Sample records for 750-labeled phospholipid micelles

  1. Characterization of phospholipid mixed micelles by translational diffusion. (United States)

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


    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 Phi (Phi\\\\ le 15% v/v) of the micelles, experimental measurement of the concentration dependence, combined with use of the D (s)= D (o)(1-3.2lambdaPhi) 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.

  2. Characterization of Phospholipid Mixed Micelles by Translational Diffusion

    Energy Technology Data Exchange (ETDEWEB)

    Chou, James J. [Harvard Medical School, Department of Biological Chemistry and Molecular Pharmacology (United States); Baber, James L.; Bax, Ad [National Institutes of Health, Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases (United States)], E-mail:


    The concentration dependence of the translational self diffusion rate, D{sub 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 {phi} ({phi} {<=} 15% v/v) of the micelles, experimental measurement of the concentration dependence, combined with use of the D{sub s}=D{sub o}(1-3.2{lambda}{phi}) relationship, yields the hydrodynamic volume. For proteins, the hydrodynamic volume, derived from D{sub 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 {sup 15}N relaxation data.

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

    DEFF Research Database (Denmark)

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


    Knowledge about colloidal assemblies present in human intestinal fluids (HIFs), such as bile salt micelles and phospholipid vesicles, is regarded of importance for a better understanding of the in vivo dissolution and absorption behavior of poorly soluble drugs (Biopharmaceutics Classification...... distinct size fraction of colloidal assemblies, whereas FeSSIF contained 2 fractions of colloidal species with significantly different sizes. These size fractions likely represent (1) mixed taurocholate-phospholipid-micelles, as indicated by a size range up to 70 nm (in diameter) and a strong UV absorption...... sizes of approximately 50 and 200 nm, respectively (intensity-weighted mean diameter, Dz), likely representing mixed cholate/phospholipid micelles and phospholipid vesicles, respectively. The sizes of the smaller 2 fractions being below the size range of multiangle laser light scattering analysis (

  4. Mixed micelle formation between amino acid-based surfactants and phospholipids. (United States)

    Faustino, Célia M C; Calado, António R T; Garcia-Rio, Luís


    The mixed micelle formation in aqueous solutions between an anionic gemini surfactant derived from the amino acid cystine (C(8)Cys)(2), and the phospholipids 1,2-diheptanoyl-sn-glycero-3-phosphocholine (DHPC, a micelle-forming phospholipid) and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC, a vesicle-forming phospholipid) has been studied by conductivity and the results compared with the ones obtained for the mixed systems with the single-chain surfactant derived from cysteine, C(8)Cys. Phospholipid-surfactant interactions were found to be synergistic in nature and dependent on the type of phospholipid and on surfactant hydrophobicity. Regular solution theory was used to analyse the gemini surfactant-DHPC binary mixtures and the interaction parameter, β(12), has been evaluated, as well as mixed micelle composition. The results have been interpreted in terms of the interplay between reduction of the electrostatic repulsions among the ionic head groups of the surfactants and steric hindrances arising from incorporation of the zwitterionic phospholipids in the mixed micelles.

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

    Zhang, Sha; Wang, Xiaoyong


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

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

    DEFF Research Database (Denmark)

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


    in detergent micelles and phospholipid bilayers. In the presence of EGF, catalytically active EGFR dimers can be isolated by gel filtration in dodecyl maltoside. Visualization of the dimeric species by negative stain electron microscopy and single particle averaging reveals an overall structure...

  7. Cytotoxicity Study on Luminescent Nanocrystals Containing Phospholipid Micelles in Primary Cultures of Rat Astrocytes (United States)

    Valente, Gianpiero; Fanizza, Elisabetta; Laquintana, Valentino; Denora, Nunzio; Fasano, Anna; Striccoli, Marinella; Colella, Matilde; Agostiano, Angela; Curri, M. Lucia; Liuzzi, Grazia Maria


    Luminescent colloidal nanocrystals (NCs) are emerging as a new tool in neuroscience field, representing superior optical probes for cellular imaging and medical diagnosis of neurological disorders with respect to organic fluorophores. However, only a limited number of studies have, so far, explored NC applications in primary neurons, glia and related cells. Indeed astrocytes, as resident cells in the central nervous system (CNS), play an important pathogenic role in several neurodegenerative and neuroinflammatory diseases, therefore enhanced imaging tools for their thorough investigation are strongly amenable. Here, a comprehensive and systematic study on the in vitro toxicological effect of core-shell type luminescent CdSe@ZnS NCs incorporated in polyethylene glycol (PEG) terminated phospholipid micelles on primary cultures of rat astrocytes was carried out. Cytotoxicity response of empty micelles based on PEG modified phospholipids was compared to that of their NC containing counterpart, in order to investigate the effect on cell viability of both inorganic NCs and micelles protecting NC surface. Furthermore, since the surface charge and chemistry influence cell interaction and toxicity, effect of two different functional groups terminating PEG-modified phospholipid micelles, namely amine and carboxyl group, respectively, was evaluated against bare micelles, showing that carboxyl group was less toxic. The ability of PEG-lipid micelles to be internalized into the cells was qualitatively and quantitatively assessed by fluorescence microscopy and photoluminescence (PL) assay. The results of the experiments clearly demonstrate that, once incorporated into the micelles, a low, not toxic, concentration of NCs is sufficient to be distinctly detected within cells. The overall study provides essential indications to define the optimal experimental conditions to effectively and profitably use the proposed luminescent colloidal NCs as optical probe for future in vivo

  8. Slow Phospholipid Exchange between a Detergent-Solubilized Membrane Protein and Lipid-Detergent Mixed Micelles: Brominated Phospholipids as Tools to Follow Its Kinetics (United States)

    Montigny, Cédric; Dieudonné, Thibaud; Orlowski, Stéphane; Vázquez-Ibar, José Luis; Gauron, Carole; Georgin, Dominique; Lund, Sten; le Maire, Marc; Møller, Jesper V.; Champeil, Philippe


    Membrane proteins are largely dependent for their function on the phospholipids present in their immediate environment, and when they are solubilized by detergent for further study, residual phospholipids are critical, too. Here, brominated phosphatidylcholine, a phospholipid which behaves as an unsaturated phosphatidylcholine, was used to reveal the kinetics of phospholipid exchange or transfer from detergent mixed micelles to the environment of a detergent-solubilized membrane protein, the paradigmatic P-type ATPase SERCA1a, in which Trp residues can experience fluorescence quenching by bromine atoms present on phospholipid alkyl chains in their immediate environment. Using dodecylmaltoside as the detergent, exchange of (brominated) phospholipid was found to be much slower than exchange of detergent under the same conditions, and also much slower than membrane solubilization, the latter being evidenced by light scattering changes. The kinetics of this exchange was strongly dependent on temperature. It was also dependent on the total concentration of the mixed micelles, revealing the major role for such exchange of the collision of detergent micelles with the detergent-solubilized protein. Back-transfer of the brominated phospholipid from the solubilized protein to the detergent micelle was much faster if lipid-free DDM micelles instead of mixed micelles were added for triggering dissociation of brominated phosphatidylcholine from the solubilized protein, or in the additional presence of C12E8 detergent during exchange, also emphasizing the role of the chemical nature of the micelle/protein interface. This protocol using brominated lipids appears to be valuable for revealing the possibly slow kinetics of phospholipid transfer to or from detergent-solubilized membrane proteins. Independently, continuous recording of the activity of the protein can also be used in some cases to correlate changes in activity with the exchange of a specific phospholipid, as shown here

  9. Two distinct mechanisms of vesicle-to-micelle and micelle-to-vesicle transition are mediated by the packing parameter of phospholipid-detergent systems

    NARCIS (Netherlands)

    Stuart, Marc C. A.; Boekema, Egbert J.


    The detergent solubilization and reformation of phospholipid vesicles was studied for various detergents. Two distinct mechanisms of vesicle-to-micelle and micelle-to-vesicle transition were observed by turbidimetry and cryo-electron microscopy. The first mechanism involves fast solubilization of ph

  10. Phospholipid containing mixed micelles. Characterization of diheptanoyl phosphatidylcholine (DHPC) and sodium dodecyl sulfate and DHPC and dodecyl trimethylammonium bromide. (United States)

    Ranganathan, Radha; Vautier-Giongo, Carolina; Bakshi, Mandeep Singh; Bales, Barney L; Hajdu, Joseph


    Mixed micelles of l,2-diheptanoyl-sn-grycero-3-phosphocholine (DHPC) with ionic detergents were prepared to develop well characterized substrates for the study of lipolytic enzymes. The aggregates that formed on mixing DHPC with the anionic surfactant sodium dodecyl sulfate (SDS) and with the positively charged dodecyl trimethylammonium bromide (DTAB) were investigated using time-resolved fluorescence quenching (TRFQ) to determine the aggregation numbers and bimolecular collision rates, and electron spin resonance (ESR) to measure the hydration index and microviscosity of the micelles at the micelle-water interface. Mixed micelles between the phospholipid and each of the detergents formed in all compositions, yielding interfaces with varying charge, hydration, and microviscosity. Both series of micelles were found to be globular up to 0.7 mole fraction of DHPC, while the aggregation numbers varied within the same concentration range of the components less than 15%. Addition of the zwitterionic phospholipid component increased the degree of counterion dissociation as measured by the quenching of the fluorescence of pyrene by the bromide ions bound to DHPC/DTAB micelles, showing that at 0.6 mole fraction of DHPC 80% of the bromide ions are dissociated from the micelles. The interface water concentration decreased significantly on addition of DHPC to each detergent. For combined phospholipid and detergent concentration of 50 mM the interface water concentration decreased, as measured by ESR of the spin-probes, from 38.5 M/L of interface volume in SDS alone to 9 M/L when the phospholipid was present at 0.7 mole fraction. Similar addition of DHPC to DTAB decreased the interfacial water concentration from 27 M/L to 11 M/L. Determination of the physicochemical parameters of the phospholipid containing mixed micelles here presented are likely to provide important insight into the design of assay systems for kinetic studies of phospholipid metabolizing enzymes.

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

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    Dong F


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

  12. Structure of the integrin beta3 transmembrane segment in phospholipid bicelles and detergent micelles. (United States)

    Lau, Tong-Lay; Partridge, Anthony W; Ginsberg, Mark H; Ulmer, Tobias S


    Integrin adhesion receptors transduce bidirectional signals across the plasma membrane, with the integrin transmembrane domains acting as conduits in this process. Here, we report the first high-resolution structure of an integrin transmembrane domain. To assess the influence of the membrane model system, structure determinations of the beta3 integrin transmembrane segment and flanking sequences were carried out in both phospholipid bicelles and detergent micelles. In bicelles, a 30-residue linear alpha-helix, encompassing residues I693-H772, is adopted, of which I693-I721 appear embedded in the hydrophobic bicelle core. This relatively long transmembrane helix implies a pronounced helix tilt within a typical lipid bilayer, which facilitates the snorkeling of K716's charged side chain out of the lipid core while simultaneously immersing hydrophobic L717-I721 in the membrane. A shortening of bicelle lipid hydrocarbon tails does not lead to the transfer of L717-I721 into the aqueous phase, suggesting that the reported embedding represents the preferred beta3 state. The nature of the lipid headgroup affected only the intracellular part of the transmembrane helix, indicating that an asymmetric lipid distribution is not required for studying the beta3 transmembrane segment. In the micelle, residues L717-I721 are also embedded but deviate from linear alpha-helical conformation in contrast to I693-K716, which closely resemble the bicelle structure.

  13. Phosphatidylcholine reverse micelles on the wrong track in molecular dynamics simulations of phospholipids in an organic solvent (United States)

    Vierros, S.; Sammalkorpi, M.


    Here, we examine a well-characterized model system of phospholipids in cyclohexane via molecular dynamics simulations using a force field known for reproducing both phospholipid behavior in water and cyclohexane bulk properties to a high accuracy, CHARMM36, with the aim of evaluating the transferability of a force field parametrization from an aqueous environment to an organic solvent. We compare the resulting reverse micelles with their expected experimental shape and size, and find the model struggles with reproducing basic, experimentally known reverse micellar structural characteristics for common phosphadidylcholine lipids such as 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC), 1,2-dioleyl-sn-glycero-3-phosphatidylcholine (DOPC), and 1,2-dilinoleyl-sn-glycero-3-phosphatidylcholine (DLPC) in cyclohexane solvent. We find evidence that the deviation from the experimental behavior originates from an underestimation of the lipid tail-cyclohexane interaction in the model. We compensate for this, obtain reverse micellar structures within the experimentally expected range, and characterize these structurally in molecular detail. Our findings indicate extra caution and verification of model applicability is warranted in simulational studies employing standard biomolecular models outside the usual aqueous environment.

  14. Slow Phospholipid Exchange between a Detergent-Solubilized Membrane Protein and Lipid-Detergent Mixed Micelles Brominated Phospholipids as Tools to Follow Its Kinetics

    DEFF Research Database (Denmark)

    Montigny, Cédric; Dieudonné, Thibaud; Orlowski, Stéphane


    Membrane proteins are largely dependent for their function on the phospholipids present in their immediate environment, and when they are solubilized by detergent for further study, residual phospholipids are critical, too. Here, brominated phosphatidylcholine, a phospholipid which behaves as an ...

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

    Directory of Open Access Journals (Sweden)

    Shen R


    Full Text Available Roger Shen,1 Jane J Kim,2 Mingyi Yao,2,3 Tamer A Elbayoumi2,3 1Department of Family Medicine, Northeastern Health Systems-Tahlequah City Hospital, Tahlequah, OK, USA; 2Department of Pharmaceutical Sciences, College of Pharmacy-Glendale, Midwestern University, 3Nanomedicine Center of Excellence in Translational Nanomedicine, Midwestern University, Glendale, AZ, USA Abstract: Berberine (Brb is an active alkaloid occurring in various common plant species, with well-recognized potential for cancer therapy. Brb not only augments the efficacy of antineoplastic chemotherapy and radiotherapy but also exhibits direct antimitotic and proapoptotic actions, along with distinct antiangiogenic and antimetastatic activities in a variety of tumors. Despite its low systemic toxicity, several pharmaceutical challenges limit the application of Brb in cancer therapy (ie, extremely low solubility and permeability, very poor pharmacokinetics (PKs, and oral bioavailability. Among lipid-based nanocarriers investigated recently for Brb, stealth amphiphilic micelles of polymeric phospholipid conjugates were studied here as a promising strategy to improve Brb delivery to tumors. Specifically, physicochemically stable micelles made of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol-2000] (PEG-PE mixed with D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS (PEG-succinate ester of vitamin E, in a 3:1 M ratio, increased Brb solubilization by 300%. Our PEG-PE/TPGS-mixed micelles firmly retained the incorporated Brb, displaying extended-release profile in simulated media, with up to 30-fold projected improvement in simulated PKs of Brb. Owing to the markedly better uptake of Brb-containing mixed micelles in vitro, our Brb-mixed micelles nanoformulation significantly amplified apoptosis and overall cytotoxic effectiveness against monolayer and spheroid cultures of human prostate carcinomas (16- to 18-fold lower half-maximal inhibitory

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

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


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

  17. 21 CFR 358.750 - Labeling of drug products for the control of dandruff, seborrheic dermatitis, or psoriasis. (United States)


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

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

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    Lv QY


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

  19. Small angle X-ray scattering and 31P NMR studies on the phase behavior of phospholipid bilayered mixed micelles (United States)

    Bolze, Jörg; Fujisawa, Tetsuro; Nagao, Takashi; Norisada, Kazushi; Saitô, Hazime; Naito, Akira


    The phase behavior of lipid bilayered micelles (`bicelles') (dimyristoyl-phosphatidylcholine, DMPC/dihexanoyl-phosphatidyl-choline, DHPC 2.6/1) has been studied by small angle X-ray scattering and 31P NMR. Below 3% w/v the bilayers are arranged in tightly packed stacks. At intermediate concentrations single units are observed, whereas at 24% w/v and higher, weak stacking occurs again. The DMPC/DHPC ratio in the bicelles strongly increases at low concentration, which is correlated with an increase in the bicelle size and stacking. The increase of the order parameter in a magnetic field is related to the stack formation. Below 297 K there is no stacking at any concentration and no magnetic alignment.

  20. Micelles Hydrodynamics

    CERN Document Server

    Svintradze, David V


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

  1. Applications of micelle enhancement in luminescence-based analysis. (United States)

    Alarfaj, Nawal A; El-Tohamy, Maha F


    Micelles are self-assembled aggregates that arrange themselves into spheres in aqueous media. When the surfactant concentration reaches the critical micelle concentration, extensive aggregation of the surfactant monomers occurs to form micelles. A micelle has both a hydrophilic and a hydrophobic part. This allows them to form a spherical shape and for their glycolipid and phospholipid components to form lipid bilayers. The importance of micelles is increasing because of their wide analytical applications. Recently, colloidal carrier systems have received much attention in the field of analytical chemistry, especially in luminescence enhancement applications.

  2. Role of phospholipids in the pathophysiology of the gut-liver axis

    NARCIS (Netherlands)

    Petruzzelli, M.


    Phospholipids represent essential components of bile. Together with bile acids and cholesterol, phospholipids form “mixed micelles”. If sufficient amounts of phospholipids are available, no simple bile acid micelles are present, with prevention of bile acid toxicity and cholesterol crystallization.

  3. [Preparation and characterization of cucurbitacin B sodium deoxycholate/phospholipid-mixed oral fast dissolving film and antitumor activity study]. (United States)

    Yu, Chao; Xiao, Yun-Zhi; Xun, Ping-Hua; Dai, Ling; Han, Jin; Yuan, Hai-Long


    A novel drug delivery system combining oral fast dissolving film with sodium deoxycholate/phospholipid mixed micelles was prepared to increase the absorption of cucurbitacin B that is a poor aqueous solubility substance. Encapsulation efficiency, particle size, zeta potential, polydispersity coefficient, investigated the morphology, disintegration time of oral fast dissolving film and the pharmacodynamic properties of cucurbitacin B sodium deoxycholate/phospholipid-mixed micelles before and after solidified in mice were evaluated and compared. The oral fast dissolving film prepared in this study showed a homogeneous pale yellow and could completely disintegrated in the 30 s. It could meet the requirements of rapidly disintegrating fully. The encapsulation efficiency, particle size, zeta potential, polydispersity coefficient of cucurbitacin B sodium deoxycholate/phospholipid-mixed micelles loaded in oral fast dissolving film were (43.36 +/- 2.12)%, (108.82 +/- 5.2) nm, (-34.18 +/- 1.07) mV, 0.088 +/- 0.012, respectively. The encapsulation efficiency, particle size, zeta potential, polydispersity coefficient of cucurbitacin B sodium deoxycholate/phospholipid-mixed micelles in solution were (41.26 +/- 2.22)%, (181.82 +/- 4.48) nm, (-30.67 +/- 0.81) mV, 0.092 +/- 0.012, respectively. The difference of pharmacodynamics among film of cucurbitacin B-loaded micelles, cucurbitacin B-loaded micelles and free cucurbitacin B in vivo was compared. Solubility of cucurbitacin B loaded in sodium deoxycholate/phospholipid-mixed micelles has also been greatly improved. The tumor inhibition rate of cucurbitacin B loaded in sodium deoxycholate/phospholipid-mixed micelles was significantly improved and did not change significantly before and after solidified. These showed that the sodium deoxycholate/phospholipid-mixed micelles could enhance the antitumor activities of cucurbitacin B and the stability of cucurbitacin B sodium deoxycholate/phospholipid-mixed micelles was improved

  4. Molecular interactions between bile salts, phospholipids and cholesterol : relevance to bile formation, cholesterol crystallization and bile salt toxicity

    NARCIS (Netherlands)

    Moschetta, Antonio


    Cholesterol is a nonpolar lipid dietary constituent, absorbed from the small intestine, transported in blood and taken up by the liver. In bile, the sterol is solubilized in mixed micelles by bile salts and phospholipids. In case of supersaturation, cholesterol is kept in vesicles with phospholipid

  5. A review on phospholipids and their main applications in drug delivery systems

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    Jing Li


    Full Text Available Phospholipids have the characteristics of excellent biocompatibility and a especial amphiphilicity. These unique properties make phospholipids most appropriate to be employed as important pharmaceutical excipients and they have a very wide range of applications in drug delivery systems. The aim of this review is to summarize phospholipids and some of their related applications in drug delivery systems, and highlight the relationship between the properties and applications, and the effect of the species of phospholipids on the efficiency of drug delivery. We refer to some relevant literatures, starting from the structures, main sources and properties of phospholipids to introduce their applications in drug delivery systems. The present article focuses on introducing five types of carriers based on phospholipids, including liposomes, intravenous lipid emulsions, micelles, drug-phospholipids complexes and cochleates.

  6. The aminosterol antibiotic squalamine permeabilizes large unilamellar phospholipid vesicles. (United States)

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


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

  7. Complex coacervate core micelles. (United States)

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


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

  8. CHARMM-GUI micelle builder for pure/mixed micelle and protein/micelle complex systems. (United States)

    Cheng, Xi; Jo, Sunhwan; Lee, Hui Sun; Klauda, Jeffery B; Im, Wonpil


    Micelle Builder in CHARMM-GUI, , is a web-based graphical user interface to build pure/mixed micelle and protein/micelle complex systems for molecular dynamics (MD) simulation. The robustness of Micelle Builder is tested by simulating four detergent-only homogeneous micelles of DHPC (dihexanoylphosphatidylcholine), DPC (dodecylphosphocholine), TPC (tetradecylphosphocholine), and SDS (sodium dodecyl sulfate) and comparing the calculated micelle properties with experiments and previous simulations. As a representative protein/micelle model, Pf1 coat protein is modeled and simulated in DHPC micelles with three different numbers of DHPC molecules. While the number of DHPC molecules in direct contact with Pf1 protein converges during the simulation, distinct behavior and geometry of micelles lead to different protein conformations in comparison to that in bilayers. It is our hope that CHARMM-GUI Micelle Builder can be used for simulation studies of various protein/micelle systems to better understand the protein structure and dynamics in micelles as well as distribution of detergents and their dynamics around proteins.

