact plate heat exchanger with zwitterionic type of drag-reducing additives

    Energy Technology Data Exchange (ETDEWEB)

    Blais, C.; Wollerstrand, J.

    1997-06-01

    The main task of the project was to investigate the influence of drag-reducing additives (DRA) dissolved in circulating hot water on heat transfer in compact plate heat exchangers (PHE). Furthermore the result of flow disturbance (static mixing) immediately before the PHE on pressure drop and heat transfer was clarified. The project used a new type of DRA (surfactants of zwitterionic type) for two different temperature ranges. A dedicated test rig, `Ansgar`, was built for the purpose. Good thermal and mechanical stability also outside the operating range was observed except some sensitivity for water hardness at high temperatures for DRA2. Similarly to known investigations, the heat transfer coefficient was significantly reduced by DRA in heat exchangers. In PHE used however, the heat transfer reduction was considerably lower in the high flow region. A static mixer placed in front of the PHE was found to significantly improve heat transfer, especially at high flow rates. On the other hand, an additional pressure drop was introduced. Therefore the optimal choice of static mixer needs further investigation. Specially designed PHE combining mixing and heat transfer functions could be beneficial to reducing the effects of additives in thermal systems. The relaxation time (RT) of drag-reducing additives in water solutions flowing through test pipes with known geometries was estimated by monitoring specific pressure drop variation along the pipe. These preliminary experiments in respect to relaxation time showed that RT depends on the flow rate and on the temperature 12 refs, 11 figs, 1 tab

  2. Crystal structure of a 2:1 piroxicam–gentisic acid co-crystal featuring neutral and zwitterionic piroxicam molecules

    Energy Technology Data Exchange (ETDEWEB)

    Horstman, Elizabeth M.; Bertke, Jeffery A.; Woods, Toby J.; Kenis, Paul J. A.

    2016-11-04

    A new 2:1 co-crystal of piroxicam and gentisic acid [systematic name: 4-hydroxy-1,1-dioxo-N-(pyridin-2-yl)-2H-1λ6,2-benzothiazine-3-carboxamide–2-(4-oxido-1,1-dioxo-2H-1λ6,2-benzothiazine-3-amido)pyridin-1-ium–2,5-dihydroxybenzoic acid, 2C15H13N3O4S·C7H6O4] has been synthesized using a microfluidic platform and initially identified using Raman spectroscopy. In the co-crystal, one piroxicam molecule is in its neutral form and an intramolecular O—H...O hydrogen bond is observed. The other piroxicam molecule is zwitterionic (proton transfer from the OH group to the pyridine N atom) and two intramolecular N—H...O hydrogen bonds occur. The gentisic acid molecule shows whole-molecule disorder over two sets of sites in a 0.809(2):0.191(2) ratio. In the crystal, extensive hydrogen bonding between the components forms layers propagating in theabplane.

  3. Crystal structure of a 2:1 piroxicam–gentisic acid co-crystal featuring neutral and zwitterionic piroxicam molecules

    Directory of Open Access Journals (Sweden)

    Elizabeth M. Horstman

    2016-12-01

    Full Text Available A new 2:1 co-crystal of piroxicam and gentisic acid [systematic name: 4-hydroxy-1,1-dioxo-N-(pyridin-2-yl-2H-1λ6,2-benzothiazine-3-carboxamide–2-(4-oxido-1,1-dioxo-2H-1λ6,2-benzothiazine-3-amidopyridin-1-ium–2,5-dihydroxybenzoic acid, 2C15H13N3O4S·C7H6O4] has been synthesized using a microfluidic platform and initially identified using Raman spectroscopy. In the co-crystal, one piroxicam molecule is in its neutral form and an intramolecular O—H...O hydrogen bond is observed. The other piroxicam molecule is zwitterionic (proton transfer from the OH group to the pyridine N atom and two intramolecular N—H...O hydrogen bonds occur. The gentisic acid molecule shows whole-molecule disorder over two sets of sites in a 0.809 (2:0.191 (2 ratio. In the crystal, extensive hydrogen bonding between the components forms layers propagating in the ab plane.

  4. Molecular fouling resistance of zwitterionic and amphiphilic initiated chemically vapor-deposited (iCVD) thin films

    Energy Technology Data Exchange (ETDEWEB)

    Yang, R; Goktekin, E; Wang, MH; Gleason, KK

    2014-08-08

    Biofouling is a universal problem in various applications ranging from water purification to implantable biomedical devices. Recent advances in surface modification have created a rich library of antifouling surface chemistries, many of which can be categorized into one of the two groups: hydrophilic surfaces or amphiphilic surfaces. We report the straightforward preparation of antifouling thin film coatings in both categories via initiated chemical vapor deposition. A molecular force spectroscopy-based method is demonstrated as a rapid and quantitative assessment tool for comparing the differences in antifouling characteristics. The fouling propensity of single molecules, as opposed to bulk protein solution or bacterial culture, is assessed. This method allows for the interrogation of molecular interaction without the complication resulted from protein conformational change or micro-organism group interactions. The molecular interaction follows the same trend as bacterial adhesion results obtained previously, demonstrating that molecular force probe is a valid method for the quantification and mechanistic examination of fouling. In addition, the molecular force spectroscopy-based method is able to distinguish differences in antifouling capability that is not resolvable by traditional static protein adsorption tests. To lend further insight into the intrinsic fouling resistance of zwitterionic and amphiphilic surface chemistries, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, advancing and receding water contact angles, and atomic force microscopy are used to elucidate the film properties that are relevant to their antifouling capabilities.

  5. Integrated antibacterial and antifouling surfaces via cross-linking chitosan-g-eugenol/zwitterionic copolymer on electrospun membranes.

    Science.gov (United States)

    Li, Zhenguang; Hu, Wenhong; Zhao, Yunhui; Ren, Lixia; Yuan, Xiaoyan

    2018-04-27

    Integrated antibacterial and antifouling surfaces in favor of avoiding implant-related infections are necessarily required for biomaterials when they contact with the body fluid. In this work, an antibacterial and antifouling membrane was developed via cross-linking chitosan-g-eugenol and the zwitterionic copolymer poly(sulfobetaine methylacrylate-co-2-aminoethyl methacrylate) on the electrospun polycarbonate urethane substrate using genipin as a cross-linker. Antibacterial assays demonstrated that the prepared membranes had efficient antibacterial activity with 92.8 ± 2.5% and 95.2 ± 1.3% growth inhibition rates against Escherichia coli and Staphylococcus aureus, respectively. The investigations on antifouling activity and hemocompatibility of the membranes showed significant resistances to bacterial attachment, non-specific protein adsorption and platelet adhesion, and presented lower hemolytic activity and good anticoagulant activity as well. Moreover, cell culture assays indicated that the prepared membranes exerted no obvious cytotoxicity with more than 80% of relative L929 fibroblast viability. Therefore, the membranes with integrated antibacterial and antifouling properties could be potentially applied in promising indwelling devices. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. Molecular and Thermodynamic Properties of Zwitterions versus Ionic Liquids: A Comprehensive Computational Analysis to Develop Advanced Separation Processes.