  9. Anionic phospholipids modulate peptide insertion into membranes. (United States)

    Liu, L P; Deber, C M


    While the insertion of a hydrophobic peptide or membrane protein segment into the bilayer can be spontaneous and driven mainly by the hydrophobic effect, anionic lipids, which comprise ca. 20% of biological membranes, provide a source of electrostatic attractions for binding of proteins/peptides into membranes. To unravel the interplay of hydrophobicity and electrostatics in the binding of peptides into membranes, we designed peptides de novo which possess the typical sequence Lys-Lys-Ala-Ala-Ala-X-Ala-Ala-Ala-Ala-Ala-X-Ala-Ala-Trp-Ala-Ala-X-Ala-Al a-Ala-Lys-Lys-Lys-Lys-amide, where X residues correspond to "guest" residues which encompass a range of hydrophobicity (Leu, Ile, Gly, and Ser). Circular dichroism spectra demonstrated that peptides were partially (40-90%) random in aqueous buffer but were promoted to form 100% alpha-helical structures by anionic lipid micelles. In neutral lipid micelles, only the relatively hydrophobic peptides (X = L and I) spontaneously adopted the alpha-helical conformation, but when 25% of negatively charged lipids were mixed in to mimic the content of anionic lipids in biomembranes, the less hydrophobic (X = S and G) peptides then formed alpha-helical conformations. Consistent with these findings, fluorescence quenching by the aqueous-phase quencher iodide indicated that in anionic (dimyristoylphosphatidylglycerol) vesicles, the peptide Trp residue was buried in the lipid vesicle hydrophobic core, while in neutral (dimyristoylphosphatidylcholine) vesicles, only hydrophobic (X = L and I) peptides were shielded from the aqueous solution. Trp emission spectra of peptides in the presence of phospholipids doxyl-labeled at the 5-, 7-, 10-, 12-, and 16-fatty acid positions implied not only a transbilayer orientation for inserted peptides but also that mixed peptide populations (transbilayer + surface-associated) may arise. Overall results suggest that for hydrophobic peptides with segmental threshold hydrophobicity below that which

  10. Micellar lipid composition affects micelle interaction with class B scavenger receptor extracellular loops. (United States)

    Goncalves, Aurélie; Gontero, Brigitte; Nowicki, Marion; Margier, Marielle; Masset, Gabriel; Amiot, Marie-Josèphe; Reboul, Emmanuelle


    Scavenger receptors (SRs) like cluster determinant 36 (CD36) and SR class B type I (SR-BI) play a debated role in lipid transport across the intestinal brush border membrane. We used surface plasmon resonance to analyze real-time interactions between the extracellular protein loops and various ligands ranging from single lipid molecules to mixed micelles. Micelles mimicking physiological structures were necessary for optimal binding to both the extracellular loop of CD36 (lCD36) and the extracellular loop of SR-BI (lSR-BI). Cholesterol, phospholipid, and fatty acid micellar content significantly modulated micelle binding to and dissociation from the transporters. In particular, high phospholipid micellar concentrations inhibited micelle binding to both receptors (-53.8 and -74.4% binding at 0.32 mM compared with 0.04 mM for lCD36 and lSR-BI, respectively, P < 0.05). The presence of fatty acids was crucial for micelle interactions with both proteins (94.4 and 81.3% binding with oleic acid for lCD36 and lSR-BI, respectively, P < 0.05) and fatty acid type substitution within the micelles was the component that most impacted micelle binding to the transporters. These effects were partly due to subsequent modifications in micellar size and surface electric charge, and could be correlated to micellar vitamin D uptake by Caco-2 cells. Our findings show for the first time that micellar lipid composition and micellar properties are key factors governing micelle interactions with SRs.

  11. Polymerization of anionic wormlike micelles. (United States)

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


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

  12. Mammalian P4-ATPases and ABC transporters and their role in phospholipid transport. (United States)

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


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

  13. Enzymatic reactions in reversed micelles

    NARCIS (Netherlands)

    Hilhorst, M.H.


    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 micellar enzymo

  14. Enzyme recovery using reversed micelles.

    NARCIS (Netherlands)

    Dekker, M.


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

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

    DEFF Research Database (Denmark)

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


    Asolectin phospholipid nano-microfibers were prepared using electrospinning processing. The asolectin fibers were studied by scanning electron microscopy, and the fiber morphology was found to be strongly dependent on the phospholipid concentration and the solvents used. The solvents studied were...... does not follow the theoretically predicted value of similar to 0.35 mu m because of the intermolecular aggregation between the reverse micelles formed in the highly concentrated asolectin solutions. However, when co-axial solvent electrospinning was applied, where the outer needle contains a pure...

  16. Supercritical fluid reverse micelle separation (United States)

    Fulton, John L.; Smith, Richard D.


    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.

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

    Directory of Open Access Journals (Sweden)

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


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

  18. Lysophosphatidylcholine enhances carotenoid uptake from mixed micelles by Caco-2 human intestinal cells. (United States)

    Sugawara, T; Kushiro, M; Zhang, H; Nara, E; Ono, H; Nagao, A


    Despite the interest in the beneficial roles of dietary carotenoids in human health, little is known about their solubilization from foods to mixed bile micelles during digestion and the intestinal uptake from the micelles. We investigated the absorption of carotenoids solubilized in mixed micelles by differentiated Caco-2 human intestinal cells, which is a useful model for studying the absorption of dietary compounds by intestinal cells. The micelles were composed of 1 micromol/L carotenoids, 2 mmol/L sodium taurocholate, 100 micromol/L monoacylglycerol, 33.3 micromol/L fatty acid and phospholipid (0-200 micromol/L). The phospholipid content of micelles had profound effects on the cellular uptake of carotenoids. Uptake of micellar beta-carotene and lutein was greatly suppressed by phosphatidylcholine (PC) in a dose-dependent manner, whereas lysophosphatidylcholine (lysoPC), the lipolysis product of PC by phospholipase A2 (PLA2), markedly enhanced both beta-carotene and lutein uptake. The addition of PLA2 from porcine pancreas to the medium also enhanced the uptake of carotenoids from micelles containing PC. Caco-2 cells could take up 15 dietary carotenoids, including epoxy carotenoids, such as violaxanthin, neoxanthin and fucoxanthin, from micellar carotenoids, and the uptakes showed a linear correlation with their lipophilicity, defined as the distribution coefficient in 1-octanol/water (log P(ow)). These results suggest that pancreatic PLA2 and lysoPC are important in regulating the absorption of carotenoids in the digestive tract and support a simple diffusion mechanism for carotenoid absorption by the intestinal epithelium.

  19. Solution structure and phospholipid interactions of the isolated voltage-sensor domain from KvAP. (United States)

    Butterwick, Joel A; MacKinnon, Roderick


    Voltage-sensor domains (VSDs) are specialized transmembrane segments that confer voltage sensitivity to many proteins such as ion channels and enzymes. The activities of these domains are highly dependent on both the chemical properties and the physical properties of the surrounding membrane environment. To learn about VSD-lipid interactions, we used nuclear magnetic resonance spectroscopy to determine the structure and phospholipid interface of the VSD from the voltage-dependent K(+) channel KvAP (prokaryotic Kv from Aeropyrum pernix). The solution structure of the KvAP VSD solubilized within phospholipid micelles is similar to a previously determined crystal structure solubilized by a nonionic detergent and complexed with an antibody fragment. The differences observed include a previously unidentified short amphipathic α-helix that precedes the first transmembrane helix and a subtle rigid-body repositioning of the S3-S4 voltage-sensor paddle. Using (15)N relaxation experiments, we show that much of the VSD, including the pronounced kink in S3 and the S3-S4 paddle, is relatively rigid on the picosecond-to-nanosecond timescale. In contrast, the kink in S3 is mobile on the microsecond-to-millisecond timescale and may act as a hinge in the movement of the paddle during channel gating. We characterized the VSD-phospholipid micelle interactions using nuclear Overhauser effect spectroscopy and showed that the micelle uniformly coats the KvAP VSD and approximates the chemical environment of a phospholipid bilayer. Using paramagnetically labeled phospholipids, we show that bilayer-forming lipids interact with the S3 and S4 helices more strongly than with S1 and S2.

  20. Phospholipidic Monolayers on Formamide (United States)

    Graner, François; Perez-Oyarzun, Santiago; Saint-Jalmes, Arnaud; Flament, Cyrille; Gallet, François


    We report the first phase diagram of a Langmuir film at the air-formamide interface. Stable films of phospholipids such as DPPC or DSPC undergo phase transitions observed on isotherms or by fluorescence microscopy. They display bidimensional gas, liquid and solid phases, as well as two mesophases; the latter coexist with liquid on a sharp first-order transition plateau. We compare these observations with known results on films on water. Nous présentons le premier diagramme de phase d'un film de Langmuir à l'interface air-formamide. On observe, sur des isothermes et par microscopie de fluorescence, des transitions de phase dans des films stables de phospholipides comme le DPPC ou le DSPC. Cinq phases bidimensionnelles sont mises en évidence : gaz, liquide, solide, ainsi que deux mésophases ; ces deux dernières coexistent avec le liquide sur un plateau très marqué de transition du premier ordre. Nous comparons ces observations avec les résultats connus pour les films sur l'eau.

  1. Synthesis of Photoactivatable Phospholipidic Probes

    Institute of Scientific and Technical Information of China (English)

    Qing PENG; Fan Qi QU; Yi XIA; Jie Hua ZHOU; Qiong You WU; Ling PENG


    We synthesized and characterized photoactivatable phospholipidic probes 1-3. These probes have the perfluorinated aryl azide function at the polar head of phospholipid. They are stable in dark and become highly reactive upon photoirradiation. The preliminary results suggest that they are promising tools to study the topology of membrane proteins and protein-lipid interactions using photolabeling approach.

  2. Oxidative stability of marine phospholipids

    DEFF Research Database (Denmark)

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

    Many studies have shown that marine phospholipids (MPL) provide more advantages than fish oil. They have better bioavailability, better resistance towards oxidation and higher content of eicosapentaenoic acids (EPA) and docosahexaenoic acids (DHA) than oily triglycerides (fish oil). The objective...

  3. Cell signalling and phospholipid metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Boss, W.F.


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

  4. Structural analysis of bacteriorhodopsin solubilized by lipid-like phosphocholine biosurfactants with varying micelle concentrations. (United States)

    Wang, Xiaoqiang; Huang, Haihong; Sun, Chenghao; Huang, Fang


    Surfactants that can provide a more natural substitute for lipid bilayers are important in the purification and in vitro study of membrane proteins. Here we investigate the structural response of a model membrane protein, bacteriorhodopsin (BR), to phosphocholine biosurfactants. Phosphocholine biosurfactants are a type of biomimetic amphiphile that are similar to phospholipids, in which membrane proteins are commonly embedded. Multiple spectroscopic and zeta potential measurements are employed to characterize the conformational change, secondary and tertiary structure, oligomeric status, surface charge distribution and the structural stability of BR solubilized with phosphocholine biosurfactants of varying tail length. The process of phosphocholine micelle formation is found to facilitate the solubilization of BR, and for long-chain phosphocholines, concentrations much higher than their critical micelle concentrations achieve good solubilization. Phosphocholine biosurfactants are shown to be mild compared with the ionic surfactant SDS or CTAB, and tend to preserve membrane protein structure during solubilization, especially at low micelle concentrations, by virtue of their phospholipid-like zwitterionic head groups. The increase of alkyl chain length is shown to obviously enhance the capability of phosphocholine biosurfactants to stabilize BR. The underlying mechanism for the favorable actions of phosphocholine biosurfactant is also discussed.

  5. Interactions of amelogenin with phospholipids. (United States)

    Lokappa, Sowmya Bekshe; Chandrababu, Karthik Balakrishna; Dutta, Kaushik; Perovic, Iva; Evans, John Spencer; Moradian-Oldak, Janet


    Amelogenin protein has the potential to interact with other enamel matrix proteins, mineral, and cell surfaces. We investigated the interactions of recombinant amelogenin rP172 with small unilamellar vesicles as model membranes, toward the goal of understanding the mechanisms of amelogenin-cell interactions during amelogenesis. Dynamic light scattering (DLS), fluorescence spectroscopy, circular dichroism (CD), and nuclear magnetic resonance (NMR) were used. In the presence of phospholipid vesicles, a blue shift in the Trp fluorescence emission maxima of rP172 was observed (∼334 nm) and the Trp residues of rP172 were inaccessible to the aqueous quencher acrylamide. DLS studies indicated complexation of rP172 and phospholipids, although the possibility of fusion of phospholipids following amelogenin addition cannot be ruled out. NMR and CD studies revealed a disorder-order transition of rP172 in a model membrane environment. Strong fluorescence resonance energy transfer from Trp in rP172 to DNS-bound-phospholipid was observed, and fluorescence polarization studies indicated that rP172 interacted with the hydrophobic core region of model membranes. Our data suggest that amelogenin has ability to interact with phospholipids and that such interactions may play key roles in enamel biomineralization as well as reported amelogenin signaling activities.

  6. Molecular Simulation of Reverse Micelles (United States)

    Chowdhary, Janamejaya; Ladanyi, Branka


    Reverse micelles (RM) are surfactant assemblies containing a nanosized water pool dissolved in a hydrophobic solvent. Understanding their properties is crucial for insight into the effect of confinement on aqueous structure, dynamics as well as physical processes associated with solutes in confinement. We perform molecular dynamics simulations for the RM formed by the surfactant Aerosol-OT (AOT) in isooctane (2,2,4-trimethyl pentane) in order to study the effect of reverse micelle size on the aqueous phase. The structure of the RM is quantified in terms of the radial and pair density distributions. Dynamics are studied in terms of the mean squared displacements and various orientational time correlation functions in different parts of the RM so as to understand the effect of proximity to the interface on aqueous dynamics. Shape fluctuations of the RM are also analyzed.

  7. Ultrasound-Mediated Polymeric Micelle Drug Delivery. (United States)

    Xia, Hesheng; Zhao, Yue; Tong, Rui


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

  8. Phospholipids in foods: prooxidants or antioxidants? (United States)

    Cui, Leqi; Decker, Eric A


    Lipid oxidation is one of the major causes of quality deterioration in natural and processed foods and thus a large economic concern in the food industry. Phospholipids, especially lecithins, are already widely used as natural emulsifiers and have been gaining increasing interest as natural antioxidants to control lipid oxidation. This review summarizes the fatty acid composition and content of phospholipids naturally occurring in several foods. The role of phospholipids as substrates for lipid oxidation is discussed, with a focus on meats and dairy products. Prooxidant and antioxidant mechanisms of phospholipids are also discussed to get a better understanding of the possible opportunities for using phospholipids as food antioxidants.

  9. Bacterial phospholipide antigens and their taxonomic significance. (United States)

    Karalnik, B V; Razbash, M P; Akhmetova, E A


    The investigation of interrelationships between the phospholipides of various microorganisms (33 strains of corynebacteria, mycobacteria and staphylococci) using crossed antibody neutralization reactions with phospholipide antigenic erythrocyte diagnostic was used for the assessment of the degree of antigenic propinquity and antigenic differences between the phospholipides of bacteria of the same species, genus, and of different genera. The role of the determinants of the corresponding (their own) and "foreign" genera in the antigenic differences between the phospholipides of the microorganisms investigated was established. On the basis of the results obtained the conclusion has been drawn that the method of assessment of antigenic interrelationships between phospholipides can be used for the study of some taxonomic problems.

  10. Formation of micelles with complex coacervate cores.

    NARCIS (Netherlands)

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


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

  11. Stable Polymer Micelles Formed by Metal Coordination

    NARCIS (Netherlands)

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


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

  12. Synthesis of photolabile fluorescent polymeric micelles. (United States)

    Park, Teahoon; You, Jungmok; Oikawa, Hidetoshi; Kim, Eunkyoung


    A new amphiphilic block copolymers were synthesized with the atom transfer radical polymerization (ATRP) method. Then, the micelle structures were fabricated with a self-assembly method for application in nanocarriers and sensing. The fluorescent intensity was increased by a factor of 4 in the micelle solution due to more stacked pyrene moieties. The core-shell structure of the micelle was confirmed by HR-TEM images. The pyrene moieties were positioned in the core of the micelle, and the surface consisted of hydrophilic PMMA blocks. The ester bond of the polymer backbone was breakable by irradiation with UV light. Therefore, the micelle structure was deformed after UV irradiation, and the excimer peak was drastically reduced as the monomer peak appeared. The deformation of micelle structures was clearly confirmed by FE-SEM and NMR analysis. These photolabile polymeric micelles may be widely useful for photo-stimulative nanocarriers as well as for the design of new functional micelles with many other chromophores.

  13. Nanomechanics of electrospun phospholipid fiber

    DEFF Research Database (Denmark)

    Mendes, Ana Carina Loureiro; Nikogeorgos, Nikolaos; Lee, Seunghwan;


    Electrospun asolectin phospholipid fibers were prepared using isooctane as a solvent and had an average diameter of 6.1 +/- 2.7 mu m. Their mechanical properties were evaluated by nanoindentation using Atomic Force Microscopy, and their elastic modulus was found to be approximately 17.2 +/- 1MPa....... At a cycle of piezo expansion-retraction (loading-unloading) of a silicon tip on a fiber, relatively high adhesion was observed during unloading. It is proposed that this was primarily due to molecular rearrangements at the utmost layers of the fiber caused by the indentation of the hydrophilic tip....... The phospholipid fibers were shown to be stable in ambient conditions, preserving the modulus of elasticity up to 24 h. (c) 2015 AIP Publishing LLC....

  14. Nanomechanics of electrospun phospholipid fiber

    Energy Technology Data Exchange (ETDEWEB)

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


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

  15. [Bile phospholipids; function and significance]. (United States)

    Salvioli, G; Salati, R


    The part played by phospholipides in the genesis of cholesterol gallstone considered. This is present in patients who frequently present a lecithin synthesis defect at hepatic level since precursors are used for forming triglycerides. Nevertheless polyunsaturated phosphatidicholine has a negative influence on the SB + PL/C ratio in the bile of T-tube subjects receiving 2 g of substance i.v. for 5 days.

  16. Polar Solvents Trigger Formation of Reverse Micelles. (United States)

    Khoshnood, Atefeh; Firoozabadi, Abbas


    We use molecular dynamics simulations and molecular thermodynamics to investigate the formation of reverse micelles in a system of surfactants and nonpolar solvents. Since the early observation of reverse micelles, the question has been whether the existence of polar solvent molecules such as water is the driving force for the formation of reverse micelles in nonpolar solvents. In this work, we use a simple coarse-grained model of surfactants and solvents to show that a small number of polar solvent molecules triggers the formation of large permanent aggregates. In the absence of polar molecules, both the thermodynamic model and molecular simulations show that small aggregates are more populated in the solution and larger ones are less frequent as the system evolves over time. The size and shape of reverse micelles depend on the size of the polar core: the shape is spherical for a large core and ellipsoidal for a smaller one. Using the coarse-grained model, we also investigate the effect of temperature and surfactant tail length. Our results reveal that the number of surfactant molecules in the micelle decreases as the temperature increases, but the average diameter does not change because the size of the polar core remains invariant. A reverse micelle with small polar core attracts fewer surfactants when the tail is long. The uptake of solvent particles by a micelle of longer surfactant tail is less than shorter ones when the polar solvent particles are initially distributed randomly.

  17. Chemical reactions in reverse micelle systems (United States)

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


    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.

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

    Directory of Open Access Journals (Sweden)

    Krishna Vukoti

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

  19. Characterization of magnetically oriented phospholipid micelles for measurement of dipolar couplings in macromolecules. (United States)

    Ottiger, M; Bax, A


    Weak alignment of solute molecules with the magnetic field can be achieved in a dilute liquid crystalline medium, consisting of an aqueous mixture of dimyristoyl-phosphatidylcholine (DMPC) and dihexanoyl-phosphatidylcholine (DHPC). For a certain range of molar ratios, DMPC and DHPC can form large, disc-shaped particles, commonly referred to as bicelles (Sanders and Schwonek, 1992), which cooperatively align in the magnetic field and induce a small degree of alignment on asymmetrically shaped solute molecules. As a result, dipolar couplings between pairs of 1H, 13C or 15N nuclei are no longer averaged to zero by rotational diffusion and they can be readily measured, providing valuable structural information. The stability of these liquid crystals and the degree of alignment of the solute molecules depend strongly on experimental variables such as the DMPC:DHPC ratio and concentration, the preparation protocol of the DMPC/DHPC mixtures, as well as salt, temperature, and pH. The lower temperature limit for which the liquid crystalline phase is stable can be reduced to 20 degrees C by using a ternary mixture of DHPC, DMPC, and 1-myristoyl-2-myristoleoyl-sn-glycero-3-phosphocholine, or a binary mixture of DHPC and ditridecanoyl-phosphatidylcholine. These issues are discussed, with an emphasis on the use of the medium for obtaining weak alignment of biological macromolecules.

  20. Characterization of magnetically oriented phospholipid micelles for measurement of dipolar couplings in macromolecules

    Energy Technology Data Exchange (ETDEWEB)

    Ottiger, Marcel; Bax, Ad [National Institutes of Health, Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases (United States)


    Weak alignment of solute molecules with the magnetic field can be achieved in a dilute liquid crystalline medium, consisting of an aqueous mixture of dimyristoyl-phosphatidylcholine (DMPC) and dihexanoyl-phosphatidylcholine (DHPC). For a certain range of molar ratios, DMPC and DHPC can form large, disc-shaped particles, commonly referred to as bicelles (Sanders and Schwonek, 1992), which cooperatively align in the magnetic field and induce a small degree of alignment on asymmetrically shaped solute molecules. As a result, dipolar couplings between pairs of {sup 1}H, {sup 13}C or {sup 15}N nuclei are no longer averaged to zero by rotational diffusion and they can be readily measured, providing valuable structural information. The stability of these liquid crystals and the degree of alignment of the solute molecules depend strongly on experimental variables such as the DMPC:DHPC ratio and concentration, the preparation protocol of the DMPC/DHPC mixtures, as well as salt, temperature, and pH. The lower temperature limit for which the liquid crystalline phase is stable can be reduced to 20 deg. C by using a ternary mixture of DHPC, DMPC, and 1-myristoyl-2-myristoleoyl-sn-glycero-3-phosphocholine, or a binary mixture of DHPC and ditridecanoyl-phosphatidylcholine. These issues are discussed, with an emphasis on the use of the medium for obtaining weak alignment of biological macromolecules.