    Science.gov (United States)

    Moreno, Daniel; Gonzalez-Miquel, Maria; Ferro, Victor R; Palomar, Jose

    2018-04-05

    Zwitterion ionic liquids (ZIs) are compounds in which both counterions are covalently tethered, conferring them with unique characteristics; however, most of their properties are still unknown, representing a bottleneck to exploit their practical applications. Herein, the molecular and fluid properties of ZIs and their mixtures were explored by means of quantum chemical analysis based on the density functional theory (DFT) and COSMO-RS method, and compared against homologous ionic liquids (ILs) to provide a comprehensive overview of the effect of the distinct structures on their physicochemical and thermodynamic behavior. Overall, ZIs were revealed as compounds with higher polarity and stronger hydrogen-bonding capacity, implying higher density, viscosity, melting point, and even lower volatility than structurally similar ILs. The phase equilibrium of binary and ternary systems supports stronger attractive interactions between ZIs and polar compounds, whereas higher liquid-liquid immiscibility with nonpolar compounds may be expected. Ultimately, the performance of ZIs in the wider context of separation processes is illustrated, while providing molecular insights to allow their selection and design for relevant applications. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Structural diversity of three Cu(II) compounds based on a new tripodal zwitterionic ligand: Syntheses, structures and properties

    Science.gov (United States)

    Zhou, Jie; Zhao, Jing-Song; Feng, Jing; Zhang, Xiao-Feng; Xu, Jian; Du, Lin; Xie, Ming-Jin; Zhao, Qi-Hua

    2018-03-01

    An exploration of reactions of 1,1‧,1″-(benzene-1,3,5-triyltris(methylene))tris(4-carboxypyridinium)-tribromide (H3LBr3) with Cu(II) salt under different pH conditions has led to the formation of three complexes, [Cu(HL)2(H2O)3]·4(ClO4)·3H2O (1), [Cu2(HL)(μ3-OH)(μ2-H2O)(H2O)2]·4(ClO4)·6H2O (2), and [Cu3(L)2Cl6(H2O)4]·4H2O (3). Single-crystal X-ray analyses revealed that complex 1 displays a discrete mononuclear structure with the ligand in a bowl-shaped configuration. Complex 2 possesses a tetranuclear 1D beaded chain structure. While complex 3 features a discrete trinuclear 'H-type' structure with the ligand in a chair-like configuration. The distinct compositions and structures of 1-3 are mainly ascribed to the different pH values of the reaction solution, the influences of anions, as well as the configurations which the zwitterion ligands adopt. The magnetic properties of 2, and the photoluminescence properties of 2, and 3 have been investigated. Moreover, powder X-ray diffraction, infrared spectroscopy, and elemental analysis were also performed.

  8. Methacrylic Zwitterionic, Thermoresponsive, and Hydrophilic (Co)Polymers via Cu(0)-Polymerization: The Importance of Halide Salt Additives.

    Science.gov (United States)

    Simula, Alexandre; Anastasaki, Athina; Haddleton, David M

    2016-02-01

    The synthesis of hydrophilic, thermoresponsive, and zwitterionic polymethacrylates is reported by Cu(0)-mediated reversible deactivation radical polymerization in water and/or water/alcohol mixtures. The predisproportionation of [Cu(I) (PMDETA)Cl] in water prior to initiator and monomer addition is exploited to yield well-defined polymethacrylates with full monomer conversions in 30 min. The addition of supplementary halide salts (NaCl) enables the synthesis of various molecular weight poly[poly(ethylene glycol) methyl ether methacrylate] (PEGMA475) (DPn = 10-80, Mn ≈ 10,000-40 000 g mol(-1)) with full monomer conversion and narrow molecular weight distributions attained in all cases (Đ ≈ 1.20-1.30). A bifunctional PEG initiator (average Mn ≈ 1000 g mol(-1)) is utilized for the polymerization of a wide range of methacrylates including 2-dimethylaminoethyl methacrylate, 2-morpholinoethyl methacrylate, [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide, and 2-methacryloyloxyethyl phosphorylcholine. Despite the high water content, high end group fidelity is demonstrated by in situ chain extensions and block copolymerizations with PEGMA475 yielding well-defined functional telechelic pentablock copolymers within 2.5 h. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. 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

  10. Self-assembly of micelles in organic solutions of lecithin and bile salt: Mesoscale computer simulation

    Science.gov (United States)

    Markina, A.; Ivanov, V.; Komarov, P.; Khokhlov, A.; Tung, S.-H.

    2016-11-01

    We propose a coarse-grained model for studying the effects of adding bile salt to lecithin organosols by means of computer simulation. This model allows us to reveal the mechanisms of experimentally observed increasing of viscosity upon increasing the bile salt concentration. We show that increasing the bile salt to lecithin molar ratio induces the growth of elongated micelles of ellipsoidal and cylindrical shape due to incorporation of disklike bile salt molecules. These wormlike micelles can entangle into transient network displaying perceptible viscoelastic properties.

  11. Time-resolved fluorescence quenching studies of sodium lauryl ether sulfate micelles

    OpenAIRE

    Friedrich, Leidi C.; Silva, Volnir O.; Moreira Jr, Paulo F.; Tcacenco, Celize M.; Quina, Frank H.

    2013-01-01

    Aggregation numbers (N Ag) of micelles of the commercial anionic detergent sodium lauryl ether sulfate (SLES), with an average of two ethylene oxide subunits, were determined at 30 and 40º C by the time-resolved fluorescence quenching method with pyrene as the fluorescent probe and the N-hexadecylpyridinium ion as the quencher. The added-salt dependent growth of SLES micelles (γ = 0.11-0.15, where γ is the slope of a plot of log aggregation number vs. log [Yaq] and [Yaq] is the sodium counter...

  12. In vivo evaluation of folate decorated cross-linked micelles for the delivery of platinum anticancer drugs.

    Science.gov (United States)

    Eliezar, Jeaniffer; Scarano, Wei; Boase, Nathan R B; Thurecht, Kristofer J; Stenzel, Martina H

    2015-02-09

    The biodistribution of micelles with and without folic acid targeting ligands were studied using a block copolymer consisting of acrylic acid (AA) and polyethylene glycol methyl ether acrylate (PEGMEA) blocks. The polymers were prepared using RAFT polymerization in the presence of a folic acid functionalized RAFT agent. Oxoplatin was conjugated onto the acrylic acid block to form amphiphilic polymers which, when diluted in water, formed stable micelles. In order to probe the in vivo stability, a selection of micelles were cross-linked using 1,8-diamino octane. The sizes of the micelles used in this study range between 75 and 200 nm, with both spherical and worm-like conformation. The effects of cross-linking, folate conjugation and different conformation on the biodistribution were studied in female nude mice (BALB/c) following intravenous injection into the tail vein. Using optical imaging to monitor the fluorophore-labeled polymer, the in vivo biodistribution of the micelles was monitored over a 48 h time-course after which the organs were removed and evaluated ex vivo. These experiments showed that both cross-linking and conjugation with folic acid led to increased fluorescence intensities in the organs, especially in the liver and kidneys, while micelles that are not conjugated with folate and not cross-linked are cleared rapidly from the body. Higher accumulation in the spleen, liver, and kidneys was also observed for micelles with worm-like shapes compared to the spherical micelles. While the various factors of cross-linking, micelle shape, and conjugation with folic acid all contribute separately to prolong the circulation time of the micelle, optimization of these parameters for drug delivery devices could potentially overcome adverse effects such as liver and kidney toxicity.

  13. Enhanced effect of folated pluronic F87-PLA/TPGS mixed micelles on targeted delivery of paclitaxel.

    Science.gov (United States)

    Xiong, Xiang Yuan; Pan, Xiaoqian; Tao, Long; Cheng, Feng; Li, Zi Ling; Gong, Yan Chun; Li, Yu Ping

    2017-10-01

    Targeted drug delivery systems have great potential to overcome the side effect and improve the bioavailability of conventional anticancer drugs. In order to further improve the antitumor efficacy of paclitaxel (PTX) loaded in folated Pluronic F87/poly(lactic acid) (FA-F87-PLA) micelles, D-α-tocopheryl poly(ethylene glycol) 1000 succinate (TPGS or Vitamin E TPGS) were added into FA-F87-PLA to form FA-F87-PLA/TPGS mixed micelles. The LE of PTX-loaded mixed micelles (13.5%) was highest in the mass ratio 5 to 3 of FA-F87-PLA to TPGS. The in vitro cytotoxicity assays indicated that the IC50 values for free PTX injections, PTX-loaded FA-F87-PLA micelles and PTX-loaded FA-F87-PLA/TPGS mixed micelles after 72h of incubation were 1.52, 0.42 and 0.037mg/L, respectively. The quantitative cellular uptake of coumarin 6-loaded FA-F87-PLA/TPGS and FA-F87-PLA micelles showed that the cellular uptake efficiency of mixed micelles was higher for 2 and 4h incubation, respectively. In vivo pharmacokinetic studies found that the AUC of PTX-loaded FA-F87-PLA/TPGS mixed micelles is almost 1.4 times of that of PTX-loaded FA-F87-PLA micelles. The decreased particle size and inhibition of P-glycoprotein effect induced by the addition of TPGS could result in enhancing the cellular uptake and improving the antitumor efficiency of PTX-loaded FA-F87-PLA/TPGS mixed micelles. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. The α-chymotrypsin and its hydrophobic derivatives in inverse micelles; L'α-chymotrypsine et ses derives hydrophobes en micelles inverses

    Energy Technology Data Exchange (ETDEWEB)

    Pitre, Franck

    1993-01-29

    The α-chymotrypsin is among the most used enzymes, notably and particularly in medicine for therapeutic treatments as well as in biochemistry to determine the amine acid sequence of proteins. This research thesis addresses the study of interactions between a micro-emulsion system and an enzymatic system, and more particularly the behaviour of α-chymotrypsin in AOT inverse micelles. After a brief description of the inverse micellar system and of previously obtained results on the solubilisation of α-chymotrypsin in inverse micelles, the author reports the study of the inverse micellar phase in presence of α-chymotrypsin at the vicinity of the maximum solubility. Various techniques are used for this purpose: UV-visible absorption spectrophotometry, conductometry, and X ray scattering. Then, the author describes the chemical modification of α-chymotrypsin, and reports the study of structural as well as reaction modifications introduced during the solubilisation of α-chymotrypsin modified in inverse micelles [French] L'α-chymotrypsine compte parmi les enzymes les plus utilisees dans le monde. Elle est employee tout aussi bien en medecine pour des actions therapeutiques qu'en biochimie afin de determiner entre autre la sequence en acides amines des proteines a etudier. Son succes provient en partie du fait qu'elle hydrolyse avec efficacite un grand nombre de liaisons peptidiques. Les micelles inverses sont un milieu adequat pour permettre l'hydrolyse de molecules relativement hydrophobes par l'α-chymotrypsine. Elle peut ainsi fonctionner dans un milieu tres fortement organique sans etre denaturee. Nous avons montre d'une part que l'α-chymotrypsine se localise au coeur de la micelle inverse sans contact permanent avec les molecules tensioactives. La solubilisation de l'α-chymotrypsine n'a aucune influence sur la taille, pour des micelles dont le rayon est superieur a celui de l'enzyme, et sur le potentiel d'interaction intermicellaire et ceci meme pour des

  15. Studies of bio-mimetic medium of ionic and non-ionic micelles by a simple charge transfer fluorescence probe N,N-dimethylaminonapthyl-(acrylo)-nitrile

    Science.gov (United States)

    Samanta, Anuva; Paul, Bijan Kumar; Guchhait, N.

    2011-05-01

    In this report we have studied micellization process of anionic, cationic and non-ionic surfactants using N,N-dimethylaminonapthyl-(acrylo)-nitrile (DMANAN) as an external fluorescence probe. Micropolarity, microviscosity, critical micellar concentration of these micelles based on steady state absorption and fluorescence and time resolved emission spectroscopy of the probe DMANAN show that the molecule resides in the micelle-water interface for ionic micelles and in the core for the non-ionic micelle. The effect of variation of pH of the micellar solution as well as fluorescence quenching measurements of DMANAN provide further support for the location of the probe in the micelles.

  16. Preparation of a folate-mediated tumor targeting ultraparamagnetic polymeric micelles and its in vitro experimental study

    International Nuclear Information System (INIS)

    Hong Guobin; Zhou Jingxing; Shen Jun; Liang Biling; Yuan Renxu; Shuai Xintao

    2008-01-01

    Objective: To evaluate the tumor targeting characteristic of the Folate-SPIO-DOX- Micelles by in vitro studies, and to test the feasibility of monitor tumor targeting using it and clinical MRI. Methods: The polymeric micelles, Folate-SPIO-DOXO-Micelles were prepared. The in vitro tumor cell targeting efficacy of these folate modified and DOX or SPIO-loaded micelles (Folate-SPIO-DOX- MiceUes) was evaluated by observing the cellular uptake of micelles by human hepatic carcinoma cells (Bel 7402 cells) which overexpressed folate surface receptors. Cell suspensions were incubated with Folate-SPIO- DOXO-Micelles for 1 h. Prussian blue staining was performed to show intracellular irons. Flow cytometry was used to further quantify the cellular uptake of the nanoparticles into Bel 7402 cells. MRI was performed to show the signal intensity changes by using T 2 WI sequences at a clinical 1.5 T MR system. Results Prussian blue staining showed much more intracellular iron in cells incubated with Folate-SPIO-DOX- Micelles than the cells incubated with the non-targeting SPIO-DOX-Micelles. As revealed by flow cytometry, the mean fluorescence intensity of cells in the folate group and the non-folate group were 117.88 and 46. 33, respectively. The T 2 signal intensity in MRI of cells treated with the folate targeting micelles decreased significantly(when the concentration of SPIO in cell culture medium was 5, 10, 20, 40, and 80 μg/ml, respectively, T 2 signal intensity decreased by -5.02%, -23.58%, -45.89%, -70.34%, and -92.41%, respectively). In contrast, T 2 signal intensity did not show obvious decrease for cells treated with the folate-free micelles (when the concentration of SPIO in cell culture medium was at 5, 10, 20, 40, and 80 μg/ml, respectively, T 2 signal intensity decreased by -3.77%, -2.16%, -2.18%, -2.74% and -19.77%, respectively). Conclusion: The polymeric micelles, Folate-SPIO-DOX-Micelles has good targeting ability to the hepatic carcinoma cells in vitro, and

  17. 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.

  18. Reduction-sensitive micelles self-assembled from amphiphilic chondroitin sulfate A-deoxycholic acid conjugate for triggered release of doxorubicin.

    Science.gov (United States)

    Liu, Hongxia; Wu, Shuqin; Yu, Jingmou; Fan, Dun; Ren, Jin; Zhang, Lei; Zhao, Jianguo

    2017-06-01

    Reduction-sensitive chondroitin sulfate A (CSA)-based micelles were developed. CSA was conjugated with deoxycholic acid (DOCA) via a disulfide linkage. The bioreducible conjugate (CSA-ss-DOCA) can form self-assembled micelles in aqueous medium. The critical micelle concentration (CMC) of CSA-ss-DOCA conjugate is 0.047mg/mL, and its mean diameter is 387nm. The anticancer drug doxorubicin (DOX) was chosen as a model drug, and was effectively encapsulated into the micelles with high loading efficiency. Reduction-sensitive micelles and reduction-insensitive control micelles displayed similar DOX release behavior in phosphate buffered saline (PBS, pH7.4). Notably, DOX release from the reduction-sensitive micelles in vitro was accelerated in the presence of 20mM glutathione-containing PBS environment. Moreover, DOX-loaded CSA-ss-DOCA (CSA-ss-DOCA/DOX) micelles exhibited intracellular reduction-responsive characteristics in human gastric cancer HGC-27 cells determined by confocal laser scanning microscopy (CLSM). Furthermore, CSA-ss-DOCA/DOX micelles demonstrated higher antitumor efficacy than reduction-insensitive control micelles in HGC-27 cells. These results suggested that reduction-sensitive CSA-ss-DOCA micelles had the potential as intracellular targeted carriers of anticancer drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Block and Gradient Copoly(2-oxazoline) Micelles: Strikingly Different on the Inside.