  1. Formation of substrate-supported membranes from mixtures of long- and short-chain phospholipids. (United States)

    Morigaki, Kenichi; Kimura, Shigeki; Okada, Keisuke; Kawasaki, Takashi; Kawasaki, Kazunori


    We studied the formation of substrate-supported planar phospholipid bilayers (SPBs) on glass and silica from mixtures of long- and short-chain phospholipids to assess the effects of detergent additives on SPB formation. 1,2-Hexyanoyl-sn-glycero-3-phosphocholine (DHPC-C6) and 1,2-heptanoyl-sn-glycero-3-phosphocholine (DHPC-C7) were chosen as short-chain phospholipids. 1-Palmitoyl-2-oleol-sn-glycero-3-phosphocholine (POPC) was used as a model long-chain phospholipid. Kinetic studies by quartz crystal microbalance with dissipation monitoring (QCM-D) showed that the presence of short-chain phospholipids significantly accelerated the formation of SPBs. Rapid rinsing with a buffer solution did not change the adsorbed mass on the surface if POPC/DHPC-C6 mixtures were used below the critical micelle concentration (cmc) of DHPC-C6, indicating that an SPB composed of POPC molecules remained on the surface. Fluorescence microscopy observation showed homogeneous SPBs, and the fluorescence recovery after photobleaching (FRAP) measurements gave a diffusion coefficient comparable to that for SPBs formed from POPC vesicles. However, mixtures of POPC/DHPC-C7 resulted in a smaller mass of lipid adsorption on the substrate. FRAP measurements also yielded significantly smaller diffusion coefficients, suggesting the presence of defects. The different behaviors for DHPC-C6 and DHPC-C7 point to the dual roles of detergents to enhance the formation of SPBs and to destabilize them, depending on their structures and aggregation properties.

  2. Micelle Catalysis of an Aromatic Substitution Reaction (United States)

    Corsaro, Gerald; Smith J. K.


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

  3. Polysaccharide-Based Micelles for Drug Delivery

    Directory of Open Access Journals (Sweden)

    Nan Zhang


    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.

  4. Casein Micelle Dispersions under Osmotic Stress


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


    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 press...

  5. Nonionic reverse micelles near the critical point. (United States)

    Shrestha, Lok Kumar; Shrestha, Rekha Goswami


    We report shape, size, and internal cross-sectional structure of diglycerol monomyristate (C₁₄G₂) reverse micelles in n-hexadecane near the critical point using small-angle X-ray scattering (SAXS). Pair-distance distribution function, p(r), which gives structural information in real-space, was obtained by indirect Fourier transformation (IFT) method. The p(r) showed a clear picture of rodlike micelles at higher temperatures well above the critical point (micellar solution phase separates into two immiscible liquids at ~ 48°C). At a fixed surfactant concentration (5% C₁₄G₂), decrease in temperature increases the micellar size monotonously and surprisingly shape of the p(r) curve at 50°C; close to the critical point, mimics the shape of the two dimensional disk-like micelles indicating the onset of critical fluctuations (attractive interactions among rodlike micelles forming a weak network). A similar behavior has been observed with normal micelles in aqueous system near the critical point. When the system is heated to 60°C, shape of the p(r) curve regains rodlike structure. At fixed temperature of 60°C, increase in C₁₄G₂ concentration induced one dimensional micellar growth. Maximum length of micelles increases from ca. 23.5 to 46.0 nm upon increasing concentration from 1 to 12% keeping cross section diameter apparently unchanged at ca. 4.0 nm.

  6. Polymeric micelles for acyclovir drug delivery. (United States)

    Sawdon, Alicia J; Peng, Ching-An


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

  7. Phospholipid liposomes functionalized by protein (United States)

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


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

  8. Phospholipid Vesicles in Materials Science

    Energy Technology Data Exchange (ETDEWEB)

    Granick, Steve [Univ. of Illinois, Champaign, IL (United States)


    The objective of this research was to develop the science basis needed to deploy phospholipid vesicles as functional materials in energy contexts. Specifically, we sought to: (1) Develop an integrated molecular-level understanding of what determines their dynamical shape, spatial organization, and responsiveness to complex, time-varying environments; and (2) Develop understanding of their active transportation in crowded environments, which our preliminary measurements in cells suggest may hold design principles for targeting improved energy efficiency in new materials systems. The methods to do this largely involved fluorescence imaging and other spectroscopy involving single particles, vesicles, particles, DNA, and endosomes. An unexpected importance outcome was a new method to image light-emitting diodes during actual operation using super-resolution spectroscopy.

  9. Connexin channels and phospholipids: association and modulation

    Directory of Open Access Journals (Sweden)

    Harris Andrew L


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

  10. Molecular Exchange in Ordered Diblock Copolymer Micelles (United States)

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


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

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


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


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


    Directory of Open Access Journals (Sweden)

    M. S. Santos

    Full Text Available Abstract Surfactants are amphiphilic molecules that can spontaneously self-assemble in solution, forming structures known as micelles. Variations in temperature, pH, and electrolyte concentration imply changes in the interactions between surfactants and micelle stability conditions, including micelle size distribution and micelle shape. Here, molecular thermodynamics is used to describe and predict conditions of micelle formation in surfactant solutions by directly calculating the minimum Gibbs free energy of the system, corresponding to the most stable condition of the surfactant solution. In order to find it, the proposed methodology takes into account the micelle size distribution and two possible geometries (spherical and spherocylindrical. We propose a numerical optimization methodology where the minimum free energy can be reached faster and in a more reliable way. The proposed models predict the critical micelle concentration well when compared to experimental data, and also predict the effect of salt on micelle geometry transitions.

  13. Mitochondrial phospholipids: role in mitochondrial function. (United States)

    Mejia, Edgard M; Hatch, Grant M


    Mitochondria are essential components of eukaryotic cells and are involved in a diverse set of cellular processes that include ATP production, cellular signalling, apoptosis and cell growth. These organelles are thought to have originated from a symbiotic relationship between prokaryotic cells in an effort to provide a bioenergetic jump and thus, the greater complexity observed in eukaryotes (Lane and Martin 2010). Mitochondrial processes are required not only for the maintenance of cellular homeostasis, but also allow cell to cell and tissue to tissue communication (Nunnari and Suomalainen 2012). Mitochondrial phospholipids are important components of this system. Phospholipids make up the characteristic outer and inner membranes that give mitochondria their shape. In addition, these membranes house sterols, sphingolipids and a wide variety of proteins. It is the phospholipids that also give rise to other characteristic mitochondrial structures such as cristae (formed from the invaginations of the inner mitochondrial membrane), the matrix (area within cristae) and the intermembrane space (IMS) which separates the outer mitochondrial membrane (OMM) and inner mitochondrial membrane (IMM). Phospholipids are the building blocks that make up these structures. However, the phospholipid composition of the OMM and IMM is unique in each membrane. Mitochondria are able to synthesize some of the phospholipids it requires, but the majority of cellular lipid biosynthesis takes place in the endoplasmic reticulum (ER) in conjunction with the Golgi apparatus (Fagone and Jackowski 2009). In this review, we will focus on the role that mitochondrial phospholipids play in specific cellular functions and discuss their biosynthesis, metabolism and transport as well as the differences between the OMM and IMM phospholipid composition. Finally, we will focus on the human diseases that result from disturbances to mitochondrial phospholipids and the current research being performed to help

  14. Coal desulfurization through reverse micelle biocatalysis process

    Energy Technology Data Exchange (ETDEWEB)

    Lee, K.; Yen, T.F.


    A novel bioprocess using micelle biocatalysis has been attempted to minimize several disadvantages of conventional microbial coal desulfurization scale-up processes. The reverse micelle biocatalysis process consists of a water-immiscible organic medium, a surfactant, an aqueous phase and sulfur-oxidizing bacteria or enzymes. This process has been successful for removing sulfur from bituminous coal (Illinois coal 5). The preliminary results showed that coal desulfurization through the use of cell-free enzyme extracts of Thiobacillus ferrooxidans ATCC 19859 was better than that of bacteria itself. The use of enzymes has shown potential for commercial coal desulfurization process as well. This same process is being applied to the thermophillic bacteria Sulfolobus acidocaldarius ATCC 33909. The implications of these experimental results are discussed, including a hypothetical mechanism using reverse micelle biocatalytical process for coal desulfurization.

  15. Mechanism of Molecular Exchange in Copolymer Micelles (United States)

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


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

  16. Lipid peroxidation generates biologically active phospholipids including oxidatively N-modified phospholipids. (United States)

    Davies, Sean S; Guo, Lilu


    Peroxidation of membranes and lipoproteins converts "inert" phospholipids into a plethora of oxidatively modified phospholipids (oxPL) that can act as signaling molecules. In this review, we will discuss four major classes of oxPL: mildly oxygenated phospholipids, phospholipids with oxidatively truncated acyl chains, phospholipids with cyclized acyl chains, and phospholipids that have been oxidatively N-modified on their headgroups by reactive lipid species. For each class of oxPL we will review the chemical mechanisms of their formation, the evidence for their formation in biological samples, the biological activities and signaling pathways associated with them, and the catabolic pathways for their elimination. We will end by briefly highlighting some of the critical questions that remain about the role of oxPL in physiology and disease.

  17. Salt-induced release of lipase from polyelectrolyte complex micelles

    NARCIS (Netherlands)

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


    With the aim to gain insight into the possible applicability of protein-filled polyelectrolyte complex micelles under physiological salt conditions, we studied the behavior of these micelles as a function of salt concentration. The micelles form by electrostatically driven co-assembly from strong ca

  18. Stability of casein micelles in milk (United States)

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


    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.

  19. Statistical crystallography of surface micelle spacing (United States)

    Noever, David A.


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

  20. Polymeric micelles as carriers of diagnostic agents. (United States)



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

  1. Molecular phospholipid films on solid supports

    DEFF Research Database (Denmark)

    Czolkos, Ilja; Jesorka, Aldo; Orwar, Owe


    Phospholipid membranes are versatile structures for mimicking biological surfaces. Bilayer and monolayer membranes can be formed on solid supports, leading to enhanced stability and accessibility of the biomimetic molecular film. This has facilitated functional studies of membrane proteins...

  2. Storage stability of marine phospholipids emulsions

    DEFF Research Database (Denmark)

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

    Marine phospholipids (MPL) are believed to provide more advantages than fish oil from the same source. They are considered to have a better bioavailability, a better resistance towards oxidation and a higher content of polyunsaturated fatty acids such as eicosapentaenoic (EPA) and docosahexaenoic...... of secondary volatile compounds by Solid Phase Microextraction at several time intervals at 2°C storage. Preliminary results showed that marine phospholipids emulsion has a good oxidative stability....

  3. Cell signalling and phospholipid metabolism. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Boss, W.F.


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

  4. Gravimetric determination of phospholipid concentration. (United States)

    Tejera-Garcia, Roberto; Connell, Lisa; Shaw, Walter A; Kinnunen, Paavo K J


    Accurate determination of lipid concentrations is an obligatory routine in a research laboratory engaged in studies using this class of biomaterials. For phospholipids, this is frequently accomplished using the phosphate assay (Bartlett, G.R. Phosphorus Assay in Column Chromatography. J. Biol. Chem. 234, 466-468, 1959). Given the purity of the currently commercially available synthetic and isolated natural lipids, we have observed that determination of the dry weight of lipid stock solutions provides the fastest, most accurate, and generic method to assay their concentrations. The protocol described here takes advantage of the high resolution and accuracy obtained by modern weighing technology. We assayed by this technique the concentrations of a number of phosphatidylcholine samples, with different degrees of acyl chain saturation and length, and in different organic solvents. The results were compared with those from Bartlett assay, (31)P NMR, and Langmuir compression isotherms. The data obtained show that the gravimetric assay yields lipid concentrations with a resolution similar or better than obtained by the other techniques.

  5. Enzymatic modification of phospholipids forfunctional applications and human nutrition

    DEFF Research Database (Denmark)

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


    Rapid progress in biochemistry of phospholipids and evolution of modern bioengineering has brought forth a number of novel concepts and technical advancements in the modification of phospholipids for industrial applications and human nutrition. Highlights cover preparation of novel phospholipid...... analogs based on the latest understanding of pivotal role of phospholipids in manifold biological processes, exploration of remarkable application potentials of phospholipids in meliorating human health, as well as development of new chemical and biotechnological approaches applied to the modification...

  6. Spectroscopic studies of interaction of Safranine T with nonionic micelles and mixed micelles. (United States)

    Chatterjee, Sujan; Bhattacharya, Subhash Chandra


    The visible spectra of Safranine T (ST) in micellar solution of Brij 58, Tween 20 and Tween 40 and mixed micellar solution of Brij 58/Tween 20 and Brij 58/Tween 40 indicate formation of 1:1 charge transfer (CT) complex between acceptor ST and donor nonionic micelles and mixed micelles. The experimental CT transition energies are well correlated (through Mulliken's equation) with the vertical ionization potential of the donors. The solvent parameters, i.e. the intramolecular charge transfer energy ET(30) have been determined from the Stokes spectral shift. Variations of ionization potential and micropolarity in the mixed micellar region have been investigated as a function of surfactant composition and the obtained results in mixed micellar medium has been compared to the normal micelles. The critical micelle concentration (CMC) values determined at various surfactant compositions are lower than the ideal values indicating a synergistic interaction. The interaction parameter (beta) and micellar stability has been calculated using regular solution theory.

  7. Micelle depletion-induced vs. micelle-mediated aggregation in nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Ray, D., E-mail:; Aswal, V. K. [Solid State Physics Division, Bhabha Atomic Research Centre, Mumbai 400 085 (India)


    The phase behavior anionic silica nanoparticle (Ludox LS30) with non-ionic surfactants decaethylene glycol monododecylether (C12E10) and cationic dodecyltrimethyl ammonium bromide (DTAB) in aqueous electrolyte solution has been studied by small-angle neutron scattering (SANS). The measurements have been carried out for fixed concentrations of nanoparticle (1 wt%), surfactants (1 wt%) and electrolyte (0.1 M NaCl). Each of these nanoparticle–surfactant systems has been examined for different contrast conditions where individual components (nanoparticle or surfactant) are made visible. It is observed that the nanoparticle-micelle system in both the cases lead to the aggregation of nanoparticles. The aggregation is found to be micelle depletion-induced for C12E10 whereas micelle-mediated aggregation for DTAB. Interestingly, it is also found that phase behavior of mixed surfactant (C12E10 + DTAB) system is similar to that of C12E10 (unlike DTAB) micelles with nanoparticles.

  8. Self-assembling micelle-like nanoparticles with detachable envelopes for enhanced delivery of nucleic acid therapeutics. (United States)

    Battogtokh, Gantumur; Ko, Young Tag


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

  9. SANS analysis of aqueous ionic perfluoropolyether micelles

    CERN Document Server

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


    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.)


    NARCIS (Netherlands)



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

  11. On the composition fluctuations of reverse micelles. (United States)

    Tovstun, Sergey A; Razumov, Vladimir F


    The polydispersity of the reverse micelles is determined mainly by the fluctuations of their composition. The composition of the reverse micelle is a two-dimensional random variable whose components are the numbers of water (i) and surfactant (j) molecules. In this study the fluctuations of the composition of the reverse micelles are considered in the Gaussian approximation. It is shown that the standard deviation of the quantity w=i/j may be calculated from the dependence of the water vapor pressure above the microemulsion on the molar ratio W=[water]/[surfactant]. The estimation based on the literature data for microemulsion system sodium bis(2-ethylhexyl)sulfosuccinate/water/isooctane at 37°C in the range W=0-18 has shown that the relative standard deviation of the quantity w is about 10%. It is shown that the value of the composition fluctuations is related to the dependence of average composition on the concentration of reverse micelles at constant parameter W.

  12. Molecular Exchange Dynamics in Block Copolymer Micelles (United States)

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


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

  13. Chain exchange in block copolymer micelles (United States)

    Lu, Jie; Bates, Frank; Lodge, Timothy


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

  14. Non-diffusing radiochromic micelle gel (United States)

    Jordan, Kevin; Sekimoto, Masaya


    The addition of Laponite, a synthetic clay nanoparticle material to radiochromic leuco Malachite Green micelle hydrogel eliminates diffusion of the cationic dye by electrostatic binding. The clay nanoparticles also increased dose sensitivity ten-fold relative to the parent gel formulation. This material is a suitable 3D water equivalent dosimeter with optical CT readout.

  15. Casein micelles and their internal structure

    Energy Technology Data Exchange (ETDEWEB)

    De Kruif, Cornelis G [ORNL; Huppertz, Thom [NIZO Food Research; Urban, Volker S [ORNL; Petukhov, Andrei V [Van ' t Hoff laboratory for Physical and Colloid Chemistry, Utrecht University, The Netherlands


    The internal structure of casein micelles was studied by calculating the small-angle neutron and X-ray scattering and static light scattering spectrum (SANS, SAXS, SLS) as a function of the scattering contrast and composition. We predicted experimental SANS, SAXS, SLS spectra self consistently using independently determined parameters for composition size, polydispersity, density and voluminosity. The internal structure of the casein micelles, i.e. how the various components are distributed within the casein micelle, was modeled according to three different models advocated in the literature; i.e. the classical sub-micelle model, the nanocluster model and the dual binding model. In this paper we present the essential features of these models and combine new and old experimental SANS, SAXS, SLS and DLS scattering data with new calculations that predict the spectra. Further evidence on micellar substructure was obtained by internally cross linking the casein micelles using transglutaminase, which led to casein nanogel particles. In contrast to native casein micelles, the nanogel particles were stable in 6 M urea and after sequestering the calcium using trisodium citrate. The changed scattering properties were again predicted self consistently. An important result is that the radius of gyration is independent of contrast, indicating that the mass distribution within a casein micelle is homogeneous. Experimental contrast is predicted quite well leading to a match point at a D{sub 2}O volume fraction of 0.41 ratio in SANS. Using SANS and SAXS model calculations it is concluded that only the nanocluster model is capable of accounting for the experimental scattering contrast variation data. All features and trends are predicted self consistently, among which the 'famous' shoulder at a wave vector value Q = 0.35 nm{sup -1}. In the nanocluster model, the casein micelle is considered as a (homogeneous) matrix of caseins in which the colloidal calcium phosphate (CCP

  16. Orthogonally functionalized nanoscale micelles for active targeted codelivery of methotrexate and mitomycin C with synergistic anticancer effect. (United States)

    Li, Yang; Lin, Jinyan; Wu, Hongjie; Chang, Ying; Yuan, Conghui; Liu, Cheng; Wang, Shuang; Hou, Zhenqing; Dai, Lizong


    The design of nanoscale drug delivery systems for the targeted codelivery of multiple therapeutic drugs still remains a formidable challenge (ACS Nano, 2013, 7, 9558-9570; ACS Nano, 2013, 7, 9518-9525). In this article, both mitomycin C (MMC) and methotrexate (MTX) loaded DSPE-PEG micelles (MTX-M-MMC) were prepared by self-assembly using the dialysis technique, in which MMC-soybean phosphatidylcholine complex (drug-phospholipid complex) was encapsulated within MTX-functionalized DSPE-PEG micelles. MTX-M-MMC could coordinate an early phase active targeting effect with a late-phase synergistic anticancer effect and enable a multiple-responsive controlled release of both drugs (MMC was released in a pH-dependent pattern, while MTX was released in a protease-dependent pattern). Furthermore, MTX-M-MMC could codeliver both drugs to significantly enhance the cellular uptake, intracellular delivery, cytotoxicity, and apoptosis in vitro and improve the tumor accumulation and penetration and anticancer effect in vivo compared with either both free drugs treatment or individual free drug treatment. To our knowledge, this work provided the first example of the systemically administrated, orthogonally functionalized, and self-assisted nanoscale micelles for targeted combination cancer chemotherapy. The highly convergent therapeutic strategy opened the door to more simplified, efficient, and flexible nanoscale drug delivery systems.

  17. Health effects of dietary phospholipids

    Directory of Open Access Journals (Sweden)

    Küllenberg Daniela


    Full Text Available Abstract Beneficial effects of dietary phospholipids (PLs have been mentioned since the early 1900's in relation to different illnesses and symptoms, e.g. coronary heart disease, inflammation or cancer. This article gives a summary of the most common therapeutic uses of dietary PLs to provide an overview of their approved and proposed benefits; and to identify further investigational needs. From the majority of the studies it became evident that dietary PLs have a positive impact in several diseases, apparently without severe side effects. Furthermore, they were shown to reduce side effects of some drugs. Both effects can partially be explained by the fact that PL are highly effective in delivering their fatty acid (FA residues for incorporation into the membranes of cells involved in different diseases, e.g. immune or cancer cells. The altered membrane composition is assumed to have effects on the activity of membrane proteins (e.g. receptors by affecting the microstructure of membranes and, therefore, the characteristics of the cellular membrane, e.g. of lipid rafts, or by influencing the biosynthesis of FA derived lipid second messengers. However, since the FAs originally bound to the applied PLs are increased in the cellular membrane after their consumption or supplementation, the FA composition of the PL and thus the type of PL is crucial for its effect. Here, we have reviewed the effects of PL from soy, egg yolk, milk and marine sources. Most studies have been performed in vitro or in animals and only limited evidence is available for the benefit of PL supplementation in humans. More research is needed to understand the impact of PL supplementation and confirm its health benefits.

  18. Nonenzymatic Reactions above Phospholipid Surfaces of Biological Membranes: Reactivity of Phospholipids and Their Oxidation Derivatives. (United States)

    Solís-Calero, Christian; Ortega-Castro, Joaquín; Frau, Juan; Muñoz, Francisco


    Phospholipids play multiple and essential roles in cells, as components of biological membranes. Although phospholipid bilayers provide the supporting matrix and surface for many enzymatic reactions, their inherent reactivity and possible catalytic role have not been highlighted. As other biomolecules, phospholipids are frequent targets of nonenzymatic modifications by reactive substances including oxidants and glycating agents which conduct to the formation of advanced lipoxidation end products (ALEs) and advanced glycation end products (AGEs). There are some theoretical studies about the mechanisms of reactions related to these processes on phosphatidylethanolamine surfaces, which hypothesize that cell membrane phospholipids surface environment could enhance some reactions through a catalyst effect. On the other hand, the phospholipid bilayers are susceptible to oxidative damage by oxidant agents as reactive oxygen species (ROS). Molecular dynamics simulations performed on phospholipid bilayers models, which include modified phospholipids by these reactions and subsequent reactions that conduct to formation of ALEs and AGEs, have revealed changes in the molecular interactions and biophysical properties of these bilayers as consequence of these reactions. Then, more studies are desirable which could correlate the biophysics of modified phospholipids with metabolism in processes such as aging and diseases such as diabetes, atherosclerosis, and Alzheimer's disease.