    Science.gov (United States)

    Filippov, Sergey K; Verbraeken, Bart; Konarev, Petr V; Svergun, Dmitri I; Angelov, Borislav; Vishnevetskaya, Natalya S; Papadakis, Christine M; Rogers, Sarah; Radulescu, Aurel; Courtin, Tim; Martins, José C; Starovoytova, Larisa; Hruby, Martin; Stepanek, Petr; Kravchenko, Vitaly S; Potemkin, Igor I; Hoogenboom, Richard

    2017-08-17

    Herein, we provide a direct proof for differences in the micellar structure of amphiphilic diblock and gradient copolymers, thereby unambiguously demonstrating the influence of monomer distribution along the polymer chains on the micellization behavior. The internal structure of amphiphilic block and gradient co poly(2-oxazolines) based on the hydrophilic poly(2-methyl-2-oxazoline) (PMeOx) and the hydrophobic poly(2-phenyl-2-oxazoline) (PPhOx) was studied in water and water-ethanol mixtures by small-angle X-ray scattering (SAXS), small-angle neutron scattering (SANS), static and dynamic light scattering (SLS/DLS), and 1 H NMR spectroscopy. Contrast matching SANS experiments revealed that block copolymers form micelles with a uniform density profile of the core. In contrast to popular assumption, the outer part of the core of the gradient copolymer micelles has a distinctly higher density than the middle of the core. We attribute the latter finding to back-folding of chains resulting from hydrophilic-hydrophobic interactions, leading to a new type of micelles that we refer to as micelles with a "bitterball-core" structure.

  20. Analysis of small-angle scattering data from micelles and microemulsions

    DEFF Research Database (Denmark)

    Pedersen, J.S.

    1999-01-01

    The free-form methods for analyzing small-angle scattering data have, during the last years, found more widespread use for micelles and microemulsions. Recent developments have made them applicable also to systems with size polydispersity and particle correlations, however, model fitting still...

  1. An application of micelle solubilization spectrophotometry in the determination of thorium

    International Nuclear Information System (INIS)

    Peng Changhai; Zeng Xiaoming

    1988-01-01

    In this review article the characteristics of the analytical method of Th by means of micelle solubilization spectrophotometry are described and the mechanism of the solubilization and chemical reactions involved is discussed. Also the various color-developing reagents that have been used for this determination are described and compared

  2. Isomerization of Orthogonal Molecular Switches Encapsulated within Micelles Solubilizing Carbon Nanotubes

    DEFF Research Database (Denmark)

    Kreft, Stefanie K.; Petersen, Michael Åxman; Nielsen, Mogens Brøndsted

    2015-01-01

    We study the effects of the proximity of the orthogonal dipole-switching moiety dihydroazulene/vinylheptafulvene (DHA/VHF) to carbon nanotubes (CNTs). The switches are introduced into a micelle surrounding the CNTs, thereby achieving very close proximity between the molecules and the CNTs...... of the CNTs and the resulting reversible redshift of the nanotubes' emission by the change of the molecules' conformation....

  3. Comparison of micelle structure of glycolipids with different head groups by small angle neutron scattering

    International Nuclear Information System (INIS)

    He, Lizhong; Middelberg, Anton; Hartmann, Thorsten; Niemeyer, Bernd; Garamus, V.M.; Willumeit, Regine

    2005-01-01

    Full text: Glycolipids such as n-alkyl- beta-D-glucopyranoside and n-alkyl- beta-D-maltopyranoside can self-assemble into different structures depending on solution conditions. Their amphiphilic properties enable them to serve as biosurfactants in biology and biotechnology, especially for solubilizing membrane proteins. The physicochemical properties of glycolipids have attracted attentions from several research groups, aiming to better understand their application in biological and environmental processes. For example, small angle neutron and X-ray scattering have been used to study micelle structures formed by glycolipids. Our previous work has shown that n-octyl-beta- D-glucopyranoside and n-octyl- beta-D-maltopyranoside form micelles with different structure, suggesting an important role of the sugar head group in micelle formation. In the present work, we further compare micelle structures of n-octyl- beta-Dglucopyranoside and n-octyl- beta-D-galactopyranoside. These two glycolipids have the same hydrophobic tail and their head sugar groups differ only in the conformation with one hydroxyl group pointing to different direction. Our SANS data together with phase behaviours reported by other group have suggested that a slight alteration of head group conformation can significantly affect self-assembly of glycolipids. (authors)

  4. Micelles versus Ribbons: How Congeners Drive the Self-Assembly of Acidic Sophorolipid Biosurfactants.

    Science.gov (United States)

    Dhasaiyan, Prabhu; Le Griel, Patrick; Roelants, Sophie; Redant, Emile; Van Bogaert, Inge N A; Prevost, Sylvain; Prasad, B L V; Baccile, Niki

    2017-03-17

    Sophorolipids (SLs), a class of microbially derived biosurfactants, are reported by different research groups to have different self-assembled structures (either micelles or giant ribbons) under the same conditions. Here we explore the reasons behind these contradictory results and attribute these differences to the role of specific congeners that are present in minute quantities. We show that a sample composed of a majority of oleic acid (C18:1) sophorolipid in the presence of only 0.5 % (or more) of congeners with stearic acid (C18:0) or linoleic acid (C18:2) results in the formation of micelles that are stable over long periods of time. Conversely, the presence of only 10 to 15 % of congeners with a stearic acid chain gives fibrillar structures instead of micelles. To study the mechanisms responsible, oleic acid SLs devoid of any other congeners were prepared. Very interestingly, this sample can self-assemble into either micelles or fibers depending on minute modifications to the self-assembly conditions. The findings are supported by light scattering, small-angle X-ray scattering, transmission electron microscopy under cryogenic conditions, high-pressure liquid chromatography, and NMR spectroscopy. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Specific interactions within micelle microenvironment in different charged dye/surfa

    Directory of Open Access Journals (Sweden)

    Adina Roxana Petcu

    2016-01-01

    Full Text Available The interactions of two ionic dyes, Crystal Violet and Methyl Orange, with different charged surfactants and also with a nonionic surfactant were investigated using surface tension measurements and visible spectroscopy in pre-micellar and post-micellar regions. It was found that for the water dominant phase systems the dye was localized between the polar heads, at the exterior of the direct micelle shells for all the systems. For the oil dominant phase systems, in case of the same charged dye/surfactant couples, the dye was localized in the micelle shell between the hydrocarbon chain of the surfactant nearby the hydrophilic head groups while for nonionic surfactant and oppositely charged dye/surfactant, localization of dye was between the oxyethylenic head groups towards the interior of the micelle core. Mixed aggregates of the dye and surfactant (below the critical micellar concentration of cationic surfactant, dye-surfactant ion pair and surfactant-micelles were present. The values of equilibrium constants (for TX-114/MO and TX-114/CV systems were 0.97 and 0.98, respectively, partition coefficients between the micellar and bulk water phases and standard free energy (for the nonionic systems were −12.59 kJ/mol for MO and −10.97 kJ/mol for CV were calculated for all the studied systems. The partition processes were exothermic and occurred spontaneously.

  6. Time-resolved fluorescence quenching studies of sodium lauryl ether sulfate micelles

    International Nuclear Information System (INIS)

    Friedrich, Leidi C.; Silva, Volnir O.; Quina, Frank H.; Moreira Junior, Paulo F.; Tcacenco, Celize M.

    2013-01-01

    Aggregation numbers (N Ag ) of micelles of the commercial anionic detergent sodium lauryl ether sulfate (SLES), with an average of two ethylene oxide subunits, were determined at 30 and 40 deg C by the time-resolved fluorescence quenching method with pyrene as the fluorescent probe and the N-hexadecylpyridinium ion as the quencher. The added-salt dependent growth of SLES micelles (γ = 0.11-0.15, where γ is the slope of a plot of log aggregation number vs. log [Y aq ] and [Y aq ] is the sodium counterion concentration free in the intermicellar aqueous phase) is found to be significantly lower than that of sodium alkyl sulfate micelles (γ ca. 0.25), a difference attributed to the larger headgroup size of SLES. The I 1 /I 3 vibronic intensity ratio and the rate constant for intramicellar quenching of pyrene show that the pyrene solubilization microenvironment and the intramicellar microviscosity are insensitive to micelle size or the presence of added salt. (author)

  7. Effect of pH on dissociation of casein micelles in yak skim milk.

    Science.gov (United States)