  19. Quantification of phospholipids classes in human milk. (United States)

    Giuffrida, Francesca; Cruz-Hernandez, Cristina; Flück, Brigitte; Tavazzi, Isabelle; Thakkar, Sagar K; Destaillats, Frédéric; Braun, Marcel


    Phospholipids are integral constituents of the milk fat globule membranes and they play a central role in infants' immune and inflammatory responses. A methodology employing liquid chromatography coupled with evaporative light scattering detector has been optimized and validated to quantify the major phospholipids classes in human milk. Phospholipids were extracted using chloroform and methanol and separated on C18 column. Repeatability, intermediate reproducibility, and recovery values were calculated and a large sample set of human milk analyzed. In human milk, phospholipid classes were quantified at concentrations of 0.6 mg/100 g for phosphatidylinositol; 4.2 mg/100 g for phosphatidylethanolamine, 0.4 mg/100 g for phosphatidylserine, 2.8 mg/100 g for phosphatidylcholine, and 4.6 mg/100 g for sphingomyelin. Their relative standard deviation of repeatability and intermediate reproducibility values ranging between 0.8 and 13.4 % and between 2.4 and 25.7 %, respectively. The recovery values ranged between 67 and 112 %. Finally, the validated method was used to quantify phospholipid classes in human milk collected from 50 volunteers 4 weeks postpartum providing absolute content of these lipids in a relatively large cohort. The average content of total phospholipids was 23.8 mg/100 g that corresponds to an estimated mean intake of 140 mg phospholipids/day in a 4-week old infant when exclusively breast-fed.

  20. Interaction of fluorescent phospholipids with cyclodextrins. (United States)

    Denz, Manuela; Haralampiev, Ivan; Schiller, Sabine; Szente, Lajos; Herrmann, Andreas; Huster, Daniel; Müller, Peter


    Fluorescent analogs of phospholipids are often employed to investigate the structure and dynamics of lipids in membranes. Some of those studies have used cyclodextrins e.g., to modulate the lipid phase. However, the role of the fluorescence moiety of analogs for the interaction between cyclodextrins and fluorescent lipids has not been investigated so far in detail. Therefore, in the present study the interaction of various fluorescent phospholipid analogs with methylated α-, β- and γ- cyclodextrins was investigated. The analogs differed in their structure, in the length of the fatty acyl chain, in the position of the fluorescence group, and in the attached fluorescence moiety (7-nitrobenz-2-oxa-1,3-diazol-4-yl (NBD) or dipyrrometheneboron difluoride (BODIPY)). In aqueous buffer, cyclodextrins bind fluorescent lipids disturbing the organization of the analogs. When incorporated into lipid vesicles, analogs are selectively extracted from the membrane upon addition of cyclodextrins. The results show that the interaction of cyclodextrins with fluorescent phospholipids depends on the cyclodextrin species, the fluorescence moiety and the phospholipid structure. The presented data should be of interest for studies using fluorescent phospholipids and cyclodextrins, since the interaction between the fluorescence group and the cyclodextrin may interfere with the process(es) under study.

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

    Directory of Open Access Journals (Sweden)

    Esmaeil Moazeni


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

  2. Mixed micelle formation with phosphatidylcholines: the influence of surfactants with different molecule structures. (United States)

    Rupp, Christopher; Steckel, Hartwig; Müller, Bernd W


    The number of mixed micellar (MM) drug products being introduced into the commercial pharmaceutical market is very limited although there is need for alternative dosage forms for poorly soluble active drug substances. While known systems are composed of phosphatidylcholine and bile salts, it was the aim of this study to investigate if alternative surfactants are able to form isotropically clear solutions over a broad range of concentrations and at higher ratios of phosphatidylcholine (PC). It was a particular challenge of this work to find a MM system with a unimodal particle size distribution since it is known that surfactants often form vesicles with phospholipids instead of MM. The theoretical approach behind this work was the transfer of the packing parameter concept, which describes the molecular association of one amphiphilic species, to the organisation behaviour of two different amphiphilic species (water-insoluble phospholipid+surfactant leading to MM). Therefore the influence of the surfactant molecular geometry on the ability to form MM with phospholipids was investigated. A homologous series of two different surfactant classes, namely polyglycerol esters and sucrose esters, with a large hydrophilic head region leading to a smaller packing parameter were analysed regarding their ability to form clear MM solutions with PC. For comparison, surfactants with no strictly defined partition between a polar head and a non-polar tail (e.g. Poloxamer 188) were tested. Decaglycerol laurate and especially sucrose laurate (SL) were superior compared to all other tested surfactants with respect to their ability to form clear solutions with hydrogenated PC (hPC) at a higher ratio and over a broad range of concentrations while unsaturated PC showed an inferior performance to form MM. The favourite MM system composed of SL with 0.5 weight fractions of hPC formed about 20 nm sized MM in a concentration range of 1.0-80 mg/mL and showing a unimodal particle size

  3. Thermodynamics and Structural Evolution during a Reversible Vesicle-Micelle Transition of a Vitamin-Derived Bolaamphiphile Induced by Sodium Cholate. (United States)

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


    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.

  4. Hybrid, Nanoscale Phospholipid/Block Copolymer Vesicles

    Directory of Open Access Journals (Sweden)

    Bo Liedberg


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

  5. On the stability and morphology of complex coacervate core micelles: from spherical to wormlike micelles. (United States)

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


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

  6. Chain exchange in triblock copolymer micelles (United States)

    Lu, Jie; Lodge, Timothy; Bates, Frank


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

  7. Tryptophan probes reveal residue-specific phospholipid interactions of apolipoprotein C-III. (United States)

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


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

  8. Structural properties of self-assembled polymeric micelles

    DEFF Research Database (Denmark)

    Mortensen, K.


    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...... for a variety of novel mesophases, including biocontinuous phases and networks of ordered cross-linking micelles. Research has focused on structural studies of block copolymer systems, using small-angle scattering of X-rays and neutrons....

  9. The critical micelle concentration of tetraethylammonium perfluorooctylsulfonate in water. (United States)

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


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

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

    NARCIS (Netherlands)

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


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

  11. Pseudocritical Behavior and Unbinding of Phospholipid Bilayers

    DEFF Research Database (Denmark)

    Lemmich, Jesper; Mortensen, Kell; Ipsen, John Hjorth;


    The temperature dependence of the small-angle neutron scattering from fully hydrated multilamellar phospholipid bilayers near the main phase transition is analyzed by means of a simple geometric model which yields both the lamellar repeat distance as well as the hydrophobic thickness of the bilayer...

  12. Computer simulations of phospholipid - membrane thermodynamic fluctuations

    DEFF Research Database (Denmark)

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


    This paper reports all-atom computer simulations of five phospholipid membranes, DMPC, DPPC, DMPG, DMPS, and DMPSH, with a focus on the thermal equilibrium fluctuations of volume, energy, area, thickness, and order parameter. For the slow fluctuations at constant temperature and pressure (defined...

  13. Separation and identification of phospholipid peroxidation products. (United States)

    Milne, G L; Porter, N A


    The molecular species in mixtures of phospholipid hydroperoxides are difficult to separate and identify by typical chromatographic and mass spectrometric techniques. As reported by Havrilla and coworkers, silver ion coordination ion-spray mass spectrometry (CIS-MS) has proven to be a powerful technique for the identification of mixtures of hydroperoxides. This ionization technique, which involves the formation of Ag+ adducts of the hydroperoxides, provides valuable, unambiguous structural information about the hydroperoxides. Herein, we report a method for the analysis and identification of phospholipid hydroperoxides using CIS-MS. We also report an improved method for the separation of phospholipid hydroperoxides by reversed-phase high-performance liquid chromatography (RP-HPLC), which, for the first time, separates some of the hydroperoxide isomers. CIS-MS can be coupled with this RP-HPLC method by the addition of AgBF4 to the mobile phase or to the HPLC effluent postcolumn, thus allowing powerful HPLC-MS techniques to be used to identify complex mixtures of phospholipid hydroperoxides.

  14. Enthalpy/entropy driven activation of the first interquinone electron transfer in bacterial photosynthetic reaction centers embedded in vesicles of physiologically important phospholipids. (United States)

    Milano, Francesco; Dorogi, Márta; Szebényi, Kornélia; Nagy, László; Maróti, Péter; Váró, György; Giotta, Livia; Agostiano, Angela; Trotta, Massimo


    The thermodynamics and kinetics of light-induced electron transfer in bacterial photosynthetic RCs are sensitive to physiologically important lipids (phosphatidylcholine, cardiolipin and phosphatidylglycerol) in the environment. The analysis of the temperature-dependence of the rate of the P(+)Q(A)(-)Q(B)-->P(+)Q(A)Q(B)(-) interquinone electron transfer revealed high enthalpy change of activation in zwitterionic or neutral micelles and vesicles and low enthalpy change of activation in vesicles constituted of negatively charged phospholipids. The entropy change of activation was compensated by the changes of enthalpy, thus the free energy change of activation ( approximately 500 meV) did not show large variation in vesicles of different lipids.

  15. Modulating alignment of membrane proteins in liquid-crystalline and oriented gel media by changing the size and charge of phospholipid bicelles (United States)

    Lorieau, Justin L; Maltsev, Alexander S.; Louis, John M; Bax, Ad


    We demonstrate that alignment of a structured peptide or small protein solubilized in mixed phospholipid:detergent micelles or bicelles, when embedded in a compressed gel or liquid crystalline medium, can be altered by either changing the phospholipid aggregate shape, charge, or both together. For the hemagglutinin fusion peptide solubilized in bicelles, we show that bicelle shape and charge do not change its helical hairpin structure but impact its alignment relative to the alignment medium, both in charged compressed acrylamide gel and in liquid crystalline d (GpG). The method can be used to generate sets of residual dipolar couplings (RDCs) that correspond to orthogonal alignment tensors, and holds promise for high-resolution structural refinement and dynamic mapping of membrane proteins. PMID:23508769

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

    Energy Technology Data Exchange (ETDEWEB)

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


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

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

    Energy Technology Data Exchange (ETDEWEB)

    Bayraktutan, Tuğba; Meral, Kadem; Onganer, Yavuz, E-mail:


    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.

  18. Synthesis and function of phospholipids in Staphylococcus aureus. (United States)

    Kuhn, Sebastian; Slavetinsky, Christoph J; Peschel, Andreas


    Phospholipids are the major components of bacterial membranes, and changes in phospholipid composition affect important cellular processes such as metabolism, stress response, antimicrobial resistance, and virulence. The most prominent phospholipids in Staphylococcus aureus are phosphatidylglycerol, lysyl-phosphatidylglycerol, and cardiolipin, whose biosynthesis is mediated by a complex protein machinery. Phospholipid composition of the staphylococcal membrane has to be continuously adjusted to changing external conditions, which is achieved by a series of transcriptional and biochemical regulatory mechanisms. This mini-review outlines the current state of knowledge concerning synthesis, regulation, and function of the major staphylococcal phospholipids.

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

    NARCIS (Netherlands)

    Lindhoud, Saskia; Vries, de 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 PAA42PAAm417 and th

  20. 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) an

  1. Lactoferrin binding to transglutaminase cross-linked casein micelles

    NARCIS (Netherlands)

    Anema, S.G.; de Kruif, C.G.


    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

  2. Chirality-mediated polypeptide micelles for regulated drug delivery. (United States)

    Ding, Jianxun; Li, Chen; Zhang, Ying; Xu, Weiguo; Wang, Jincheng; Chen, Xuesi


    Two kinds of triblock poly(ethylene glycol)-polyleucine (PEG-PLeu) copolymers were synthesized through the ring-opening polymerization of L-Leu N-carboxyanhydride (NCA), or equivalent D-Leu NCA and L-Leu NCA with amino-terminated PEG as a macroinitiator. The amphiphilic copolymers spontaneously self-assembled into spherical micellar aggregations in an aqueous environment. The micelle with a racemic polypeptide core exhibited smaller critical micelle concentration and diameter compared to those with a levorotatory polypeptide core. A model anthracycline antineoplastic agent, i.e., doxorubicin (DOX), was loaded into micelles through nanoprecipitation, and the PEG-P(D,L-Leu) micelle exhibited higher drug-loading efficacy than that with a P(L-Leu) core-this difference was attributed to the flexible and compact P(L-Leu) core. Sustained in vitro DOX release from micelles with both levorotatory and racemic polypeptide cores was observed, and the DOX-loaded PEG-P(D,L-Leu) micelle exhibited a slower release rate. More interestingly, DOX-loaded micelles exhibited chirality-mediated antitumor efficacy in vitro and in vivo, which are all better than that of free DOX. Furthermore, both enhanced tumor inhibition and excellent security in vivo were confirmed by histopathological or in situ cell apoptosis analyses. Therefore, DOX-loaded PEG-PLeu micelles appear to be an interesting nanoscale polymeric formulation for promising malignancy chemotherapy.

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

    NARCIS (Netherlands)

    Lindhoud, S.; Vries, de R.J.; Norde, W.; Cohen Stuart, M.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 PAA42PAAm417 and th


    Institute of Scientific and Technical Information of China (English)

    Xiao-chun Qin; Chun-lai Ren


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

  5. Absorption Complex between Porphyrin and Phenothiazine in Reverse Micelles

    Institute of Scientific and Technical Information of China (English)


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

  6. Anthracene functionalized thermosensitive and UV-crosslinkable polymeric micelles

    NARCIS (Netherlands)

    Shi, Yang; Cardoso, Renata M.; Van Nostrum, Cornelus F.; Hennink, Wim E.


    An anthracene-functionalized thermosensitive block copolymer was synthesized, which formed micelles by heating its aqueous solution above the lower critical solution temperature (LCST). The micelles were subsequently crosslinked by UV illumination at 365 nm with a normal handheld UV lamp. The micell

  7. Photoinduced charge separation and enzyme reactions in reversed micelles.

    NARCIS (Netherlands)

    Verhaert, R.M.D.


    In this thesis the performance and coupling of two types of reaction, photoinduced charge separation and enzymatic conversion were studied in reversed micelles. Reversed micelles are 1 to 10 nm sized water droplets dispersed in an organic solution. The dispersant is a detergent (cationogenic, nonion

  8. Magainin II modified polydiacetylene micelles for cancer therapy (United States)

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


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

  9. Polymer Micelles Laden Hydrogel Contact Lenses for Ophthalmic Drug Delivery. (United States)

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


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

  10. Interaction of isopropylthioxanthone with phospholipid liposomes. (United States)

    Momo, Federico; Fabris, Sabrina; Stevanato, Roberto


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

  11. Planar bilayer membranes from photoactivable phospholipids. (United States)

    Borle, F; Sänger, M; Sigrist, H


    Planar bilayer membranes formed from photoactivable phospholipids have been characterized by low frequency voltametry. Cyclic voltametric measurements were applied for simultaneous registration of planar membrane conductivity and capacitance. The procedure has been utilized to characterize the formation and stability of planar bilayer membranes. Bilayer membranes were formed from N'-(1,2-dimyristoyl-sn-glycero-3-phosphoethyl)-N-((m-3- trifluoromethyldiazirine)phenyl)thiourea (C14-PED), a head-group photosensitive phospholipid. In situ photoactivation of C14-PED at wavelengths greater than or equal to 320 nm altered neither the mean conductivity nor the capacitance of the bilayer. Ionophore (valinomycin) and ion channel (gramicidin) activities were not impaired upon photoactivation. In contrast, bilayer membranes formed from 1,2-bis(hexadeca-2,4-dienoyl)-sn- glycero-3-phosphocholine (C16-DENPC) revealed short life times. In situ photopolymerization of the diene fatty acids significantly increased the membrane conductivity or led to membrane rupture.

  12. Therapeutic surfactant-stripped frozen micelles (United States)

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


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

  13. Annexin-Phospholipid Interactions. Functional Implications

    Directory of Open Access Journals (Sweden)

    Javier Turnay


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

  14. Reversible phospholipid nanogels for deoxyribonucleic acid fragment size determinations up to 1500 base pairs and integrated sample stacking. (United States)

    Durney, Brandon C; Bachert, Beth A; Sloane, Hillary S; Lukomski, Slawomir; Landers, James P; Holland, Lisa A


    Phospholipid additives are a cost-effective medium to separate deoxyribonucleic acid (DNA) fragments and possess a thermally-responsive viscosity. This provides a mechanism to easily create and replace a highly viscous nanogel in a narrow bore capillary with only a 10°C change in temperature. Preparations composed of dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and 1,2-dihexanoyl-sn-glycero-3-phosphocholine (DHPC) self-assemble, forming structures such as nanodisks and wormlike micelles. Factors that influence the morphology of a particular DMPC-DHPC preparation include the concentration of lipid in solution, the temperature, and the ratio of DMPC and DHPC. It has previously been established that an aqueous solution containing 10% phospholipid with a ratio of [DMPC]/[DHPC]=2.5 separates DNA fragments with nearly single base resolution for DNA fragments up to 500 base pairs in length, but beyond this size the resolution decreases dramatically. A new DMPC-DHPC medium is developed to effectively separate and size DNA fragments up to 1500 base pairs by decreasing the total lipid concentration to 2.5%. A 2.5% phospholipid nanogel generates a resolution of 1% of the DNA fragment size up to 1500 base pairs. This increase in the upper size limit is accomplished using commercially available phospholipids at an even lower material cost than is achieved with the 10% preparation. The separation additive is used to evaluate size markers ranging between 200 and 1500 base pairs in order to distinguish invasive strains of Streptococcus pyogenes and Aspergillus species by harnessing differences in gene sequences of collagen-like proteins in these organisms. For the first time, a reversible stacking gel is integrated in a capillary sieving separation by utilizing the thermally-responsive viscosity of these self-assembled phospholipid preparations. A discontinuous matrix is created that is composed of a cartridge of highly viscous phospholipid assimilated into a separation matrix

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

    Institute of Scientific and Technical Information of China (English)


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

  16. Ultrasonic transformation of micelle structures: effect of frequency and power. (United States)

    Yusof, Nor Saadah Mohd; Ashokkumar, Muthupandian


    A comprehensive investigation on the effect of ultrasonic frequency and power on the structural transformation of CTABr/NaSal micelles has been carried out. Sonication of this micelle system at various ultrasonic frequencies and power resulted in the formation and separation of two types of micelles. High viscoelastic threadlike micelles of ∼ 2 nm in diameter and several μm in length and tubular micelles possessing a viscosity slightly above that of water with ∼ 30-50 nm diameter and few hundred nm length. The structural transformation of micelles was induced by the shear forces generated during acoustic cavitation. At a fixed acoustic power of 40 W, the structural transformation was found to decrease from 211 to 647 kHz frequency due to the decreasing shear forces generated, as evidenced by rheological measurements and cryo-TEM images. At 355 kHz, an increase in the structural transformation was observed with an increase in acoustic power. These findings provide a knowledge base that could be useful for the manipulation of viscosity of micelles that may have applications in oil industry.

  17. Effect of acute thioacetamide administration on rat brain phospholipid metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Osada, J.; Aylagas, H.; Miro-Obradors, M.J.; Arce, C.; Palacios-Alaiz, E.; Cascales, M. (Tufs Univ., Boston, MA (USA))


    Brain phospholipid composition and the ({sup 32}P)orthophosphate incorporation into brain phospholipids of control and rats treated for 3 days with thioacetamide were studied. Brain phospholipid content, phosphatidylcholine, phosphatidylethanolamine, lysolecithin and phosphatidic acid did not show any significant change by the effect of thioacetamide. In contrast, thioacetamide induced a significant decrease in the levels of phosphatidylserine, sphingomyelin, phosphatidylinositol and diphosphatidylglycerol. After 75 minutes of intraperitoneal label injection, specific radioactivity of all the above phospholipids with the exception of phosphatidylethanolamine and phosphatidylcholine significantly increased. After 13 hours of isotope administration the specific radioactivity of almost all studied phospholipid classes was elevated, except for phosphatidic acid, the specific radioactivity of which did not change and for diphosphatidylglycerol which showed a decrease in specific radioactivity. These results suggest that under thioacetamide treatment brain phospholipids undergo metabolic transformations that may contribute to the hepatic encephalopathy induced by thioacetamide.

  18. NMR solution structure of the peptide fragment 1-30, derived from unprocessed mouse Doppel protein, in DHPC micelles. (United States)

    Papadopoulos, Evangelos; Oglecka, Kamila; Mäler, Lena; Jarvet, Jüri; Wright, Peter E; Dyson, H Jane; Gräslund, Astrid


    The downstream prion-like Doppel (Dpl) protein is a homologue related to the prion protein (PrP). Dpl is expressed in the brains of mice that do not express PrP, and Dpl is known to be toxic to neurons. One mode of toxicity has been suggested to involve direct membrane interactions. PrP under certain conditions of cell trafficking retains an uncleaved signal peptide, which may also hold for the much less studied Dpl. For a peptide with a sequence derived from the N-terminal part (1-30) of mouse Dpl (mDpl(1-30)) CD spectroscopy shows about 40% alpha-helical structure in DHPC and SDS micelles. In aqueous solution it is mostly a random coil. The three-dimensional solution structure was determined by NMR for mDpl(1-30) associated with DHPC micelles. 2D 1H NMR spectra of the peptide in q = 0.25 DMPC/DHPC bicelles only showed signals from the unstructured termini, indicating that the structured part of the peptide resides within the lipid bilayer. Together with 2H2O exchange data in the DHPC micelle solvent, these results show an alpha-helix protected from solvent exchange between residues 7 and 19, and suggest that the alpha-helical segment can adopt a transmembrane localization also in a membrane. Leakage studies with entrapped calcein in large unilamellar phospholipid vesicles showed that the peptide is almost as membrane perturbing as melittin, known to form pores in membranes. The results suggest a possible channel formation mechanism for the unprocessed Dpl protein, which may be related to toxicity through direct cell membrane interaction and damage.

  19. Self-assembly of micelles into designed networks

    Directory of Open Access Journals (Sweden)

    Pyatenko Alexander


    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.