    Yang, M; Zhang, G D; Yang, J T; Sun, D; Wen, P C; Zhang, W B

    2018-04-01

    The dissociation of yak casein (CN) micelles was evaluated by scanning electron microscopy, particle size, fluorescence properties, and soluble mineral and CN molecule content at pH 4.6 to 8.2. The results showed that the size of CN micelles remained constant with decreasing pH from 8.2 to 5.8 but sharply increased at pH ≤5.4. Casein micelles began to aggregate at pH 5.4, and the serum magnesium, potassium, iron, zinc, copper, and manganese levels had their minimum values at this pH level. During acidification, colloidal calcium phosphate dramatically disassociated from yak CN micelles, but the soluble CN monomer content decreased slightly. During alkalization, the soluble calcium and phosphorus content decreased below pH 6.8 but increased with pH increases from 6.8 to 8.2. However, the soluble CN content increased markedly during alkalization. The emission wavelength of 8-anilino-1-naphthalenesulfonic acid sodium salt fluorescence decreased during both acidification and alkalization from pH 6.6, whereas the opposite was found for intrinsic fluorescence. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  8. Constitutive equations for extensional flow of wormlike micelles : stability analysis of the Bautista-Manero model

    NARCIS (Netherlands)

    Boek, E.S.; Padding, J.T.; Anderson, V.J.; Tardy, P.M.J.; Crawshaw, J.P.; Pearson, J.R.A.

    2005-01-01

    We carry out a stability analysis of the Bautista-Manero (B-M) constitutive equations for extensional flow of wormlike micelles. We show that all solutions for the steady-state extensional viscosity ¿E are unstable when the elongational rates e exceed some critical value. In some cases the only real

  9. Core-cross-linked polymeric micelles: a versatile nanomedicine platform with broad applicability

    NARCIS (Netherlands)

    Hu, Q.

    2015-01-01

    This dissertation addresses the broad applicability of the nanomedicine platform core-cross-linked polymeric micelles (CCL-PMs) composed of thermosensitive mPEG-b-pHPMAmLacn block copolymers. In Chapter 1, a general introduction to nanomedicines is provided, with a particular focus on polymeric

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

    Science.gov (United States)

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

    2018-02-15

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

  11. Radiation-induced crosslinking of polymeric micelles as nanoparticle for immobilization of bioactive compound

    International Nuclear Information System (INIS)

    Rida Tajau; Khairul Zaman Mohd Dahlan; Mohd Hilmi Mahmood; Wan Md Zin Wan Yunus; Kamaruddin Hashim; Nor Azowa Ibrahim; Maznah Ismail; Mek Zah Salleh

    2012-01-01

    The purpose of this study was to develop the bioactive-loaded polymeric nanoparticle by radiation-induced crosslinking technique. The polymeric micelles consist of acrylated palm oil (APO), anionic surfactant and aqueous solution was prepared for immobilization of bioactive compound for example the Thymoquinone (TQ). The TQ-loaded APO micelle was subjected to ionizing radiation to induce crosslinked polymeric structure of the TQ-loaded APO nanoparticle. The formation of TQ-loaded APO micro micelle and nano particle were evaluated by the Dynamic Light Scattering (DLS), the Fourier Transform Infrared (FTIR) Spectroscopy and the Transmission Electron Microscopy (TEM) for characterization the size, the shape, the chemical structure and the irradiation effect of the micelle and the nano particle. The results indicate that the size of APO micro and nano particles varies from 120 to 270 nanometer (nm) upon gamma irradiation at doses ranging from 1 to 25 kilo gray (kGy). In addition, size of the particle was found decreasing upon irradiation due to the crosslinking interaction. The study demonstrated that the APO micro-and nanoparticle can retained and controlled the release rate of the thymoquinone at up to 24 hours as determined using ultraviolet-visible (UV-Vis) spectrophotometer. These findings suggested that the ionizing radiation method can be utilized to prepare nano-size APO particles, with the presence of TQ. (author)

  12. New thiol-responsive mono-cleavable block copolymer micelles labeled with single disulfides.

    Science.gov (United States)

    Sourkohi, Behnoush Khorsand; Schmidt, Rolf; Oh, Jung Kwon

    2011-10-18

    Thiol-responsive symmetric triblock copolymers having single disulfide linkages in the middle blocks (called mono-cleavable block copolymers, ss-ABP(2)) were synthesized by atom transfer radical polymerization in the presence of a disulfide-labeled difunctional Br-initiator. These brush-like triblock copolymers consist of a hydrophobic polyacrylate block having pendent oligo(propylene oxide) and a hydrophilic polymethacrylate block having pendent oligo(ethylene oxide). Gel permeation chromatography and (1)H NMR results confirmed the synthesis of well-defined mono-cleavable block copolymers and revealed that polymerizations were well controlled. Because of amphiphilic nature, these copolymers self-assembled to form colloidally stable micelles above critical micellar concentration of 0.032 mg · mL(-1). In response to reductive reactions, disulfides in thiol-responsive micelles were cleaved. Atomic force microscopy and dynamic light scattering analysis suggested that the cleavage of disulfides caused dissociation of micelles to smaller-sized assembled structures in water. Moreover, in a biomedical perspective, the mono-cleavable block copolymer micelles are not cytotoxic and thus biocompatible. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Effect of Admixed Micelles on the Microstructure Alterations of Reinforced Mortar Subjected to Chloride Induced Corrosion

    NARCIS (Netherlands)

    Hu, J.; Koleva, D.A.; Van Breugel, K.

    2011-01-01

    This paper reports the main results from the influence of the initially admixed nano-aggregates (0.5 g/l PEO113-b-PS70 micelles previously dissolved in demi-water) on microstructural alterations of the reinforced mortar subjected to chloride induced corrosion. The morphology of hydration/corrosion

  14. The pressure-induced, lactose-dependent changes in the composition and size of casein micelles.

    Science.gov (United States)

    Wang, Pengjie; Jin, Shaoming; Guo, Huiyuan; Zhao, Liang; Ren, Fazheng

    2015-04-15

    The effects of lactose on the changes in the composition and size of casein micelles induced by high-pressure treatment and the related mechanism of action were investigated. Dispersions of ultracentrifuged casein micelle pellets with 0-10% (w/v) lactose were subjected to high pressure (400 MPa) at 20 °C for 40 min. The results indicated that the level of non-sedimentable caseins was positively related to the amount of lactose added prior to pressure treatment, and negatively correlated to the size. A mechanism for the pressure-induced, lactose-dependent changes in the casein micelles is proposed. Lactose inhibits the hydrophobic interactions between the micellar fragments during or after pressure release, through the hydrophilic layer formed by their hydrogen bonds around the micellar fragments. In addition, lactose does not favour the association between calcium and the casein aggregates after pressure release. Due to these two functions, lactose inhibited the formation of larger micelles after pressure treatment. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Corrosion Performance of Carbon Steel in Simulated Pore Solution in the Presence of Micelles

    NARCIS (Netherlands)

    Hu, J.; Koleva, D.A.; De Wit, J.H.W.; Kolev, H.; Van Breugel, K.

    2011-01-01

    This study presents the results on the investigation of the corrosion behavior of carbon steel in model alkaline medium in the presence of very low concentration of polymeric nanoaggregates [0.0024 wt % polyethylene oxide (PEO)113-b-PS70 micelles]. The steel electrodes were investigated in chloride

  16. Persistence length of wormlike micelles composed of ionic surfactants: self-consistent-field predictions

    NARCIS (Netherlands)

    Lauw, Y.; Leermakers, F.A.M.; Cohen Stuart, M.A.