  20. Pressure-induced structural transition of nonionic micelles

    Indian Academy of Sciences (India)

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


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

  1. Effect of compressed CO2 on the critical micelle concentration and aggregation number of AOT reverse micelles in isooctane. (United States)

    Chen, Jing; Zhang, Jianling; Han, Buxing; Feng, Xiaoying; Hou, Minqiang; Li, Wenjing; Zhang, Zhaofu


    The effect of compressed CO2 on the critical micelle concentration (cmc) and aggregation number of sodium bis-2-ethylhexylsulfosuccinate (AOT) reverse micelles in isooctane solution was studied by UV/Vis and fluorescence spectroscopy methods in the temperature range of 303.2-318.2 K and at different pressures or mole fractions of CO2 (X(CO2)). The capacity of the reverse micelles to solubilize water was also determined by direct observation. The standard Gibbs free energy (DeltaGo(m)), standard enthalpy (DeltaHo(m)), and standard entropy (DeltaSo(m)) for the formation of the reverse micelles were calculated by using the cmc data determined. It was discovered that the cmc versus X(CO2) curve and the DeltaGo(m) versus X(CO2) curve for a fixed temperature have a minimum, and the aggregation number and water-solubilization capacity of the reverse micelles reach a maximum at the X(CO2) value corresponding to that minimum. These results indicate that CO2 at a suitable concentration favors the formation of and can stabilize AOT reverse micelles. A detailed thermodynamic study showed that the driving force for the formation of the reverse micelles is entropy.

  2. Huntingtin interactions with membrane phospholipids: strategic targets for therapeutic intervention? (United States)

    Kegel-Gleason, Kimberly B


    The Huntington's disease gene encodes the protein huntingtin (Htt), a soluble protein that largely distributes to the cytoplasm where about half the protein is found in association with membranes. Early studies on Huntington's disease patients suggested changes in membrane phospholipids. Furthermore, changes in phospholipid biosynthetic enzymes have been found in HD cell models using genetic methods. Recent investigations prove that Htt associates with membranes by direct interactions with phospholipids in membranes. Htt contains at least two membrane binding domains, which may work in concert with each other, to target to the appropriate intracellular membranes for diverse functions. Htt has a particular affinity for a specific class of phospholipids called phosphatidylinositol phosphates; individual species of these phospholipids propagate signals promoting cell survival and regulating changes in morphology. Mutant Htt fragments can disrupt synthetic phospholipid bilayers and full-length mutant Htt shows increased binding to numerous phospholipids, supporting the idea that mutant Htt can introduce pathology at the level of phospholipid interactions. There is a great potential to develop therapeutic agents since numerous enzymes regulate the both the biosynthesis/metabolism of lipids and the post-translational modifications of Htt that direct membrane interactions. Understanding the relationship of Htt with membrane phospholipids, and the impact of mutant Htt on membrane-related functions and lipid metabolism, may help identify new modes of therapeutic intervention for Huntington's disease.

  3. 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

  4. 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: [Department of Chemistry, West Bengal State University, Barasat, Kolkata 700126 (India)


    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.

  5. Multicompartmental Microcapsules from Star Copolymer Micelles

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Ikjun; Malak, Sidney T.; Xu, Weinan; Heller, William T.; Tsitsilianis, Constantinos; Tsukruk, Vladimir V.


    We present the layer-by-layer (LbL) assembly of amphiphilic heteroarm pH-sensitive star-shaped polystyrene-poly(2-pyridine) (PSnP2VPn) block copolymers to fabricate porous and multicompartmental microcapsules. Pyridine-containing star molecules forming a hydrophobic core/hydrophilic corona unimolecular micelle in acidic solution (pH 3) were alternately deposited with oppositely charged linear sulfonated polystyrene (PSS), yielding microcapsules with LbL shells containing hydrophobic micelles. The surface morphology and internal nanopore structure of the hollow microcapsules were comparatively investigated for shells formed from star polymers with a different numbers of arms (9 versus 22) and varied shell thickness (5, 8, and 11 bilayers). The successful integration of star unimers into the LbL shells was demonstrated by probing their buildup, surface segregation behavior, and porosity. The larger arm star copolymer (22 arms) with stretched conformation showed a higher increment in shell thickness due to the effective ionic complexation whereas a compact, uniform grainy morphology was observed regardless of the number of deposition cycles and arm numbers. Small-angle neutron scattering (SANS) revealed that microcapsules with hydrophobic domains showed different fractal properties depending upon the number of bilayers with a surface fractal morphology observed for the thinnest shells and a mass fractal morphology for the completed shells formed with the larger number of bilayers. Moreover, SANS provides support for the presence of relatively large pores (about 25 nm across) for the thinnest shells as suggested from permeability experiments. The formation of robust microcapsules with nanoporous shells composed of a hydrophilic polyelectrolyte with a densely packed hydrophobic core based on star amphiphiles represents an intriguing and novel case of compartmentalized microcapsules with an ability to simultaneously store different hydrophilic, charged, and hydrophobic

  6. Drug induced `softening' in phospholipid monolayers (United States)

    Basak, Uttam Kumar; Datta, Alokmay; Bhattacharya, Dhananjay


    Compressibility measurements on Langmuir monolayers of the phospholipid Dimystoryl Phospatidylcholine (DMPC) in pristine form and in the presence of the Non-steroidal Anti-inflammatory Drug (NSAID) Piroxicam at 0.025 drug/lipid (D/L) molecular ratio at different temperatures, show that the monolayer exhibits large increase (and subsequent decrease) in compressibility due to the drug in the vicinity of the Liquid Expanded - Liquid Condensed (LE-LC) phase transition. Molecular dynamics simulations of the lipid monolayer in presence of drug molecules show a disordering of the tail tilt, which is consistent with the above result.

  7. Motional Coherence in Fluid Phospholipid Membranes

    CERN Document Server

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


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

  8. Enantiomer separation by ultrafiltration of enantioselective micelles in multistage systems

    NARCIS (Netherlands)

    Overdevest, P.E.M.


    The Food and Bioprocess Engineering Group of Wageningen University, The Netherlands, is developing a new enantiomer separation system that is based on ultrafiltration (UF) of enantioselective micelles containing chiral selector molecules. Enantiomer molecules are optical isomers (mirror images), and

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

    DEFF Research Database (Denmark)

    Jensen, Andreas Tue Ingemann

    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...... 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...... efficiency was achieved with both chelators (40‐70%). Some of the prepared micelles were found to exhibit gross instabilities, especially with raised temperature, which prevented their in-vivo use. Other micelles were stable and were investigated in xenographted mice. These micelles were 20‐45 nm...

  10. Rheology and phase behavior of dense casein micelle dispersions (United States)

    Bouchoux, A.; Debbou, B.; Gésan-Guiziou, G.; Famelart, M.-H.; Doublier, J.-L.; Cabane, B.


    Casein micelle dispersions have been concentrated through osmotic stress and examined through rheological experiments. In conditions where the casein micelles are separated from each other, i.e., below random-close packing, the dispersions have exactly the flow and dynamic properties of the polydisperse hard-sphere fluid, demonstrating that the micelles interact only through excluded volume effects in this regime. These interactions cause the viscosity and the elastic modulus to increase by three orders of magnitude approaching the concentration of random-close packing estimated at Cmax≈178 g/l. Above Cmax, the dispersions progressively turn into "gels" (i.e., soft solids) as C increases, with elastic moduli G' that are nearly frequency independent. In this second regime, the micelles deform and/or deswell as C increases, and the resistance to deformation results from the formation of bonds between micelles combined with the intrinsic mechanical resistance of the micelles. The variation in G' with C is then very similar to that observed with concentrated emulsions where the resistance to deformation originates from a set of membranes that separate the droplets. As in the case of emulsions, the G' values at high frequency are also nearly identical to the osmotic pressures required to compress the casein dispersions. The rheology of sodium caseinate dispersions in which the caseins are not structured into micelles is also reported. Such dispersions have the behavior of associative polymer solutions at all the concentrations investigated, further confirming the importance of structure in determining the rheological properties of casein micelle systems.

  11. Effects of copolymer component on the properties of phosphorylcholine micelles

    Directory of Open Access Journals (Sweden)

    Wu Z


    Full Text Available Zhengzhong Wu,1 Mengtan Cai,1 Jun Cao,2 Jiaxing Zhang,1 Xianglin Luo1,3 1College of Polymer Science and Engineering, 2National Engineering Research Center for Biomaterials, 3State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu, People’s Republic of China Abstract: Zwitterionic polymers have unique features, such as good compatibility, and show promise in the application of drug delivery. In this study, the zwitterionic copolymers, poly(ε-caprolactone-b-poly(2-methacryloyloxyethyl phosphorylcholine with disulfide (PCL-ss-PMPC or poly(ε-caprolactone-b-poly(2-methacryloyloxyethyl phosphorylcholine or without disulfide (PCL-PMPC and with different block lengths in PCL-ss-PMPC, were designed. The designed copolymers were obtained by a combination of ring-opening polymerization and atom transferring radical polymerization. The crystallization properties of these polymers were investigated. The micelles were prepared based on the obtained copolymers with zwitterionic phosphorylcholine as the hydrophilic shell and PCL as the hydrophobic core. The size distributions of the blank micelles and the doxorubicin (DOX-loaded micelles were uniform, and the micelle diameters were <100 nm. In vitro drug release and intracellular drug release results showed that DOX-loaded PCL-ss-PMPC micelles could release drugs faster responding to the reduction condition and the intracellular microenvironment in contrast to PCL-PMPC micelles. Moreover, in vitro cytotoxicity evaluation revealed that the designed copolymers possessed low cell toxicity, and the inhibiting effect of DOX-loaded phosphorylcholine micelles to tumor cells was related to the components of these copolymers. These results reveal that the reduction-responsive phosphorylcholine micelles with a suitable ratio of hydrophilic/hydrophobic units can serve as promising drug carriers. Keywords: zwitterionic, reduction-sensitive, disulfide, phosphorylcholine

  12. A neutron scattering study of triblock copolymer micelles

    Energy Technology Data Exchange (ETDEWEB)

    Gerstenberg, M.C.


    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

  13. Structure and stability of complex coacervate core micelles with lysozyme. (United States)

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


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

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

    Directory of Open Access Journals (Sweden)

    Conrado Pedebos


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

  15. Phospholipid imprinted polymers as selective endotoxin scavengers (United States)

    Sulc, Robert; Szekely, Gyorgy; Shinde, Sudhirkumar; Wierzbicka, Celina; Vilela, Filipe; Bauer, David; Sellergren, Börje


    Herein we explore phospholipid imprinting as a means to design receptors for complex glycolipids comprising the toxic lipopolysaccharide endotoxin. A series of polymerizable bis-imidazolium and urea hosts were evaluated as cationic and neutral hosts for phosphates and phosphonates, the latter used as mimics of the phospholipid head groups. The bis-imidazolium hosts interacted with the guests in a cooperative manner leading to the presence of tight and well defined 1:2 ternary complexes. Optimized monomer combinations were subsequently used for imprinting of phosphatidic acid as an endotoxin dummy template. Presence of the aforementioned ternary complexes during polymerization resulted in imprinting of lipid dimers – the latter believed to crudely mimic the endotoxin Lipid A motif. The polymers were characterized with respect to template rebinding, binding affinity, capacity and common structural properties, leading to the identification of polymers which were thereafter subjected to an industrially validated endotoxin removal test. Two of the polymers were capable of removing endotoxin down to levels well below the accepted threshold (0.005 EU/mg API) in pharmaceutical production. PMID:28303896

  16. Phospholipid imprinted polymers as selective endotoxin scavengers (United States)

    Sulc, Robert; Szekely, Gyorgy; Shinde, Sudhirkumar; Wierzbicka, Celina; Vilela, Filipe; Bauer, David; Sellergren, Börje


    Herein we explore phospholipid imprinting as a means to design receptors for complex glycolipids comprising the toxic lipopolysaccharide endotoxin. A series of polymerizable bis-imidazolium and urea hosts were evaluated as cationic and neutral hosts for phosphates and phosphonates, the latter used as mimics of the phospholipid head groups. The bis-imidazolium hosts interacted with the guests in a cooperative manner leading to the presence of tight and well defined 1:2 ternary complexes. Optimized monomer combinations were subsequently used for imprinting of phosphatidic acid as an endotoxin dummy template. Presence of the aforementioned ternary complexes during polymerization resulted in imprinting of lipid dimers – the latter believed to crudely mimic the endotoxin Lipid A motif. The polymers were characterized with respect to template rebinding, binding affinity, capacity and common structural properties, leading to the identification of polymers which were thereafter subjected to an industrially validated endotoxin removal test. Two of the polymers were capable of removing endotoxin down to levels well below the accepted threshold (0.005 EU/mg API) in pharmaceutical production.

  17. Depletion of acidic phospholipids influences chromosomal replication in Escherichia coli. (United States)

    Fingland, Nicholas; Flåtten, Ingvild; Downey, Christopher D; Fossum-Raunehaug, Solveig; Skarstad, Kirsten; Crooke, Elliott


    In Escherichia coli, coordinated activation and deactivation of DnaA allows for proper timing of the initiation of chromosomal synthesis at the origin of replication (oriC) and assures initiation occurs once per cell cycle. In vitro, acidic phospholipids reactivate DnaA, and in vivo depletion of acidic phospholipids, results in growth arrest. Growth can be restored by the expression of a mutant form of DnaA, DnaA(L366K), or by oriC-independent DNA synthesis, suggesting acidic phospholipids are required for DnaA- and oriC-dependent replication. We observe here that when acidic phospholipids were depleted, replication was inhibited with a concomitant reduction of chromosomal content and cell mass prior to growth arrest. This global shutdown of biosynthetic activity was independent of the stringent response. Restoration of acidic phospholipid synthesis resulted in a resumption of DNA replication prior to restored growth, indicating a possible cell-cycle-specific growth arrest had occurred with the earlier loss of acidic phospholipids. Flow cytometry, thymidine uptake, and quantitative polymerase chain reaction data suggest that a deficiency in acidic phospholipids prolonged the time required to replicate the chromosome. We also observed that regardless of the cellular content of acidic phospholipids, expression of mutant DnaA(L366K) altered the DNA content-to-cell mass ratio.

  18. Different oxidized phospholipid molecules unequally affect bilayer packing. (United States)

    Megli, Francesco M; Russo, Luciana


    The aim of this study was to gain more detailed knowledge about the effect of the presence of defined oxidized phospholipid molecules in phospholipid bilayers. After chromatographic and mass spectrometry analysis, the previously used product of the Fenton reaction with unsaturated lecithins proved to consist of a plethora of oxidatively modified lecithins, useless either for the detailed study of the effects brought about in the bilayer or as the source of defined oxidized phospholipid molecules. The latter, particularly 2-(omega-carboxyacyl)- and 2-(n-hydroperoxyacyl)-lecithins, can be more conveniently prepared by chemical or enzymatic synthesis rather than by chemical or physical oxidation. The effect of those molecules and of commercially available 12-hydroxy-stearic and dodecanedioic acid was studied in planar supported phospholipid bilayers (SPBs) by use of EPR spectrometry. The SPBs also contained 2-(5-doxylstearoyl)-lecithin as the spin probe, and the EPR spectral anisotropy loss, indicative of bilayer disordering, was measured as a function of the molar percentage of oxidized lipid. Most oxidized lipid molecules examined in this study were able to induce bilayer disordering, while hydroperoxyl group-bearing acyl chains appeared to be much less effective. It is concluded that the effects of different oxidized phospholipids on phospholipid bilayer structure cannot be generalized, as happens with batch-oxidized phospholipids, and that the use of defined oxidized phospholipid molecular species for membrane oxidative stress guarantees a more reliable and detailed response.

  19. Co-assembly of chitosan and phospholipids into hybrid hydrogels

    DEFF Research Database (Denmark)

    Mendes, Ana Carina Loureiro; Shekarforoush, Elhamalsadat; Engwer, Christoph


    Novel hybrid hydrogels were formed by adding chitosan (Ch) to phospholipids (P) self-assembled particles in lactic acid. The effect of the phospholipid concentration on the hydrogel properties was investigated and was observed to affect the rate of hydrogel formation and viscoelastic properties...

  20. Enzyme catalysed production of phospholipids with modified fatty acid profile

    DEFF Research Database (Denmark)

    Vikbjerg, Anders Falk


    Phospholipider har stor anvendelse i levnedsmiddel-, kosmetik-, og farmaceutiske produkter for blandt andet deres emulgerende egenskaber samt evne til at danne liposomer. Interessen for at ændre på phospholipidernes struktur er stigende. Strukturændringer resulterer i ændret funktionalitet. Ved...... projektet var at udvikle processer baseret på enzymatisk interesterificering til produktion af phospholipider med specifik fedtsyre profil (strukturerede phospholipider), og opsætning af membrane separationssystemer til oprensning af strukturerede phospholipider efter reaktion. Produktionen af strukturerede...... phospholipider blev udført i både ”packed bed”- og batchreaktorer med eller uden tilstedeværelse af solvent (organisk opløsningsmiddel). Under den praktiske udførelse af reaktionerne kan dannelsen af biprodukter, grundet sideløbende hydrolyse og acyl migrering, være et alvorligt problem. En grundig belysning af...

  1. Role of phospholipids in endocytosis, phagocytosis, and macropinocytosis. (United States)

    Bohdanowicz, Michal; Grinstein, Sergio


    Endocytosis, phagocytosis, and macropinocytosis are fundamental processes that enable cells to sample their environment, eliminate pathogens and apoptotic bodies, and regulate the expression of surface components. While a great deal of effort has been devoted over many years to understanding the proteins involved in these processes, the important contribution of phospholipids has only recently been appreciated. This review is an attempt to collate and analyze the rapidly emerging evidence documenting the role of phospholipids in clathrin-mediated endocytosis, phagocytosis, and macropinocytosis. A primer on phospholipid biosynthesis, catabolism, subcellular distribution, and transport is presented initially, for reference, together with general considerations of the effects of phospholipids on membrane curvature and charge. This is followed by a detailed analysis of the critical functions of phospholipids in the internalization processes and in the maturation of the resulting vesicles and vacuoles as they progress along the endo-lysosomal pathway.

  2. Micelles and reverse micelles in the nickel bis(2-ethylhexyl) sulfosuccinate/water/isooctane microemulsion. (United States)

    Garza, Cristina; Carbajal-Tinoco, Mauricio D; Castillo, Rolando


    The ternary system Ni(2+)(AOT)(2) (nickel 2-bis[2-ethylhexyl] sulfosuccinate)/water/isooctane presents w/o and o/w microemulsions with a Winsor progression (2Phi-3Phi-2Phi), without the addition of salt; the "fish diagram" was obtained for alpha=0.5 and gamma=0.02-0.22. Using static and dynamic light scattering the micellar size, the ratio of water to surfactant, and the density of micelles for this system were estimated. In addition, the mean interfacial curvature as a function of temperature was obtained.

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

    DEFF Research Database (Denmark)

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


    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...

  4. The impact of phospholipids and phospholipid removal on bioanalytical method performance. (United States)

    Carmical, Jennifer; Brown, Stacy


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

  5. Food enrichment with marine phospholipid emulsions

    DEFF Research Database (Denmark)

    Lu, Henna Fung Sieng; Nielsen, Nina Skall; Baron, Caroline P.

    Many studies have shown that marine phospholipids (PL) provide more advantages than fish oil. They seem to have better bioavailability, better resistance towards oxidation and higher content of eicosapentaenoic acids and docosahexaenoic acids than fish oil, which essentially contains triglycerides...... marine PL emulsions with and without addition of fish oil. The oxidative stability of marine PL emulsions was significantly influenced by the chemical composition of marine PL used for emulsions preparation. For instance, emulsions with good oxidative stability could be obtained when using raw materials...... with high purity, low fish oil content and high PL, cholesterol and α-tocopherol content. In addition, non-enzymatic browning reactions may also affect the oxidative stability of the marine PL emulsion. These reactions included Strecker degradation and pyrrolization, and their occurrence were due...

  6. Packing of ganglioside-phospholipid monolayers

    DEFF Research Database (Denmark)

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


    DPPE monolayer and does not distort the hexagonal in-plane unit cell or out-of-plane two-dimensional (2-D) packing compared with a pure DPPE monolayer. The oligosaccharide headgroups were found to extend normally from the monolayer surface, and the incorporation of these glycolipids into DPPE...... monolayers did not affect hydrocarbon tail packing (fluidization or condensation of the hydrocarbon region). This is in contrast to previous investigations of lipopolymer-lipid mixtures, where the packing structure of phospholipid monolayers was greatly altered by the inclusion of lipids bearing hydrophilic...... polymer groups. Indeed, the lack of packing disruptions by the oligosaccharide groups indicates that protein-GM, interactions, including binding, insertion, chain fluidization, and domain formation (lipid rafts), can be studied in 2-D monolayers using scattering techniques....

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

    Institute of Scientific and Technical Information of China (English)

    XUE Weilan; WANG Dan; ZENG Zuoxiang; GAO Xuechao


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

  8. Stability of complex coacervate core micelles containing metal coordination polymer. (United States)

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


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

  9. A novel temperature-responsive micelle for enhancing combination therapy

    Directory of Open Access Journals (Sweden)

    Peng CL


    Full Text Available Cheng-Liang Peng,1,* Yuan-I Chen,2,3,* Hung-Jen Liu,2 Pei-Chi Lee,2 Tsai-Yueh Luo,1 Ming-Jium Shieh2,3 1Isotope Application Division, Institute of Nuclear Energy Research, Taoyuan, 2Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, 3Department of Oncology, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan *These authors contributed equally to this work Abstract: A novel thermosensitive polymer p(N-isopropylacrylamide-co-poly[ethylene glycol] methyl ether acrylate-block-poly(epsilon-caprolactone, p(NIPAAM-co-PEGMEA-b-PCL, was synthesized and developed as nanomicelles. The hydrophobic heat shock protein 90 inhibitor 17-allylamino-17-demethoxygeldanamycin and the photosensitizer cyanine dye infrared-780 were loaded into the core of the micelles to achieve both chemotherapy and photothermal therapy simultaneously at the tumor site. The release of the drug could be controlled by varying the temperature due to the thermosensitive nature of the micelles. The micelles were less than 200 nm in size, and the drug encapsulation efficiency was >50%. The critical micelle concentrations were small enough to allow micelle stability upon dilution. Data from cell viability and animal experiments indicate that this combination treatment using photothermal therapy with chemotherapy had synergistic effects while decreasing side effects. Keywords: thermosensitive, photothermal therapy, chemotherapy, nanocarrier, control release, synergistic effect

  10. Applications of polymeric micelles with tumor targeted in chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Ding Hui; Wang Xiaojun; Zhang Song; Liu Xinli, E-mail: [Shandong Polytechnic University, Shandong Provincial Key Laboratory of Microbial Engineering (China)


    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 {approx} 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.

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

    Directory of Open Access Journals (Sweden)

    Kang SangHwa


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

  12. Phospholipid remodeling and eicosanoid signaling in colon cancer cells. (United States)

    Das, Siddhartha; Martinez, Leobarda Robles; Ray, Suparna


    Phospholipid remodeling and eicosanoid synthesis are central to lipid-based inflammatory reactions. Studies have revealed that membrane phospholipid remodeling by fatty acids through deacylation/reacylation reactions increases the risk of colorectal cancers (CRC) by allowing the cells to produce excess inflammatory eicosanoids, such as prostaglandins, thromboxanes and leukotrienes. Over the years, efforts have been made to understand the lipid remodeling pathways and to design anti-cancer drugs targeting the enzymes of eicosanoid biosynthesis. Here, we discuss the recent progress in phospholipid remodeling and eicosanoid biosynthesis in CRC.

  13. Biomimetic oral mucin from polymer micelle networks (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

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

    DEFF Research Database (Denmark)

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


    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)...

  15. Casein micelles: size distribution in milks from individual cows. (United States)

    de Kruif, C G Kees; Huppertz, Thom


    The size distribution and protein composition of casein micelles in the milk of Holstein-Friesian cows was determined as a function of stage and number of lactations. Protein composition did not vary significantly between the milks of different cows or as a function of lactation stage. Differences in the size and polydispersity of the casein micelles were observed between the milks of different cows, but not as a function of stage of milking or stage of lactation and not even over successive lactations periods. Modal radii varied from 55 to 70 nm, whereas hydrodynamic radii at a scattering angle of 73° (Q² = 350 μm⁻²) varied from 77 to 115 nm and polydispersity varied from 0.27 to 0.41, in a log-normal distribution. Casein micelle size in the milks of individual cows was not correlated with age, milk production, or lactation stage of the cows or fat or protein content of the milk.

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

    KAUST Repository

    Deng, Lin


    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.

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

    KAUST Repository

    Nunes, Suzana Pereira


    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. From micelle supramolecular assemblies in selective solvents to isoporous membranes. (United States)

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


    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.

  19. Multicompartment Micelles From π-Shaped ABC Block Copolymers

    Institute of Scientific and Technical Information of China (English)

    XIA Jun; ZHONG Chong-Li


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

  20. Artificial Self-Sufficient P450 in Reversed Micelles

    Directory of Open Access Journals (Sweden)

    Teruyuki Nagamune


    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.

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

    Poša, Mihalj; Tepavčević, Vesna


    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.

  2. Controlled mixing of lanthanide(III) ions in coacervate core micelles. (United States)

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


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


    Institute of Scientific and Technical Information of China (English)

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


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

  4. Shell and core cross-linked poly(L-lysine)/poly(acrylic acid) complex micelles. (United States)

    Hsieh, Yi-Hsuan; Hsiao, Yung-Tse; Jan, Jeng-Shiung


    We report the versatility of polyion complex (PIC) micelles for the preparation of shell and core cross-linked (SCL and CCL) micelles with their surface properties determined by the constituent polymer composition and cross-linking agent. The negatively and positively charged PIC micelles with their molecular structure and properties depending on the mixing weight percentage and polymer molecular weight were first prepared by mixing the negatively and positively charged polyions, poly(acrylic acid) (PAA) and poly(L-lysine) (PLL). The feasibility of preparing SCL micelles was demonstrated by cross-linking the shell of the negatively and positively charged micelles using cystamine and genipin, respectively. The core of the micelles can be cross-linked by silica deposition to stabilize the assemblies. The shell and/or core cross-linked micelles exhibited excellent colloid stability upon changing solution pH. The drug release from the drug-loaded SCL micelles revealed that the controllable permeability of the SCL micelles can be achieved by tuning the cross-linking degree and the SCL micelles exhibited noticeable pH-responsive behavior with accelerated release under acidic conditions. With the versatility of cross-linking strategies, it is possible to prepare a variety of SCL and CCL micelles from PIC micelles.

  5. Curcumin and Osteosarcoma: Can Invertible Polymeric Micelles Help?

    Directory of Open Access Journals (Sweden)

    Avudaiappan Maran


    Full Text Available Systematic review of experimental and clinical data on the use of curcumin in the treatment of osteosarcoma is presented. The current status of curcumin’s therapeutic potential against bone cancer is analyzed in regard to using polymeric micelles (including recently developed invertible, responsive, micelles as a platform for curcumin delivery to treat osteosarcoma. The potential of micellar assemblies from responsive macromolecules in a controlled delivery of curcumin to osteosarcoma cells, and the release using a new inversion mechanism is revealed.

  6. Folding of DsbB in mixed micelles

    DEFF Research Database (Denmark)

    Otzen, Daniel


    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...... data are always open to alternative interpretations, time-resolved studies in mixed micelles provide a useful approach to measure membrane protein stability over a wide range of concentrations of SDS and DM, as well as a framework for the future characterization of the DsbB folding mechanism....

  7. Herpes simplex virus 1 induces de novo phospholipid synthesis

    Energy Technology Data Exchange (ETDEWEB)

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


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

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

    DEFF Research Database (Denmark)

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


    Phospholipid bilayers represent a complex, anisotropic environment fundamentally different from bulk oil or octanol, for instance. Even "simple" drug association to phospholipid bilayers can only be fully understood if the slab-of-hydrocarbon approach is abandoned and the complex, anisotropic pro...... of these interactions in PLD in particular. We also focus on a potential causal connection between drug-induced PLD and steatohepatitis, which is induced by some cationic amphiphilic drugs....

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

    DEFF Research Database (Denmark)

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


    Chitosan (Ch) polysaccharide was mixed with phospholipids (P) to generate electrospun hybrid nanofibers intended to be used as platforms for transdermal drug delivery. Ch/P nanofibers exibithed average diameters ranging from 248 +/- 94 nm to 600 +/- 201 nm, depending on the amount of phospholipid...... culture plate (control). The release of curcumin, diclofenac and vitamin B12, as model drugs, from Ch/P hybrid nanofibers was investigated, demonstrating their potential utilization as a transdermal drug delivery system....

  10. Enhancement by cytidine of membrane phospholipid synthesis (United States)

    G-Coviella, I. L.; Wurtman, R. J.


    Cytidine, as cytidine 5'-diphosphate choline, is a major precursor in the synthesis of phosphatidylcholine in cell membranes. In the present study, we examined the relationships between extracellular levels of cytidine, the conversion of [14C]choline to [14C]phosphatidylcholine, and the net syntheses of phosphatidylcholine and phosphatidylethanolamine by PC12 cells. The rate at which cytidine (as [3H]cytidine) was incorporated into the PC12 cells followed normal Michaelis-Menten kinetics (Km = 5 microM; Vmax = 12 x 10(-3) mmol/mg of protein/min) when the cytidine concentrations in the medium were below 50 microM; at higher concentrations, intracellular [3H]cytidine nucleotide levels increased linearly. Once inside the cell, cytidine was converted mainly into cytidine triphosphate. In pulse-chase experiments, addition of cytidine to the medium caused a time- and dose-dependent increase (by up to 30%) in the incorporation of [14C]choline into membrane [14C]-phosphatidylcholine. When the PC12 cells were supplemented with both cytidine and choline for 14 h, small but significant elevations (p less than 0.05) were observed in their absolute contents of membrane phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine, all increasing by 10-15% relative to their levels in cells incubated with choline alone. Exogenous cytidine, acting via cytidine triphosphate, can thus affect the synthesis and levels of cell membrane phospholipids.

  11. Molecular Insights into Phospholipid -- NSAID Interactions (United States)

    Babu Boggara, Mohan; Krishnamoorti, Ramanan


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

  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: [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: [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: [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


    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. Biomimetic surface modification of polyurethane with phospholipids grafted carbon nanotubes. (United States)

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


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

  14. Phospholipid Synthesis in Sindbis Virus-Infected Cells (United States)

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


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

  15. 胶束及反胶束微环境中的槲皮素金属配合物%Study on Quercetin-Metal Complexes in Micelle Solutions and Reversed Micellar Systems

    Institute of Scientific and Technical Information of China (English)

    李方; 张进; 张新申; 李波


    The critical micelle concentrations (cmc) of surfactants in the Quercetin-metal coordination complex solutions have been determined by using the method of conductance ratio. In Quercetin coordination complex solution there were two cmc values at the lower concentration area of CTAB [C16H33N(CH3)3Br]. And this phenomenon about two cmc points was much similar to that of natural bio-surfactant. All the CTAB, SDBS (C12H25C6H4SO3Na) and Tween-80 could improve the water-solubility of Quercetin coordination complexes when the concentrations of these suffactants were above the cmc values, but only CTAB increased the oil-solubility of these complexes. Therefore, Quercetin-metal-CTAB micelle congeries could go into the octanol phase through oil-water interface. In phospholipid reversed micellar system, the transfer efficiency of complex between the two phases was influenced by pH of the water phase, and around pH 7 the complexes were easy to enter the phospholipid-octanol phase.

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

    DEFF Research Database (Denmark)

    Ek, Pramod Kumar

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

  17. Nanoparticle self-assembly in mixtures of phospholipids with styrene/maleic acid copolymers or fluorinated surfactants (United States)

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


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

  18. Biochemical characterization of GM1 micelles-Amphotericin B interaction. (United States)

    Leonhard, Victoria; Alasino, Roxana V; Bianco, Ismael D; Garro, Ariel G; Heredia, Valeria; Beltramo, Dante M


    In this work a thorough characterization of the GM1 micelle-Amphotericin B (AmB) interaction was performed. The micelle formation as well as the drug loading occurs spontaneously, although influenced by the physicochemical conditions, pH and temperature. The chromatographic profile of GM1-AmB complexes at different molar ratios shows the existence of two populations. The differential absorbance of GM1, monomeric and aggregate AmB, allowed us to discriminate the presence of all of them in both fractions. Thus, we noted that at higher proportion of AmB in the complex, increases the larger population which is composed mainly of aggregated AmB. The physical behavior of these micelles shows that both GM1- AmB complexes were stable in solution for at least 30 days. However upon freeze-thawing or lyophilization-solubilization cycles, only the smallest population, enriched in monomeric AmB, showed a complete solubilization. In vitro, GM1-AmB micelles were significantly less toxic on cultured cells than other commercial micellar formulations as Fungizone, but had a similar behavior to liposomal formulations as Ambisome. Regarding the antifungal activity of the new formulation, it was very similar to that of other formulations. The characterization of these GM1-AmB complexes is discussed as a potential new formulation able to improve the antifungal therapeutic efficiency of AmB.

  19. Casein Micelles: Size Distribution in Milks from Individual Cows

    NARCIS (Netherlands)

    de Kruif, C.G.; Huppertz, T.


    The size distribution and protein composition of casein micelles in the milk of Holstein-Friesian cows was determined as a function of stage and number of lactations. Protein composition did not vary significantly between the milks of different cows or as a function of lactation stage. Differences i

  20. Extraction of L-Aspartic Acid with Reverse Micelle System

    Directory of Open Access Journals (Sweden)

    Özlem AYDOĞAN


    Full Text Available The aim of this study is to investigate the extraction L-aspartic acid which is a hydrophobic amino acid with reverse micelle system. Production of amino acids by fermentation has been more important in recent years. These amino acids are obtained in dilute aqueous solutions and have to be separated from excess substrate, inorganic salts and by-products. Recently, separation of amino acids from fermentation media by reverse micelle extraction has received a great deal of attention. In this study, reverse micelle phase includes aliquat-336 as a surfactant, 1-decanol as a co-surfactant and isooctane as an apolar solvent. Experiments were performed at 150 rpm stirring rate, at 30 oC, for 30 min extraction time with equal volumes of reverse micelle and aqueous phases. Concentration of L-aspartic acid was analyzed by liquid chromatography (HPLC. The extraction yield increased with increasing pH and aliquat-336 concentration and with decreasing initial amino acid concentration. Maximum ekstraction yield (68 % was obtained at pH of 12, surfactant concentration of 200 mM and an initial amino acid concentration of 5 mM.

  1. Complex coacervate core micelles from iron-based coordination polymers. (United States)

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


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

  2. Molecular dynamics simulation of a polysorbate 80 micelle in water

    NARCIS (Netherlands)

    Amani, Amir; York, Peter; de Waard, Hans; Anwar, Jamshed


    The structure and dynamics of a single molecule of the nonionic surfactant polysorbate 80 (POE (20) sorbitan monooleate; Tween 80 (R)) as well as a micelle comprising sixty molecules of polysorbate 80 in water have been investigated by molecular dynamics simulation. In its free state in water the po

  3. Fluorescence dynamics of green fluorescent protein in AOT reversed micelles

    NARCIS (Netherlands)

    Uskova, M.A.; Borst, J.W.; Hink, M.A.; Hoek, van A.; Schots, A.; Klyachko, N.L.; Visser, A.J.W.G.


    We have used the enhanced green fluorescent protein (EGFP) to investigate the properties of surfactant-entrapped water pools in organic solvents (reversed micelles) with steady-state and time-resolved fluorescence methods. The surfactant used was sodium bis(2-ethylhexyl)sulfosuccinate (AOT) and the

  4. Dynamics of Chain Exchange in Block Copolymer Micelles (United States)

    Lodge, Timothy

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

  5. In vivo toxicity of cationic micelles and liposomes

    DEFF Research Database (Denmark)

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


    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 last...

  6. Polymeric micelles in anticancer therapy : Targeting, imaging and triggered release

    NARCIS (Netherlands)

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


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

  7. Structure and flexibility of worm-like micelles

    DEFF Research Database (Denmark)

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


    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...

  8. Complement monitoring of Pluronic 127 gel and micelles

    DEFF Research Database (Denmark)

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


    transformations from gel to the solution state further incite complement through calcium-sensitive pathways, where a role for C1q and antibodies has been eliminated. Poloxamer addition to plasma/serum (at levels above its critical micelle concentration, cmc) induced formation of large and diffused structures...

  9. Biodegradable polymeric micelle-encapsulated doxorubicin suppresses tumor metastasis by killing circulating tumor cells (United States)

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


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

  10. Thermodynamics of micelle formation in a water-alcohol solution of sodium tetradecyl sulfate (United States)

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


    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.

  11. Targeted therapy of colorectal neoplasia with rapamycin in peptide-labeled pegylated octadecyl lithocholate micelles. (United States)

    Khondee, Supang; Rabinsky, Emily F; Owens, Scott R; Joshi, Bishnu P; Qiu, Zhen; Duan, Xiyu; Zhao, Lili; Wang, Thomas D


    Many powerful drugs have limited clinical utility because of poor water solubility and high systemic toxicity. Here, we formulated a targeted nanomedicine, rapamycin encapsulated in pegylated octadecyl lithocholate micelles labeled with a new ligand for colorectal neoplasia, LTTHYKL peptide. CPC;Apc mice that spontaneously develop colonic adenomas were treated with free rapamycin, plain rapamycin micelles, and peptide-labeled rapamycin micelles via intraperitoneal injection for 35days. Endoscopy was performed to monitor adenoma regression in vivo. We observed complete adenoma regression at the end of therapy. The mean regression rate for peptide-labeled rapamycin micelles was significantly greater than that for plain rapamycin micelles, Prapamycin micelles compared to that of free drug, and no other toxicities were found on chemistries. Together, this unique targeted micelle represents a potential therapeutic for colorectal neoplasia with comparable therapeutic efficacy to rapamycin free drug and significantly less systemic toxicity.

  12. Reverse micelles as suitable microreactor for increased biohydrogen production

    Energy Technology Data Exchange (ETDEWEB)

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


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

  13. Digestion of phospholipids after secretion of bile into the duodenum changes the phase behavior of bile components. (United States)

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


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

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

    Directory of Open Access Journals (Sweden)

    Peh KK


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

  15. Equation of State for Phospholipid Self-Assembly

    DEFF Research Database (Denmark)

    Marsh, Derek


    of transfer converge at ∼-18°C. An equation of state for the free energy of self-assembly formulated from this thermodynamic data depends on the heat capacity of transfer as the sole parameter needed to specify a particular lipid. For lipids lacking calorimetric data, measurement of the critical micelle...

  16. Erythrocyte phospholipid and polyunsaturated fatty acid composition in diabetic retinopathy.

    Directory of Open Access Journals (Sweden)

    Philippe Koehrer

    Full Text Available Long chain polyunsaturated fatty acids (LCPUFAs including docosahexaenoic acid and arachidonic acid are suspected to play a key role in the pathogenesis of diabetes. LCPUFAs are known to be preferentially concentrated in specific phospholipids termed as plasmalogens. This study was aimed to highlight potential changes in the metabolism of phospholipids, and particularly plasmalogens, and LCPUFAs at various stages of diabetic retinopathy in humans.We performed lipidomic analyses on red blood cell membranes from controls and mainly type 2 diabetes mellitus patients with or without retinopathy. The fatty acid composition of erythrocytes was determined by gas chromatography and the phospholipid structure was determined by liquid chromatography equipped with an electrospray ionisation source and coupled with a tandem mass spectrometer (LC-ESI-MS/MS. A significant decrease in levels of docosahexaenoic acid and arachidonic acid in erythrocytes of diabetic patients with or without retinopathy was observed. The origin of this decrease was a loss of phosphatidyl-ethanolamine phospholipids esterified with these LCPUFAs. In diabetic patients without retinopathy, this change was balanced by an increase in the levels of several phosphatidyl-choline species. No influence of diabetes nor of diabetic retinopathy was observed on the concentrations of plasmalogen-type phospholipids.Diabetes and diabetic retinopathy were associated with a reduction of erythrocyte LCPUFAs in phosphatidyl-ethanolamines. The increase of the amounts of phosphatidyl-choline species in erythrocytes of diabetic patients without diabetic retinopathy might be a compensatory mechanism for the loss of LC-PUFA-rich phosphatidyl-ethanolamines.

  17. Decrease in membrane phospholipid unsaturation induces unfolded protein response. (United States)

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


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

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

    Energy Technology Data Exchange (ETDEWEB)

    Ingemann Jensen, A.T.


    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

  19. Calculations of critical micelle concentration by dissipative particle dynamics simulations: the role of chain rigidity. (United States)

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


    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.

  20. Effects of architecture on the stability of thermosensitive unimolecular micelles. (United States)

    Steinschulte, Alexander A; Schulte, Bjoern; Rütten, Stephan; Eckert, Thomas; Okuda, Jun; Möller, Martin; Schneider, Stefanie; Borisov, Oleg V; Plamper, Felix A


    The influence of architecture on polymer interactions is investigated and differences between branched and linear copolymers are found. A comprehensive picture is drawn with the help of a fluorescence approach (using pyrene and 4HP as probe molecules) together with IR or NMR spectroscopy and X-ray/light scattering measurements. Five key aspects are addressed: (1) synergistic intramolecular complexation within miktoarm stars. The proximity of thermoresponsive poly(propylene oxide) (PPO) and poly(dimethylaminoethyl methacrylate) (PDMAEMA) within a miktoarm star leads to complexation between these weakly interacting partners. Consequently, the original properties of the constituents are lost, showing hydrophobic domains even at low temperatures, at which all homopolymers are water soluble. (2) Unimolecular micelles for miktoarm stars. The star does not exhibit intermolecular self-assembly in a large temperature range, showing unimers up to 55 °C. This behavior was traced back to a reduced interfacial tension between the PPO-PDMAEMA complex and water (PDMAEMA acts as a "microsurfactant"). (3) Unimolecular to multimolecular micelle transition for stars. The otherwise stable unimolecular micelles self-assemble above 55 °C. This aggregation is not driven by PPO segregation, but by collapse of residual PDMAEMA. This leads to micrometer-sized multilamellar vesicles stabilized by poly(ethylene oxide) (PEO). (4) Prevention of pronounced complexation within diblock copolymers. In contrast to the star copolymers, PPO and PDMAEMA adapt rather their homopolymer behavior within the diblock copolymers. Then they show their immanent LCST properties, as PDMAEMA turns insoluble at elevated temperatures, whereas PPO becomes hydrophobic below room temperature. (5) Two-step micellization for diblock copolymers. Upon heating of linear copolymers, the dehydration of PPO is followed by self-assembly into spherical micelles. An intermediate prevalence of unimolecular micelles is revealed

  1. Possible mechanism of adhesion in a mica supported phospholipid bilayer

    Energy Technology Data Exchange (ETDEWEB)

    Pertsin, Alexander, E-mail: [Angewandte Physikalische Chemie, Universität Heidelberg, Im Neuenheimer Feld 253, 69120 Heidelberg (Germany); Institute of Organo-Element Compounds, Russian Academy of Sciences, Vavilov Str. 28, 117991 Moscow (Russian Federation); Grunze, Michael [Angewandte Physikalische Chemie, Universität Heidelberg, Im Neuenheimer Feld 253, 69120 Heidelberg (Germany); Institute for Functional Interfaces, Karlsruhe Institute of Technology, Hermann-von- Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen (Germany)


    Phospholipid bilayers supported on hydrophilic solids like silica and mica play a substantial role in fundamental studies and technological applications of phospholipid membranes. In both cases the molecular mechanism of adhesion between the bilayer and the support is of primary interest. Since the possibilities of experimental methods in this specific area are rather limited, the methods of computer simulation acquire great importance. In this paper we use the grand canonical Monte Carlo technique and an atomistic force field to simulate the behavior of a mica supported phospholipid bilayer in pure water as a function of the distance between the bilayer and the support. The simulation reveals a possible adhesion mechanism, where the adhesion is due to individual lipid molecules that protrude from the bilayer and form widely spaced links with the support. Simultaneously, the bilayer remains separated from the bilayer by a thin water interlayer which maintains the bilayer fluidity.