    2007-01-01

    The persistence length of a wormlike micelle composed of ionic surfactants CnEmXk in an aqueous solvent is predicted by means of the self-consistent-field theory where CnEm is the conventional nonionic surfactant and X-k is an additional sequence of k weakly charged (pH-dependent) segments. By

  17. Novel Brassinosteroid-Modified Polyethylene Glycol Micelles for Controlled Release of Agrochemicals.

    Science.gov (United States)

    Pérez Quiñones, Javier; Brüggemann, Oliver; Kjems, Jørgen; Shahavi, Mohammad Hassan; Peniche Covas, Carlos

    2018-02-21

    Two synthetic analogues of brassinosteroids (DI31 and S7) exhibit good plant growth enhancer activity. However, their hydrophobicity and quick metabolism in plants have limited their application and benefits in agriculture. Our objective was to prepare novel brassinosteroid-modified polyethylene glycol (PEG) micelles to achieve controlled release with extended stability while retaining agrochemical activity. Spectroscopic studies confirmed quantitative disubstitution of studied PEGs with the brassinosteroids, while elemental analysis assessed purity of the synthesized conjugates. Conjugates were also characterized by X-ray diffraction and thermal analysis. Dynamic and static light scattering showed stable and homogeneous approximately spherical micelles with average hydrodynamic diameters of 22-120 nm and almost neutral ζ potential. Spherical 30-140 nm micelles were observed by electron microscopy. Sustained in vitro releases at pH 5.5 were extended up to 96 h. Prepared PEG micelles showed good agrochemical activity in the radish seed bioassay and no cytotoxicity to the human microvascular endothelial cell line in the MTS test.

  18. Hydrolytically degradable polymer micelles for drug delivery: a SAXS/SANS kinetic study

    Czech Academy of Sciences Publication Activity Database

    Filippov, Sergey K.; Franklin, J. M.; Konarev, P. V.; Chytil, Petr; Etrych, Tomáš; Bogomolova, Anna; Dyakonova, M.; Papadakis, C. M.; Radulescu, A.; Ulbrich, Karel; Štěpánek, Petr; Svergun, D. I.

    2013-01-01

    Roč. 14, č. 11 (2013), s. 4061-4070 ISSN 1525-7797 R&D Projects: GA ČR GAP208/10/1600 Institutional support: RVO:61389013 Keywords : HPMA * micelles * drug release Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 5.788, year: 2013

  19. Statistical thermodynamics of association colloids : the equilibrium structure of micelles, vesicles, and bilayer membranes

    NARCIS (Netherlands)

    Leermakers, F.A.M.

    1988-01-01

    The aim of the present study was to unravel the general equilibrium physical properties of lipid bilayer membranes. We consider four major questions:
    1. What determines the morphology of the association colloids (micelles, membranes, vesicles) in general?
    2. Do the

  20. Glutathione responsive micelles incorporated with semiconducting polymer dots and doxorubicin for cancer photothermal-chemotherapy

    Science.gov (United States)

    Cai, Zhixiong; Zhang, Da; Lin, Xinyi; Chen, Yunzhu; Wu, Ming; Wei, Zuwu; Zhang, Zhenxi; Liu, Xiaolong; Yao, Cuiping

    2017-10-01

    Nanoplatform integrated with photothermal therapy (PTT) and chemotherapy has been recognized a promising agent for enhancing cancer therapeutic outcomes, but still suffer from less controllability for optimizing their synergistic effects. We fabricated glutathione (GSH) responsive micelles incorporated with semiconducting polymer dots and doxorubicin (referred as SPDOX NPs) for combining PTT with chemotherapy to enhance cancer therapeutic efficiency. These micelles, with excellent water dispersibility, comprises of three distinct functional components: (1) the monomethoxy-poly(ethylene glycol)-S-S-hexadecyl (mPEG-S-S-C16), which forms the micelles, can render hydrophobic substances water-soluble and improve the colloidal stability; (2) disulfide linkages can be cleaved in a reductive environment for tumor specific drug release due to the high GSH concentrations of tumor micro-environment; (3) PCPDTBT dots and anti-cancer drug DOX that are loaded inside the hydrophobic core of the micelle can be applied to simultaneously perform PTT and chemotherapy to achieve significantly enhanced tumor killing efficiency both in vitro and in vivo. In summary, our studies demonstrated that our SPDOX NPs with simultaneous photothermal-chemotherapy functions could be a promising platform for a tumor specific responsive drug delivery system.

  1. The structure of P85 pluronic block copolymer micelles determined by small-angle neutron scattering

    DEFF Research Database (Denmark)

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

    2003-01-01

    a spherical core of poly(propylene oxide) (PPO) with some water surrounded by a corona of the poly(ethylene oxide) (PEO) block. The latter are non-interacting and obey Gaussian statistics, but are expelled from the core region. The analysis shows that the micelles are fairly concentration and temperature...

  2. Polymeric micelles encapsulating fisetin improve the therapeutic effect in colon cancer.

    Science.gov (United States)

    Chen, Yishan; Wu, Qinjie; Song, Linjiang; He, Tao; Li, Yuchen; Li, Ling; Su, Weijun; Liu, Lei; Qian, Zhiyong; Gong, Changyang

    2015-01-14

    The natural flavonoid fisetin (3,3',4',7-tetrahydroxyflavone) was discovered to possess antitumor activity, revealing its potential value in future chemotherapy. However, its poor water solubility makes it difficult for intravenous administration. In this study, the monomethyl poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) copolymer was applied to prepare nanoassemblies of fisetin by a self-assembly procedure. The prepared fisetin micelles gained a mean particle size of 22 ± 3 nm, polydisperse index of 0.163 ± 0.032, drug loading of 9.88 ± 0.14%, and encapsulation efficiency of 98.53 ± 0.02%. Compared with free fisetin, fisetin micelles demonstrated a sustained and prolonged in vitro release behavior, as well as enhanced cytotoxicity, cellular uptake, and fisetin-induced apoptosis in CT26 cells. As for in vivo studies, fisetin micelles were more competent for suppressing tumor growth and prolonging survival time than free fisetin in the subcutaneous CT26 tumor model. Furthermore, histological analysis, terminal deoxynucleotidyl transferase-mediated nick-end labeling assay, immunohistochemical detection of Ki-67, and microvessel density detection were conducted, demonstrating that fisetin micelles gained increased tumor apoptosis induction, proliferation suppression, and antiangiogenesis activities. In conclusion, we have successfully produced a MPEG-PCL-based nanocarrier encapsulating fisetin with enhanced antitumor activity.

  3. Structural investigation of diglycerol monolaurate reverse micelles in nonpolar oils cyclohexane and octane

    International Nuclear Information System (INIS)

    Shrestha, Lok Kumar; Aramaki, Kenji

    2009-01-01

    Structure of diglycerol monolaurate (abbreviated as C 12 G 2 ) micelles in nonpolar oils cyclohexane and n-octane as a function of compositions, temperatures, and surfactant chain length has been investigated by small-angle X-ray scattering (SAXS). The SAXS data were evaluated by the generalized indirect Fourier transformation (GIFT) method and real-space structural information of particles was achieved. Conventional poly(oxyethylene) type nonionic surfactants do not form reverse micelles in oils unless a trace water is added. However, present surfactant C 12 G 2 formed reverse micelle (RM) in cyclohexane and n-octane without addition of water at normal room temperature. A clear signature of one dimensional (1-D) micellar growth was found with increasing C 12 G 2 concentration. On the other hand, increasing temperature or hydrocarbon chain length of surfactant shorten the length of RM, which is essentially a cylinder-to-sphere type transition in the aggregate structure. Drastic changes in the structure of RM, namely, transition of ellipsoidal prolate to long rod-like micelles was observed upon changing oil from cyclohexane to octane. All the microstructural transitions were explained in terms of critical packing parameter. (author)

  4. The Production of Nanoparticulate Ceria Using Reverse Micelle Sol-Gel Techniques

    Czech Academy of Sciences Publication Activity Database

    Mason, S.; Holliman, P.; Kalaji, M.; Klusoň, Petr

    2009-01-01

    Roč. 19, č. 21 (2009), s. 3517-3522 ISSN 0959-9428 Institutional research plan: CEZ:AV0Z40720504 Keywords : ceria * reverse micelles * alkoxide Subject RIV: CC - Organic Chemistry Impact factor: 4.795, year: 2009

  5. Polymeric micelles with ionic cores containing biodegradable cross-links for delivery of chemotherapeutic agents.

    Science.gov (United States)

    Kim, Jong Oh; Sahay, Gaurav; Kabanov, Alexander V; Bronich, Tatiana K

    2010-04-12

    Novel functional polymeric nanocarriers with ionic cores containing biodegradable cross-links were developed for delivery of chemotherapeutic agents. Block ionomer complexes (BIC) of poly(ethylene oxide)-b-poly(methacylic acid) (PEO-b-PMA) and divalent metal cations (Ca(2+)) were utilized as templates. Disulfide bonds were introduced into the ionic cores by using cystamine as a biodegradable cross-linker. The resulting cross-linked micelles with disulfide bonds represented soft, hydrogel-like nanospheres and demonstrated a time-dependent degradation in the conditions mimicking the intracellular reducing environment. The ionic character of the cores allowed to achieve a very high level of doxorubicin (DOX) loading (50% w/w) into the cross-linked micelles. DOX-loaded degradable cross-linked micelles exhibited more potent cytotoxicity against human A2780 ovarian carcinoma cells as compared to micellar formulations without disulfide linkages. These novel biodegradable cross-linked micelles are expected to be attractive candidates for delivery of anticancer drugs.