  2. Training affects muscle phospholipid fatty acid composition in humans

    DEFF Research Database (Denmark)

    Helge, Jørn Wulff; Wu, B J; Willer, Mette;


    on the muscle membrane phospholipid fatty acid composition in humans. Seven male subjects performed endurance training of the knee extensors of one leg for 4 wk. The other leg served as a control. Before, after 4 days, and after 4 wk, muscle biopsies were obtained from the vastus lateralis. After 4 wk......, the phospholipid fatty acid contents of oleic acid 18:1(n-9) and docosahexaenoic acid 22:6(n-3) were significantly higher in the trained (10.9 +/- 0.5% and 3.2 +/- 0.4% of total fatty acids, respectively) than the untrained leg (8.8 +/- 0.5% and 2.6 +/- 0.4%, P ... a minimal role, as the influence of dietary intake is similar on both legs. Regular exercise training per se influences the phospholipid fatty acid composition of muscle membranes but has no effect on the composition of fatty acids stored in triacylglycerols within the muscle....

  3. Neutron diffraction studies of amphipathic helices in phospholipid bilayers

    Energy Technology Data Exchange (ETDEWEB)

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


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

  4. [Tracheal phospholipid composition and respiratory distress syndrome of the newborn]. (United States)

    Obladen, M


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

  5. Ligand binding characteristics and aggregation behavior of purified cow's milk folate binding protein depends on the presence of amphiphatic substances including cholesterol, phospholipids, and synthetic detergents. (United States)

    Holm, Jan; Hansen, Steen Ingemann


    Folate binding protein was purified from cow's milk by a combination of cation exchange chromatography and methotrexate-AH-sepharose affinity chromatography. Dilution of the preparation to concentrations of protein less than 10 nM resulted in drastic changes of radioligand (folate) binding characteristics, i.e., a decrease in binding affinity with a change from upward to downward convex Scatchard plots and increased ligand dissociation combined with appearance of weak-affinity aggregated forms of the binding protein on gel filtration. These findings, consistent with a model predicting dimerization between unliganded and liganded monomers, were reversed in the presence of material eluted from the affinity column after adsorption of the protein(cofactor) or cholesterol, phospholipids, and synthetic detergents. The latter amphiphatic substances form micelles and lipid bilayers which could separate hydrophobic unliganded monomers from hydrophilic liganded monomers in the surrounding aqueous medium and thereby prevent association between these monomeric forms prevailing at low concentrations of the protein. Our data have some bearings on studies which show that cholesterol and phospholipids are necessary for the clustering of folate receptors in the cell membrane; a process required for optimum receptor function and internalization of folate.

  6. Fat lowers fat: purified phospholipids as emerging therapies for dyslipidemia. (United States)

    Sahebkar, Amirhossein


    Dyslipidemia is a major coronary heart disease (CHD) risk factor. In spite of the proven efficacy of statin drugs in reducing CHD burden, there is still much room for the discovery of novel therapeutic agents to address the considerable residual cardiovascular risk that remains after treatment with currently available medications. In particular, there is an urgent demand for drugs capable of boosting the concentration and/or function of high-density lipoprotein (HDL) and apolipoprotein A-I (apo A-I), thereby promoting reverse cholesterol transport. Phospholipids are naturally occurring fats that play indispensible role in human health via their structural, energy storage, signal transduction and metabolic functions. Supplementation with either purified or mixed preparations of bioactive phospholipids has been reported to ameliorate a range of nutritional and cardiovascular disorders. Moreover, several lines of evidence have supported the efficacy of dietary phospholipids in reducing serum and hepatic contents of cholesterol and triglycerides, while increasing HDL-C and apo A-I levels. These beneficial effects of phospholipids could be attributed to their ability in reducing intestinal cholesterol absorption, enhancing biliary cholesterol excretion and modulating the expression and activity of transcriptional factors and enzymes that are involved in lipoprotein metabolism. Given their extreme safety and biocompatibility, dietary supplementation with phospholipid preparations, in particular phosphatidylinositol, appears as a novel and effective strategy that could be used as an alternative or adjunctive therapy to the current medications. The present review outlines the in-vitro, in-vivo and clinical findings on the anti-dyslipidemic effects of three most abundant phospholipids in the human body and diet namely phosphatidylcholine, phosphatidylethanolamine and phosphatidylinositol.

  7. NMR analyses of deuterated phospholipids isolated from Pichia angusta (United States)

    Massou, S.; Augé, S.; Tropis, M.; Lindley, N. D.; Milon, A.


    The phospholipid composition of methylotrophic yeasts grown on deuterated and hydrogenated media has been determined by proton and phosphorus NMR. By using a line narrowing solvent, we could obtain linewidth lower than 2 Hz, and all the resonances could be resolved. Phospholipids were identified on the basis of their chemical shift and by 31P - H correlations (HMQC - HOHAHA gradient enhanced experiments). We have thus analysed qualitatively and quantitatively lipids mixtures directly after chloroform-methanol extraction. The lipid composition is deeply modified after growth in deuterated medium were phosphatidyl Inositol (PI) becomes the major lipid, instead of a PC, PS, PI mixture in hydrogenated conditions. La composition en phospholipides de levures méthylotrophes ayant poussé sur des milieux de cultures hydrogénés et deutériés a été déterminée par RMN du proton et du phosphore31. L'utilisation d'un solvant d'affinement a permis d'obtenir des largeurs de raies inférieures à 2Hz et de résoudre toutes les classes de phospholipides. Ils sont ensuite identifiés par leur déplacement chimique et par des corrélations phosphore - proton spécifiques (expériences HMQC-HOHAHA gradients). Cette approche a permis une analyse qualitative et quantitative de mélanges de phospholipides directement après extraction au chloroforme-méthanol. La composition en phospholipides est profondément modifiée lors de la croissance en milieu perdeutérié où l'on observe un lipide majoritaire, le phosphatidyl Inositol (PI), au lieu d'un mélange PC, PS PI en milieu hydrogéné.

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

    Directory of Open Access Journals (Sweden)

    Matthew eGumbleton


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

  9. Regulation of inositol phospholipid binding and signaling through syndecan-4

    DEFF Research Database (Denmark)

    Couchman, John R; Vogt, Susan; Lim, Ssang-Taek;


    inositol phospholipids. In turn, lipid binding stabilizes the syndecan in oligomeric form, with subsequent binding and activation of protein kinase C. The specificity of phospholipid binding and its potential regulation are investigated here. Highest affinity of the syndecan-4 cytoplasmic domain was seen...... examined. Inositol hexakisphosphate, but not inositol tetrakisphosphate, also had high affinity for the syndecan-4 cytoplasmic domain and could compete effectively with PtdIns(4,5)P(2). Since inositol hexaphosphate binding to syndecan-4 does not promote oligomer formation, it is a potential down...

  10. Genetic Analysis of Digestive Physiology Using Fluorescent Phospholipid Reporters (United States)

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


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

  11. Large magnetic anisotropy in ferrihydrite nanoparticles synthesized from reverse micelles

    Energy Technology Data Exchange (ETDEWEB)

    Duarte, E L [Instituto de Fisica, Universidade de Sao Paulo, CP 66318, Sao Paulo, 05315-970 (Brazil); Itri, R [Instituto de Fisica, Universidade de Sao Paulo, CP 66318, Sao Paulo, 05315-970 (Brazil); Jr, E Lima [Instituto de Fisica, Universidade de Sao Paulo, CP 66318, Sao Paulo, 05315-970 (Brazil); Baptista, M S [Instituto de Quimica, Universidade de Sao Paulo, Avenida Professor Lineu Prestes 748, Sao Paulo (Brazil); Berquo, T S [Institute for Rock Magnetism, University of Minnesota, 100 Union Street SE, Minneapolis, MN 55455-0128 (United States); Goya, G F [Instituto de Nanociencias de Aragon (INA), Universidad de Zaragoza, Pedro Cerbuna 12 (50009), Zaragoza (Spain)


    Six-line ferrihydrite (FH) nanoparticles have been synthesized in the core of reverse micelles, used as nanoreactors to obtain average particle sizes {approx} 2-4 nm. The blocking temperatures T{sub B}{sup m} extracted from magnetization data increased from {approx}10 to 20 K for increasing particle size. Low-temperature Moessbauer measurements allowed us to observe the onset of differentiated contributions from the particle core and surface as the particle size increases. The magnetic properties measured in the liquid state of the original emulsion showed that the ferrihydrite phase is not present in the liquid precursor, but precipitates in the micelle cores after the free water is freeze-dried. Systematic susceptibility {chi}{sub ac}(f,T) measurements showed the dependence of the effective magnetic anisotropy energies E{sub a} with particle volume, and yielded an effective anisotropy value of K{sub eff} = 312 {+-} 10 kJ m{sup -3}.

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

    DEFF Research Database (Denmark)

    Andersen, Simon Ivar; Christensen, S. D.


    of asphaltenes obtained by solvent extraction with toluene/heptane mixtures. These subfractions get more complex in structure as the toluene content of the extraction solvent increases and at the same time the CMC of the asphaltenes in pure toluene decreases. There is an indication that the presence of "lower......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...

  13. Estimation of interfacial acidity of sodium dodecyl sulfate micelles

    Indian Academy of Sciences (India)

    Arghya Dey; G Naresh Patwari


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

  14. Formation of wormlike micelles in anionic surfactant AES aqueous solutions

    Institute of Scientific and Technical Information of China (English)


    The growth and structure of anionic micelles of sodium dodecyl trioxyethylene sulfate (AES) in the presence 3+of multivalent counterion Al were investigated by means of dynamic rheological methods. It has been obtained by the measurements of shear viscosity, complex viscosity and dynamic moduli, as well as the application of Cox-Merz rule and Cole-Cole plot that wormlike micelle and network structure could be formed in AES/AlCl3 aqueous solutions.The structure was of a character of nonlinear viscoelastic fluid and departure from the simple Maxwell model. The technique of freeze-fracture transmission electron microscopy (FF-TEM) was also used to confirm the formation of this interesting structure.``

  15. Biosensors with reversed micelle-enzyme sensitive membrane

    Institute of Scientific and Technical Information of China (English)


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

  16. Development of the simple and sensitive method for lipoxygenase assay in AOT/isooctane reversed micelles. (United States)

    Park, Kyung Min; Kim, Yu Na; Choi, Seung Jun; Chang, Pahn-Shick


    In this study, we investigated the possibility of reversed micelles, widely used as an enzyme reactor for lipases, for the determination of lipoxygenase activity. Although it is rapid and simple, reversed micelles have some limitations, such as interference by UV-absorbing materials and surfactant. Lipoxygenase activity in the reversed micelles was determined by reading the absorbance of the lipid hydroperoxidation product (conjugated diene) at 234 nm. Among surfactants and organic media, AOT and isooctane were most effective for the dioxygenation of linoleic acid in reversed micelles. The strong absorbance of AOT in the UV region is a major obstacle for the direct application of the AOT/isooctane reversed micelles to lipoxygenase activity determination. To prevent interference by AOT, we added an AOT removal step in the procedure for lipoxygenase activity determination in reversed micelles. The lipoxygenase activity was dependent on water content, and maximum activity was obtained at an R-value of 10.

  17. Gold-Loaded Polymeric Micelles with Temperature-Modulated Catalytic Activity

    Institute of Scientific and Technical Information of China (English)

    HU Na; SHI Dongjian; LI Jihang; LI Junfeng; CHEN Mingqing


    Four-armed amphiphilic block copolymers, polystyrene-b-poly(N-isopropylacrylamide) (PS-b-PNIPAM)4, were synthesized by atom transfer radical polymerization (ATRP). (PS-b-PNIPAM)4 self-assembled into micelles with PS block as core and thermoresponsive PNIPAM block as corona. The gold nanoparticles (Au NPs) with average diameter about 5.8 nm were immobilized on the surfaces of the micelles by the reduction of the corresponding ions. The micelle-supported gold nanoparticles (Au-micelles) were applied to catalyze the reduction ofp-nitrophenol. Moreover, the activity of the Au-micelle catalyst could be modulated by the temperature and the Au-micelles could be easily recovered by changing the temperature and recycled four times with high catalytic activity.

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

    Institute of Scientific and Technical Information of China (English)

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


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

  19. Biosynthetic labeling and two-color imaging of phospholipids in cells. (United States)

    Jao, Cindy Y; Roth, Mary; Welti, Ruth; Salic, Adrian


    Phospholipids with a choline head group are abundant components of all biological membranes, performing critical functions in cellular structure, metabolism, and signaling. In spite of their importance, our ability to visualize choline phospholipids in vivo remains very limited. We present a simple and robust chemical strategy to image choline phospholipids, based on the metabolic incorporation of azidocholine analogues, that accurately reflects the normal biosynthetic incorporation of choline into cellular phospholipids. Azidocholine-labeled phospholipids can be imaged in cells with high sensitivity and resolution, following derivatization with fluorophores, by bio-orthogonal chemical reactions compatible with live-cell imaging. We used this method to visualize the subcellular localization of choline phospholipids. We also demonstrate that double metabolic labeling with azidocholine and propargylcholine allows sensitive two-color imaging of choline phospholipids. Our method represents a powerful approach to directly image phospholipids, and to study their dynamics in cells and tissues.

  20. Nature of the charged headgroup determines the fusogenic potential and membrane properties of lithocholic acid phospholipids. (United States)

    Bhargava, Priyanshu; Singh, Manish; Sreekanth, Vedagopuram; Bajaj, Avinash


    Phospholipids play a crucial role in many cellular processes ranging from selective membrane permeability, to membrane fission and fusion, to cellular signaling. Headgroups of phospholipids determine the membrane properties and fusogenicity of these lipids with target cell membranes. We studied the fusogenic and membrane properties of phospholipids possessing unnatural charged headgroups with model membranes using laurdan based membrane hydration studies, DPH based membrane fluidity, and differential scanning calorimetry. We unravel that fusogenicity, membrane hydration, and fluidity of membranes are strongly contingent on the nature of the phospholipid charged headgroup. Our studies unraveled that introduction of bulky headgroups like dimethylamino pyridine induces maximum membrane hydration and perturbations with high fusogenicity as compared to small headgroup based phospholipids. These phospholipids also have the capability of high retention in DPPC membranes. Hydration and fluidity of these phospholipid-doped DPPC membranes are contingent on the nature of the charged headgroup. This study would help in future design of phospholipid based nanomaterials for effective drug delivery.

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

    NARCIS (Netherlands)

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


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

  2. Chain exchange kinetics of block copolymer micelles in ionic liquids (United States)

    Ma, Yuanchi; Lodge, Timothy

    The chain exchange kinetics of block copolymer micelles has been studied using time-resolved small-angle neutron scattering (TR-SANS), a key tool in determining the average micelle composition in contrast-matched solvents. In this work, PMMA-block-PnBMA was selected as the model block copolymer, which has a LCST behavior in the common ionic liquids, [EMIM][TFSI] and [BMIM][TFSI]. We examined the chain exchange kinetics of three PMMA-block-PnBMA copolymers, with identical PMMA block length (MPMMA = 25000) and different PnBMA block lengths (MPnBMA = 24000, 35000 and 53000); the Flory-Huggins interaction parameter (χ) between the core (PnBMA) and the solvent were varied by mixing [EMIM][TFSI] and [BMIM][TFSI] in different ratios. We found that the relaxation of the initial segregation of h- and d- micelles followed the same form with the time as previously developed by our group. Assuming that single chain expulsion is the rate limiting step, the thermal barrier was found to depend linearly on the core block length (Ncore) . Furthermore, the effect of χ on the chain exchange kinetics will also be discussed.

  3. Enhancing oral bioavailability of quercetin using novel soluplus polymeric micelles (United States)

    Dian, Linghui; Yu, Enjiang; Chen, Xiaona; Wen, Xinguo; Zhang, Zhengzan; Qin, Lingzhen; Wang, Qingqing; Li, Ge; Wu, Chuanbin


    To improve its poor aqueous solubility and stability, the potential chemotherapeutic drug quercetin was encapsulated in soluplus polymeric micelles by a modified film dispersion method. With the encapsulation efficiency over 90%, the quercetin-loaded polymeric micelles (Qu-PMs) with drug loading of 6.7% had a narrow size distribution around mean size of 79.00 ± 2.24 nm, suggesting the complete dispersibility of quercetin in water. X-ray diffraction (XRD) patterns illustrated that quercetin was in amorphous or molecular form within PMs. Fourier transform infrared spectroscopy (FTIR) indicated that quercetin formed intermolecular hydrogen bonding with carriers. An in vitro dialysis test showed the Qu-PMs possessed significant sustained-release property, and the formulation was stable for at least 6 months under accelerated conditions. The pharmacokinetic study in beagle dogs showed that absorption of quercetin after oral administration of Qu-PMs was improved significantly, with a half-life 2.19-fold longer and a relative oral bioavailability of 286% as compared to free quercetin. Therefore, these novel soluplus polymeric micelles can be applied to encapsulate various poorly water-soluble drugs towards a development of more applicable therapeutic formulations.

  4. Polymeric micelles encapsulating photosensitizer: structure/photodynamic therapy efficiency relation. (United States)

    Gibot, Laure; Lemelle, Arnaud; Till, Ugo; Moukarzel, Béatrice; Mingotaud, Anne-Françoise; Pimienta, Véronique; Saint-Aguet, Pascale; Rols, Marie-Pierre; Gaucher, Mireille; Violleau, Frédéric; Chassenieux, Christophe; Vicendo, Patricia


    Various polymeric micelles were formed from amphiphilic block copolymers, namely, poly(ethyleneoxide-b-ε-caprolactone), poly(ethyleneoxide-b-d,l-lactide), and poly(ethyleneoxide-b-styrene). The micelles were characterized by static and dynamic light scattering, electron microscopy, and asymmetrical flow field-flow fractionation. They all displayed a similar size close to 20 nm. The influence of the chemical structure of the block copolymers on the stability upon dilution of the polymeric micelles was investigated to assess their relevance as carriers for nanomedicine. In the same manner, the stability upon aging was assessed by FRET experiments under various experimental conditions (alone or in the presence of blood proteins). In all cases, a good stability over 48 h for all systems was encountered, with PDLLA copolymer-based systems being the first to release their load slowly. The cytotoxicity and photocytotoxicity of the carriers were examined with or without their load. Lastly, the photodynamic activity was assessed in the presence of pheophorbide a as photosensitizer on 2D and 3D tumor cell culture models, which revealed activity differences between the 2D and 3D systems.

  5. Hydrotropy: monomer-micelle equilibrium and minimum hydrotrope concentration. (United States)

    Shimizu, Seishi; Matubayasi, Nobuyuki


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

  6. 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)


    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.

  7. How to Squeeze a Sponge: Casein Micelles under Osmotic Stress, a SAXS Study


    Bouchoux, Antoine; Gésan-Guiziou, Geneviève; Pérez, Javier; Cabane, Bernard


    By combining the osmotic stress technique with small-angle x-ray scattering measurements, we followed the structural response of the casein micelle to an overall increase in concentration. When the aqueous phase that separates the micelles is extracted, they behave as polydisperse repelling spheres and their internal structure is not affected. When they are compressed, the micelles lose water and shrink to a smaller volume. Our results indicate that this compression is nonaffine, i.e., some p...

  8. Structure of phosphate fluorosurfactant based reverse micelles in supercritical carbon dioxide


    Senapati, S; Keiper, J. S.; de Simone, J. M.; Wignall, G. D.; Melnichenko, Y. B.; Frielinghaus, H; Berkowitz, M. L.


    The existence of microemulsions in the system composed of phosphate-based fluorosurfactant, water, and supercritical CO2 is demonstrated by small-angle neutron scattering experiments. A computer simulation study performed on a reverse micelle created in this system shows that the micelle remains stable over a 4 ns time period of the simulation. While the data obtained from the experiments provide information about the size of the reverse micelle, the data obtained from the simulations provide...

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

    Institute of Scientific and Technical Information of China (English)

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


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

  10. Effect of Micelle Composition on Acidic Drugs Separation Behavior by Micellar Electrokinetic Capillary Chromatography

    Institute of Scientific and Technical Information of China (English)


    Micellar electrokinetic capillary chromatography (MECC) separation of four acidic drugs similar in structure was studied. Both anionic surfactant sodium dodecyl sulfate (SDS) and nonionic surfactant Tween 20 were used to form single micelles and mixed micelles as pseudostationary phases. The effects of the composition of micellar solution on retention behaviors were studied. The results indicate that there is markedly different selectivity among SDS, Tween 20 and the mixed micelles systems.

  11. Combined effect of sesamin and soybean phospholipid on hepatic fatty acid metabolism in rats


    Ide, Takashi


    We studied the combined effect of sesamin (1:1 mixture of sesamin and episesamine) and soybean phospholipid on lipid metabolism in rats. Male rats were fed diets supplemented with 0 or 2 g/kg sesamin, and containing 0 or 50 g/kg soybean phospholipid, for 19 days. Sesamin and soybean phospholipid decreased serum triacylglycerol concentrations and the combination of these compounds further decreased the parameter in an additive fashion. Soybean phospholipid but not sesamin reduced the hepatic c...

  12. 一种独特的仿生磷脂--Phospholipid(R)CDM%Unique biomimetic phospholipid complex--Phospholipid (R) CDM

    Institute of Scientific and Technical Information of China (English)




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

    KAUST Repository

    Shi, Yifeng


    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.

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

  15. Polymer micelles for delayed release of therapeutics from drug-releasing surfaces with nanotubular structures. (United States)

    Sinn Aw, Moom; Addai-Mensah, Jonas; Losic, Dusan


    A new approach to engineer a local drug delivery system with delayed release using nanostructured surface with nanotube arrays is presented. TNT arrays electrochemically generated on a titanium surface are used as a model substrate. Polymer micelles as drug carriers encapsulated with drug are loaded at the bottom of the TNT structure and their delayed release is obtained by loading blank micelles (without drug) on the top. The delayed and time-controlled drug release is successfully demonstrated by controlling the ratio of blank and drug loaded-micelles. The concept is verified using four different polymer micelles (regular and inverted) loaded with water-insoluble (indomethacin) and water-soluble drugs (gentamicin).

  16. Atomistic Simulation of Solubilization of Polycyclic Aromatic Hydrocarbons in a Sodium Dodecyl Sulfate Micelle. (United States)

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


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

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

    Energy Technology Data Exchange (ETDEWEB)

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


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

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

    Institute of Scientific and Technical Information of China (English)

    方波; 曹丹红; 江体乾


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


    Institute of Scientific and Technical Information of China (English)

    Chen Guo; Hao Wen; Huizhou Liu


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

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


    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.

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

    Institute of Scientific and Technical Information of China (English)


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

  2. 21 CFR 862.1575 - Phospholipid test system. (United States)


    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Phospholipid test system. 862.1575 Section 862.1575 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... treatment of disorders involving lipid (fat) metabolism. (b) Classification. Class I (general controls)....