  6. Light scattering evidence of selective protein fouling on biocompatible block copolymer micelles

    Czech Academy of Sciences Publication Activity Database

    Giacomelli, F. C.; Štěpánek, Petr; Schmidt, V.; Jäger, Eliezer; Jäger, Alessandro; Giacomelli, C.

    2012-01-01

    Roč. 4, č. 15 (2012), s. 4504-4514 ISSN 2040-3364 R&D Projects: GA ČR GAP208/10/1600 Institutional research plan: CEZ:AV0Z40500505 Keywords : copolymer micelles * protein fouling * light scattering Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 6.233, year: 2012

  7. CTAB/water/chloroform reverse micelles: a closed or open association model?

    Czech Academy of Sciences Publication Activity Database

    Klíčová, L.; Šebej, P.; Štacko, P.; Filippov, Sergey K.; Bogomolova, Anna; Padilla, M.; Klán, P.

    2012-01-01

    Roč. 28, č. 43 (2012), s. 15185-15192 ISSN 0743-7463 R&D Projects: GA ČR GAP108/12/0640 Institutional support: RVO:61389013 Keywords : CTAB * reverse micelles * AFM Subject RIV: CD - Macromolecular Chemistry Impact factor: 4.187, year: 2012

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

    Science.gov (United States)

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

    2010-08-16

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

  9. Tailoring the physicochemical properties of core-crosslinked polymeric micelles for pharmaceutical applications

    Czech Academy of Sciences Publication Activity Database

    Hu, Q.; Rijcken, C. J. F.; van Gaal, E.; Brundel, P.; Kostková, Hana; Etrych, Tomáš; Weber, B.; Barz, M.; Kiessling, F.; Prakash, J.; Storm, G.; Hennink, W. E.; Lammers, T.

    2016-01-01

    Roč. 244, Part B (2016), s. 314-325 ISSN 0168-3659. [European Symposium on Controlled Drug Delivery /14./. Egmond aan Zee, 13.04.2016-15.04.2016] Institutional support: RVO:61389013 Keywords : nanomedicine * drug targeting * polymeric micelles Subject RIV: CD - Macromolecular Chemistry Impact factor: 7.786, year: 2016

  10. 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, Kim Lambertsen

    2009-01-01

    structures. SAXS data show that, at this stage, a decorated micelle links two ACBP molecules together, leaving about half of the polypeptide chain as a disordered region protruding into the solvent. Further titration with SDS leads to the additional uptake of 26 SDS molecules, which, according to SAXS, forms...

  11. Thermodynamic profiling of Peptide membrane interactions by isothermal titration calorimetry: a search for pores and micelles

    DEFF Research Database (Denmark)

    Henriksen, Jonas Rosager; Andresen, Thomas Lars

    2011-01-01

    in mixed peptide-lipid micelles. We have investigated the mode of action of the antimicrobial peptide mastoparan-X using isothermal titration calorimetry (ITC) and cryo-transmission electron microscopy (cryo-TEM). The results show that mastoparan-X induces a range of structural transitions of POPC/POPG (3...

  12. Time-resolved fluorescence quenching studies of sodium lauryl ether sulfate micelles

    Energy Technology Data Exchange (ETDEWEB)

    Friedrich, Leidi C.; Silva, Volnir O.; Quina, Frank H., E-mail: quina@usp.br [Universidade de Sao Paulo (USP), Sao Paulo, SP (Brazil). Instituto de Quimica; Moreira Junior, Paulo F. [Universidade de Sao Paulo (USP), Sao Paulo, SP (Brazil). Escola Politecnica. Departamento de Engenharia Quimica; Tcacenco, Celize M. [Fundacao Instituto de Ensino para Osasco (FIEO/UNIFIEO), SP (Brazil). Centro Universitario FIEO. Centro de Estudos Quimicos

    2013-02-15

    Aggregation numbers (N{sub Ag}) of micelles of the commercial anionic detergent sodium lauryl ether sulfate (SLES), with an average of two ethylene oxide subunits, were determined at 30 and 40 deg C by the time-resolved fluorescence quenching method with pyrene as the fluorescent probe and the N-hexadecylpyridinium ion as the quencher. The added-salt dependent growth of SLES micelles ({gamma} = 0.11-0.15, where {gamma} is the slope of a plot of log aggregation number vs. log [Y{sub aq}] and [Y{sub aq}] is the sodium counterion concentration free in the intermicellar aqueous phase) is found to be significantly lower than that of sodium alkyl sulfate micelles ({gamma} ca. 0.25), a difference attributed to the larger headgroup size of SLES. The I{sub 1}/I{sub 3} vibronic intensity ratio and the rate constant for intramicellar quenching of pyrene show that the pyrene solubilization microenvironment and the intramicellar microviscosity are insensitive to micelle size or the presence of added salt. (author)

  13. Micelle System Based on Molecular Economy Principle for Overcoming Multidrug Resistance and Inhibiting Metastasis.

    Science.gov (United States)

    Qi, Yan; Qin, Xianya; Yang, Conglian; Wu, Tingting; Qiao, Qi; Song, Qingle; Zhang, Zhiping

    2018-03-05

    The high mortality of cancer is mainly attributed to multidrug resistance (MDR) and metastasis. A simple micelle system was constructed here to codeliver doxorubicin (DOX), adjudin (ADD), and nitric oxide (NO) for overcoming MDR and inhibiting metastasis. It was devised based on the "molecular economy" principle as the micelle system was easy to fabricate and exhibited high drug loading efficiency, and importantly, each component of the micelles would exert one or more active functions. DOX acted as the main cell killing agent supplemented with ADD, NO, and d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS). MDR was overcome by synergistic effects of mitochondria inhibition agents, TPGS and ADD. A TPGS-based NO donor can be used as a drug carrier, and it can release NO to enhance drug accumulation and penetration in tumor, resulting in a positive cycle of drug delivery. This DOX-ADD conjugate self-assembly system demonstrated controlled drug release, increased cellular uptake and cytotoxicity, enhanced accumulation at tumor site, and improved in vivo metastasis inhibition of breast cancer. The micelles can fully take advantage of the functions of each component, and they provide a potential strategy for nanomedicine design and clinical cancer treatment.

  14. Intrinsically active nanobody-modified polymeric micelles for tumor-targeted combination therapy

    Czech Academy of Sciences Publication Activity Database

    Talelli, M.; Oliveira, S.; Rijcken, C. J. F.; Pieters, E. H. E.; Etrych, Tomáš; Ulbrich, Karel; van Nostrum, R. C. F.; Storm, G.; Hennink, W. E.; Lammers, T.

    2013-01-01

    Roč. 34, č. 4 (2013), s. 1255-1260 ISSN 0142-9612 R&D Projects: GA AV ČR IAA400500806; GA ČR GAP301/11/0325 Institutional research plan: CEZ:AV0Z40500505 Keywords : polymeric micelle * doxorubicin * active targeting Subject RIV: CD - Macromolecular Chemistry Impact factor: 8.312, year: 2013

  15. Photoenhanced gene transfection by a curcumin loaded CS-g-PZLL micelle.

    Science.gov (United States)

    Lin, Jian-Tao; Pan, Wen-Jia; Zhang, Jun-Ai; Wang, Wei; Zhong, Jia; Su, Jia-Min; Li, Tong; Zou, Ying; Wang, Guan-Hai

    2017-09-01

    The codelivery of drug and gene is a promising method for cancer treatment. In our previous works, we prepared a cationic micelles based on chitosan and poly-(N-3-carbobenzyloxylysine) (CS-g-PZLL), but transfection ratio of CS-g-PZLL to Hela cell was low. Herein, to improve the transfection efficiency of CS-g-PZLL, curcumin was loaded in the CS-g-PZLL micelle. After irradiation, the obtained curcumin loaded micelle showed a better transfection, and the p53 protein expression in Hela cells was higher. The apoptosis assay showed that the complex could induce a more significant apoptosis to Hela cells than that of curcumin or p53 used alone, and the curcumin loaded micelle inducing apoptosis was best after irradiation. Therefore, CS-g-PZLL is a safe and effective carrier for the codelivery of drug/gene, and curcumin could be used as a photosensitizer to induce a photoenhanced gene transfection, which should be encouraged in improving transfection and tumor therapy. Copyright © 2017. Published by Elsevier B.V.

  16. Study of the emission oxidative reactions of ruthenium (II) complex by cationic compounds in anionic micelles

    International Nuclear Information System (INIS)

    Bonilha, J.B.S.

    1985-01-01

    The oxidative quenching of the emission of the tetraanionic complex tris (4,4' dicarboxylate - 2,2' - bipyridine ruthenium (II) in aqueous solution, by both organic and inorganic compounds in presence of anionic detergents, above and below the critical micelle concentration is studied. The organic cations, the inorganic ion and detergents used are shown. (M.J.C.) [pt

  17. Steady state and time-resolved fluorescence spectroscopy of quinine sulfate dication bound to sodium dodecylsulfate micelles: Fluorescent complex formation

    Energy Technology Data Exchange (ETDEWEB)

    Joshi, Sunita; Pant, Debi D., E-mail: ddpant@pilani.bits-pilani.ac.in

    2014-01-15

    Interaction of quinine sulfate dication (QSD) with anionic, sodium dodecylsulphate (SDS) surfactant has been studied at different premicellar, micellar and postmicellar concentrations in aqueous phase using steady state, time-resolved fluorescence and fluorescence anisotropy techniques. At premicellar concentrations of SDS, the decrease in absorbance, appearance of an extra fluorescence band at lower wavelengths and tri-exponential decay behavior of fluorescence, are attributed to complex formation between QSD molecules and surfactant monomers. At postmicellar concentrations the red shift in fluorescence spectrum, increase in quantum yield and increase in fluorescence lifetimes are attributed to incorporation of solute molecules to micelles. At lower concentrations of SDS, a large shift in fluorescence is observed on excitation at the red edge of absorption spectrum and this is explained in terms of distribution of ion pairs of different energies in the ground state and the observed fluorescence lifetime behavior corroborates with this model. The temporal fluorescence anisotropy decay of QSD in SDS micelles allowed determination of restriction on the motion of the fluorophore. All the different techniques used in this study reveal that the photophysics of QSD is very sensitive to the microenvironments of SDS micelles and QSD molecules reside at the water-micelle interface. -- Highlights: • Probe molecule is very sensitive to microenvironment of micelles. • Highly fluorescent ion-pair formation has been observed. • Modulated photophysics of probe molecule in micellar solutions has been observed. • Probe molecules strongly bind with micelles and reside at probe–micelle interface.

  18. Sub-20 nm Stable Micelles Based on a Mixture of Coiled-Coils: A Platform for Controlled Ligand Presentation.

    Science.gov (United States)

    Ang, JooChuan; Ma, Dan; Jung, Benson T; Keten, Sinan; Xu, Ting

    2017-11-13

    Ligand-functionalized, multivalent nanoparticles have been extensively studied for biomedical applications from imaging agents to drug delivery vehicles. However, the ligand cluster size is usually heterogeneous and the local valency is ill-defined. Here, we present a mixed micelle platform hierarchically self-assembled from a mixture of two amphiphilic 3-helix and 4-helix peptide-polyethylene glycol (PEG)-lipid hybrid conjugates. We demonstrate that the local multivalent ligand cluster size on the micelle surface can be controlled based on the coiled-coil oligomeric state. The oligomeric states of mixed peptide bundles were found to be in their individual native states. Similarly, mixed micelles indicate the orthogonal self-association of coiled-coil amphiphiles. Using differential scanning calorimetry, fluorescence recovery spectroscopy, and coarse-grained molecular dynamics simulation, we studied the distribution of coiled-coil bundles within the mixed micelles and observed migration of coiled-coils into nanodomains within the sub-20 nm mixed micelle. This report provides important insights into the assembly and formation of nanophase-separated micelles with precise control over the local multivalent state of ligands on the micelle surface.

  19. Multifunctional doxorubicin/superparamagnetic iron oxide-encapsulated Pluronic F127 micelles used for chemotherapy/magnetic resonance imaging

    Science.gov (United States)

    Lai, Jian-Ren; Chang, Yong-Wei; Yen, Hung-Chi; Yuan, Nai-Yi; Liao, Ming-Yuan; Hsu, Chia-Yen; Tsai, Jai-Lin; Lai, Ping-Shan

    2010-05-01

    Polymeric micelles are frequently used to transport and deliver drugs throughout the body because they protect against degradation. Research on functional polymeric micelles for biomedical applications has generally shown that micelles have beneficial properties, such as specific functionality, enhanced specific tumor targeting, and stabilized nanostructures. The particular aim of this study was to synthesize and characterize multifunctional polymeric micelles for use in controlled drug delivery systems and biomedical imaging. In this study, a theranostic agent, doxorubicin/superparamagnetic iron oxide (SPIO)-encapsulated Pluronic F127 (F127) micelles, was developed for dual chemotherapy/magnetic resonance imaging (MRI) purposes, and the structure and composition of the micellar SPIO were characterized by transmission electron microscopy and magnetic measurements. Our results revealed that the micellar SPIO with a diameter of around 100 nm led to a significant advantage in terms of T2 relaxation as compared with a commercial SPIO contrast agent (Resovist®) without cell toxicity. After doxorubicin encapsulation, a dose-dependent darkening of MR images was observed and HeLa cells were killed by this theranostic micelle. These findings demonstrate that F127 micelles containing chemotherapeutic agents and SPIO could be used as a multifunctional nanocarrier for cancer treatment and imaging.

  20. Conjugation of Lectin to Poly(ε-caprolactone-block-glycopolymer Micelles for In Vitro Intravesical Drug Delivery

    Directory of Open Access Journals (Sweden)

    Ning Ning Li

    2016-10-01

    Full Text Available Amphiphilic poly(ε-caprolactone-block-poly[2-(α-d-mannopyranosyloxy ethyl acrylamide] (PCL-b-PManEA block copolymers were synthesized via a combination of ring-opening polymerization (ROP, reversible addition-fragmentation chain transfer (RAFT polymerization and reactive ester-amine reaction. The PCL-b-PManEA block copolymers can self-assemble into micelles and encapsulate anticancer drug doxorubicin (DOX. To enhance mucoadhesive property of the resulting DOX-loaded PCL-b-PManEA micelles, Concanavalin A (ConA lectin was further conjugated with the micelles. Turbidimetric assay using mucin shows that the DOX-loaded PCL-b-PManEA@ConA micelles are mucoadhesive. DOX release from the DOX-loaded PCL-b-PManEA@ConA micelles in artificial urine at 37 °C exhibits an initial burst release, followed by a sustained and slow release over three days. Confocal laser scanning microscope (CLSM images indicate that the DOX-loaded PCL-b-PManEA@ConA micelles can be effectively internalized by UMUC3 human urothelial carcinoma cells. The DOX-loaded PCL-b-PManEA@ConA micelles exhibit significant cytotoxicity to these cells.