  3. Mechanisms of anti-phospholipid antibody formation and action

    NARCIS (Netherlands)

    de Groot, Philip G.


    The antiphospholipid syndrome is an autoimmune disease characterised by the clinical features of recurrent thrombosis in the venous or arterial circulation and foetal losses in combination with circulating anti-phospholipid antibodies in the blood of the afflicted patients. Over the last 25 years nu


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

  5. Phospholipid signaling responses in salt-stressed rice leaves

    NARCIS (Netherlands)

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


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

  6. Membrane Phospholipid Redistribution in Cytokinesis: A Theoretical Model

    Institute of Scientific and Technical Information of China (English)

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


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

  7. Phospholipid organization in monkey erythrocytes upon Plasmodium knowlesi infection

    NARCIS (Netherlands)

    Schaft, P.H. van der; Beaumelle, B.; Vial, H.; Roelofsen, B.; Kamp, J.A.F. op den; Deenen, L.L.M. van


    The phospholipid organization in monkey erythrocytes upon Plasmodium knowlesi infection has been studied. Parasitized and nonparasitized erythrocytes from malaria-infected blood were separated and pure erythrocyte membranes from parasitized cells were isolated using Affi-Gel beads. In this way, the

  8. Characterization of associated proteins and phospholipids in natural rubber latex. (United States)

    Sansatsadeekul, Jitlada; Sakdapipanich, Jitladda; Rojruthai, Porntip


    Non-rubber components present in natural rubber (NR) latex, such as proteins and phospholipids, are presumed to be distributed in the serum fraction as well as surrounding the rubber particle surface. The phospholipid-protein layers covering the rubber particle surface are especially interesting due to their ability to enhance the colloidal stability of NR latex. In this study, we have characterized the components surrounding the NR particle surface and investigated their role in the colloidal stability of NR particles. Proteins from the cream fraction were proteolytically removed from the NR latex and compare to those from the serum fractions using SDS-polyacrylamide gel electrophoresis revealing that both fractions contained similar proteins in certain molecular weights such as 14.5, 25 and 27 kDa. Phospholipids removed from latex by treatment with NaOH were analyzed using (1)H-NMR spectroscopy and several major signals were assignable to -(CH(2))(n)-, -CH(2)OP, -CH(2)OC═O and -OCH(2)CH(2)NH-. These signals are important evidence that indicates phospholipids associate with the rubber chain. The colloidal behavior of rubber lattices before and after removal of protein-lipid membrane was evaluated by zeta potential analysis and scanning electron microscope (SEM). The lowest zeta potential value of NR particles was observed at pH 10, consequently leading to the highest stability of rubber particles. Additionally, SEM micrographs clearly displayed a gray ring near the particle surface corresponding to the protein-lipid membrane layer.

  9. Dynamic phospholipid signaling by G protein-coupled receptors

    NARCIS (Netherlands)

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


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

  10. Prostaglandin phospholipid conjugates with unusual biophysical and cytotoxic properties

    DEFF Research Database (Denmark)

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


    The synthesis of two secretory phospholipase A(2) IIA sensitive 15-deoxy-Delta(12,14)-prostaglandin J(2) phospholipid conjugates is described and their biophysical and biological properties are reported. The conjugates spontaneously form particles in the liposome size region upon dispersion in an...

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

    Directory of Open Access Journals (Sweden)

    Ming-Fa Hsieh


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

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

    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: [Department of Biomedical Engineering, Chung Yuan Christian University, 200, Chung Pei Rd., Chung Li, Taiwan (China)


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

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

    CERN Document Server

    Peterlin, Primoz; Diamant, Haim; Haleva, Emir


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

  14. Block copolymer micelles as nanocontainers for controlled release of proteins from biocompatible oil phases. (United States)

    Miller, Andrew C; Bershteyn, Anna; Tan, Wuisiew; Hammond, Paula T; Cohen, Robert E; Irvine, Darrell J


    Biocompatible oils are used in a variety of medical applications ranging from vaccine adjuvants to vehicles for oral drug delivery. To enable such nonpolar organic phases to serve as reservoirs for delivery of hydrophilic compounds, we explored the ability of block copolymer micelles in organic solvents to sequester proteins for sustained release across an oil-water interface. Self-assembly of the block copolymer, poly(-caprolactone)-block-poly(2-vinyl pyridine) (PCL-b-P2VP), was investigated in toluene and oleic acid, a biocompatible naturally occurring fatty acid. Micelle formation in toluene was characterized by dynamic light scattering (DLS) and atomic force microscopy (AFM) imaging of micelles cast onto silicon substrates. Cryogenic transmission electron microscopy confirmed a spherical morphology in oleic acid. Studies of homopolymer solubility implied that micelles in oleic acid consist of a P2VP corona and a PCL core, while P2VP formed the core of micelles assembled in toluene. The loading of two model proteins (ovalbumin (ova) and bovine serum albumin (BSA)) into micelles was demonstrated with loadings as high as 7.8% wt of protein per wt of P2VP in oleic acid. Characterization of block copolymer morphology in the two solvents after protein loading revealed spherical particles with similar size distributions to the as-assembled micelles. Release of ova from micelles in oleic acid was sustained for 12-30 h upon placing the oil phase in contact with an aqueous bath. Unique to the situation of micelle assembly in an oily phase, the data suggest protein is sequestered in the P2VP corona block of PCL-b-P2VP micelles in oleic acid. More conventionally, protein loading occurs in the P2VP core of micelles assembled in toluene.

  15. Development, Characterization, and Evaluation of PSMA-Targeted Glycol Chitosan Micelles for Prostate Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Jing Xu


    Full Text Available Prostate cancer-binding peptides- (PCP- modified polymeric micelles were prepared and used for the treatment of prostate-specific membrane antigen- (PSMA- expressing prostate cancer in a target-specific manner. Cholesterol-modified glycol chitosan (CHGC was synthesized. PCP-conjugated CHGC (PCP-CHGC micelles were fabricated and characterized. The degree of substitution was 5.2 PCP groups and 5.8 cholesterol groups per 100 sugar residues of glycol chitosan. The critical aggregation concentration (CAC of PCP-CHGC copolymer was 0.0254 mg/mL. Doxorubicin (DOX was chosen as a model antitumor drug. The DOX-loaded micelles were prepared by an o/w method. The mean diameter of DOX-loaded PCP-CHGC (DOX-PCP-CHGC micelles was 293 nm determined by dynamic light scattering (DLS. DOX released from drug-loaded micelles was in a biphasic manner. DOX-PCP-CHGC micelles exhibited higher cytotoxicity in vitro against PSMA-expressing LNCaP cells than DOX-loaded CHGC (DOX-CHGC micelles. Moreover, the cellular uptake of DOX-PCP-CHGC micelles determined by confocal laser scanning microscopy (CLSM and flow cytometry was higher than that of DOX-CHGC micelles in LNCaP cells. Importantly, DOX-PCP-CHGC micelles demonstrated stronger antitumor efficacy against LNCaP tumor xenograft models than doxorubicin hydrochloride and DOX-CHGC micelles. Taken together, this study provides a potential way in developing PSMA-targeted drug delivery system for prostate cancer therapy.

  16. Bioactive oxidatively truncated phospholipids in inflammation and apoptosis: formation, targets, and inactivation. (United States)

    McIntyre, Thomas M


    This report reviews structurally related phospholipid oxidation products that are biologically active where molecular mechanisms have been defined. Phospholipids containing polyunsaturated fatty acyl residues are chemically or enzymatically oxidized to phospholipid hydroperoxides, which may fragment on either side of the newly introduced peroxy function to form phospholipids with a truncated sn-2 residue. These truncated phospholipids not subject to biologic control of their production and, depending on the sn-2 residue length and structure, can stimulate the plasma membrane receptor for PAF. Alternatively, these chemically formed products can be internalized by a transport system to either stimulate the lipid activated nuclear transcription factor PPARγ or at higher levels interact with mitochondria to initiate the intrinsic apoptotic cascade. Intracellular PAF acetylhydrolases specifically hydrolyze truncated phospholipids, and not undamaged, biosynthetic phospholipids, to protect cells from oxidative death. Truncated phospholipids are also formed within cells where they couple cytokine stimulation to mitochondrial damage and apoptosis. The relevance of intracellular truncated phospholipids is shown by the complete protection from cytokine induced apoptosis by PAF acetylhydrolase expression. This protection shows truncated phospholipids are the actual effectors of cytokine mediated toxicity. This article is part of a Special Issue entitled: Oxidized phospholipids-their properties and interactions with proteins.

  17. Unimolecular micelles and electrostatic nanoassemblies stemming from hyperbranched polyethyleneimine

    Energy Technology Data Exchange (ETDEWEB)

    Picco, A.; Azzaroni, O.; Ceolin, M. [Instituto de Investigaciones Fisicoquimicas Teoricas y Aplic, La Plata, BA (Argentina); Silbestri, G.F. [Universidad Nacional del Sur, Bahia Blanca Bueno (Argentina)


    Full text: Hyperbranched polyethyleneimine (HPEI) was used as a building block to construct different self-assembled soft nanomaterials. This was accomplished via covalent linkage of carboxylic acids (CA) of different chain lengths to terminal amino groups of HPEI, thus leading to the formation of reverse unimolecular micelles constituted of a hydrophilic core and a hydrophobic shell. On the other hand, acid base interactions in organic solvents between CAs and peripheral amino groups of HPEI also facilitated the formation of electrostatic assemblies with reverse micellar properties. In this work we describe the formation of both structures as well as their characterization using diverse techniques including SAXS, NMR, IR, and fluorescence spectroscopy, among others. Unimolecular micelles were synthesized through the reaction of HPEI (Mn= 10 KDa) and acyl chlorides with different chain lengths (C8, C10, C12, C14, C16, C18). Depending on the chain length, the solvent and the temperature, a broad variety of supra macromolecular assemblies can be observed by SAXS measurements, including structured aggregation, and gelation. Hyperbranched electrostatic assemblies were simply produced by mixing HPEI with selected carboxylic acids (C8, C10, C12, C14, C16, C18) in an appropriate solvent, which dissolves the CA, or both reactants, i.e. chloroform, toluene or THF. The formation of the assemblies was corroborated using FT-IR by monitoring the appearance of the carboxylate bands. SAXS experiments of electrostatically assembled micelles showed globular, core-shell structures, whose characteristics are similar, in many cases, to their covalent counterparts prepared using the same chain length CA shells. (author)

  18. Molecular dynamics simulations of helical antimicrobial peptides in SDS micelles: what do point mutations achieve?

    DEFF Research Database (Denmark)

    Khandelia, Himanshu; Kaznessis, Yiannis N


    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 mic...

  19. Separation of racemic mixture by ultrafiltration of enantioselective micelles. 2 (De) complexation kinetics

    NARCIS (Netherlands)

    Overdevest, P.E.M.; Schutyser, M.A.I.; Bruin, de T.J.M.; Riet, van 't K.; Keurentjes, J.T.F.; Padt, van der A.


    The application of enantioselective micelles in ultrafiltration systems can be an alternative route to meet the increasing demand for enantiopure products. We have studied the separation of D,L-phenylalanine (Phe) by cholesteryl-L-glutamate:CuII (CLG:CuII) anchored in nonionic micelles (intrinsic en

  20. The association of low-molecular-weight hydrophobic compounds with native casein micelles in bovine milk. (United States)

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


    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.

  1. Improving anticancer activity and reducing systemic toxicity of doxorubicin by self-assembled polymeric micelles (United States)

    Gou, MaLing; Shi, HuaShan; Guo, Gang; Men, Ke; Zhang, Juan; Zheng, Lan; Li, ZhiYong; Luo, Feng; Qian, ZhiYong; Zhao, Xia; Wei, YuQuan


    In an attempt to improve anticancer activity and reduce systemic toxicity of doxorubicin (Dox), we encapsulated Dox in monomethoxy poly(ethylene glycol)-poly(ɛ-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.

  2. Green synthetic, multifunctional hybrid micelles with shell embedded magnetic nanoparticles for theranostic applications. (United States)

    Li, Yongyong; Ma, Junping; Zhu, Haiyan; Gao, Xiaolong; Dong, Haiqing; Shi, Donglu


    The objective of this study is to design and develop a green-synthetic, multifunctional hybrid micelles with shell embedded magnetic nanoparticles for theranostic applications. The hybrid micelles were engineered based on complex micelles self-assembled from amphiphilic block copolymers Pluronic F127 and peptide-amphiphile (PA) pal-AAAAHHHD. The reason to choose PA is due to its amphiphilic character and the coordination capability for Fe(3+) and Fe(2+). The PA incorporation allows the in situ growth of the magnetic iron oxide nanoparticles onto the complex micelles, to yield the nanostructures with shell embedded magnetic nanoparticles at an ambient condition without any organic solvents. The anticancer drug doxorubicin (DOX) can be efficiently loaded into the hybrid micelles. Interestingly, the magnetic nanoparticles anchored on the shell were found to significantly retard the DOX release behavior of the drug loaded hybrid micelles. It was proposed that a cross-linking effect of the shell by magnetic nanoparticles is a key to underlie the above intriguing phenomenon, which could enhance the stability and control the drug diffusion of the hybrid micelles. Importantly, in vitro and in vivo magnetic resonance imaging (MRI) revealed the potential of these hybrid micelles to be served as a T2-weighted MR imaging contrast enhancer for clinical diagnosis.

  3. 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


    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

  4. Delivery of the photosensitizer Pc 4 in PEG-PCL micelles for in vitro PDT studies. (United States)

    Master, Alyssa M; Rodriguez, Myriam E; Kenney, Malcolm E; Oleinick, Nancy L; Gupta, Anirban Sen


    The silicon phthalocyanine Pc 4 is a second-generation photosensitizer that has several properties superior to other photosensitizers currently approved by the FDA, and it has shown significant promise for photodynamic therapy (PDT) in several cancer cells in vitro and model tumor systems in vivo. However, because of the high hydrophobicity of Pc 4, its formulation for in vivo delivery and favorable biodistribution become challenging. To this end, we are studying encapsulation and delivery of Pc 4 in block copolymer micelles. Here, we report the development of biocompatible PEG-PCL micelle nanoparticles, encapsulation of Pc 4 within the micelle core by hydrophobic association with the PCL block, and in vitro PDT studies of the micelle-formulated Pc 4 in MCF-7c3 human breast cancer cells. Our studies demonstrate efficient encapsulation of Pc 4 in the micelles, intracellular uptake of the micelle-formulated Pc 4 in cells, and significant cytotoxic effect of the formulation upon photoirradiation. Quantitative estimation of the extent of Pc 4 loading in the micelles and the photocytotoxicity of the micelle-incorporated Pc 4 demonstrate the promise of our approach to develop a biocompatible nanomedicine platform for tumor-targeted delivery of Pc 4 for site-selective PDT.

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

    DEFF Research Database (Denmark)

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


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

  6. Comprehensive theory for star-like polymer micelles: combining classical nucleation and polymer brush theory

    NARCIS (Netherlands)

    Sprakel, J.H.B.; Leermakers, F.A.M.; Cohen Stuart, M.A.; Besseling, N.A.M.


    A comprehensive theory is proposed that combines classical nucleation and polymer brush theory to describe star-like polymer micelles. With a minimum of adjustable parameters, the model predicts properties such as critical micelle concentrations and micellar size distributions. The validity of the p

  7. 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: [West China Second University Hospital, West China Women' s and Children' s Hospital, Sichuan University, Chengdu 610041 (China)


    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.

  8. Deoxycholic acid-grafted PEGylated chitosan micelles for the delivery of mitomycin C. (United States)

    Zhang, Xiu-Rong; Shi, Nian-Qiu; Zhao, Yang; Zhu, He-Yun; Guan, Jiao; Jin, Ying


    Mitomycin C (MTC) was incorporated to a micelle system preparing from a polymer named deoxycholic acid chitosan-grafted poly(ethylene glycol) methyl ether (mPEG-CS-DA). mPEG-CS-DA was synthesized and characterized by (1)H nuclear magnetic resonance ((1)H-NMR) and Fourier transform infrared spectroscopy. mPEG-CS-DA formed a core-shell micellar structure with a critical micelle concentration of 6.57 µg/mL. The mPEG-CS-DA micelles were spherical with a hydrodynamic diameter of about 231 nm. After poly(ethylene glycol)ylation of deoxycholic acid chitosan (CS-DA), the encapsulation efficiency and drug loading efficiency increased from 50.62% to 56.42% and from 20.51% to 24.13%, respectively. The mPEG-CS-DA micelles possessed a higher drug release rate than the CS-DA micelles. For pharmacokinetics, the area under the curve (AUC) of the mPEG-CS-DA micelles was 1.5 times higher than that of MTC injection, and these micelles can enhance the bioavailability of MTC. mPEG-CS-DA micelles reduced the distribution of MTC in almost all normal tissues and had the potential to improve the kidney toxicity caused by MTC injection.

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

    Directory of Open Access Journals (Sweden)

    Li Xinru


    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.

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

    Institute of Scientific and Technical Information of China (English)

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


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

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

    Energy Technology Data Exchange (ETDEWEB)

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


    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.

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

    NARCIS (Netherlands)

    Rijcken, C.J.F.


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

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

    Institute of Scientific and Technical Information of China (English)


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

  14. Histological study on side effects and tumor targeting of a block copolymer micelle on rats. (United States)

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


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

  15. Shaping and patterning gold nanoparticles via micelle templated photochemistry (United States)

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


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

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

    DEFF Research Database (Denmark)

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


    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......, suggesting significant differences in their composition or structure. Detailed size histograms of CMs during aggregation also revealed the presence of two distinct subpopulations with different growth amplitudes and kinetics. The dependence of these distinct nanoscale processes/parameters on aggregation...

  17. Mechano-responsive hydrogels crosslinked by reactive block copolymer micelles (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

  18. 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.


    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 ther

  19. Effective repair of traumatically injured spinal cord by nanoscale block copolymer micelles. (United States)

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


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

  20. The influence of bile acids on the oral bioavailability of vitamin K encapsulated in polymeric micelles. (United States)

    van Hasselt, P M; Janssens, G E P J; Slot, T K; van der Ham, M; Minderhoud, T C; Talelli, M; Akkermans, L M; Rijcken, C J F; van Nostrum, C F


    The purpose of this study was to assess the ability of polymeric micelles to enable gastrointestinal absorption of the extremely hydrophobic compound vitamin K, by comparison of its absorption in bile duct ligated and sham operated rats. Hereto, vitamin K was encapsulated in micelles composed of mPEG(5000)-b-p(HPMAm-lac(2)), a thermosensitive block copolymer. Vitamin K plasma levels rose significantly upon gastric administration of 1 mg vitamin K encapsulated in polymeric micelles in sham operated rats, but not after bile duct ligation (AUC 4543 and 1.64 ng/mL/h respectively, pvitamin K from polymeric micelles is mediated by free bile and that uptake of intact micelles through pinocytosis is insignificant.

  1. Effects of bile salts on percolation and size of AOT reversed micelles. (United States)

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


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

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

    Institute of Scientific and Technical Information of China (English)

    杨楚芬; 孙尧; 章莉娟; 朱国典; 张灿阳; 钱宇


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

  3. Effective repair of traumatically injured spinal cord by nanoscale block copolymer micelles (United States)

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


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

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

    Indian Academy of Sciences (India)

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


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

  5. Micelle structural studies on oil solubilization by a small-angle neutron scattering

    Energy Technology Data Exchange (ETDEWEB)

    Putra, Edy Giri Rachman [Neutron Science Division, HANARO Center, Korea Atomic Energy Research Institute (KAERI), 1045 Daedok-daero, Yuseong-gu, Daejeon 305-353 (Korea, Republic of); Neutron Scattering Laboratory, National Nuclear Energy Agency of Indonesia (BATAN), Gedung 40 Kawasan Puspiptek Serpong, Tangerang 15314 (Indonesia)], E-mail:; Seong, Baek Seok [Neutron Science Division, HANARO Center, Korea Atomic Energy Research Institute (KAERI), 1045 Daedok-daero, Yuseong-gu, Daejeon 305-353 (Korea, Republic of); Ikram, Abarrul [Neutron Scattering Laboratory, National Nuclear Energy Agency of Indonesia (BATAN), Gedung 40 Kawasan Puspiptek Serpong, Tangerang 15314 (Indonesia)


    A small-angle neutron scattering (SANS) technique was applied to reveal the micelle structural changes. The micelle structural changes of 0.3 M sodium dodecyl sulfate (SDS) concentration by addition of various oil, i.e. n-hexane, n-octane, and n-decane up to 60% (v/v) have been investigated. It was found that the size, aggregation number and the structures of the micelles changed exhibiting that the effective charge on the micelle decreases with an addition of oil. There was a small increase in minor axis of micelle while the correlation peak shifted to a lower momentum transfer Q and then to higher Q by a further oil addition.

  6. Factors affecting the stability of drug-loaded polymeric micelles and strategies for improvement (United States)

    Zhou, Weisai; Li, Caibin; Wang, Zhiyu; Zhang, Wenli; Liu, Jianping


    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.

  7. Tumor homing indocyanine green encapsulated micelles for near infrared and photoacoustic imaging of tumors. (United States)

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


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

  8. Synthesis of Cross-Linked Polymeric Micelle pH Nanosensors

    DEFF Research Database (Denmark)

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


    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. Light and phospholipid driven structural transitions in nematic microdroplets

    Energy Technology Data Exchange (ETDEWEB)

    Dubtsov, A. V., E-mail:; Pasechnik, S. V.; Shmeliova, D. V. [Moscow State University of Instrument Engineering and Computer Science, Stromynka 20, Moscow 107996 (Russian Federation); Kralj, Samo [Condensed Matter Physics Department, Jožef Stefan Institute, Jamova 39, 1000 Ljubljana (Slovenia); FNM, University of Maribor, Koroska 160, 2000 Maribor (Slovenia)


    We studied the UV-irradiation and phospholipid driven bipolar-radial structural transitions within azoxybenzene nematic liquid crystal (LC) droplets dispersed in water. It was found that the UV-irradiation induced trans-cis isomerisation of LC molecules could enable structural transitions into radial-type configurations at a critical UV-irradiation time t{sub c}. In particular, we show that under appropriate conditions, a value of t{sub c} could sensitively fingerprint the concentration of phospholipid molecules present in LC-water dispersions. This demonstrated proof-of-principle mechanism could be exploited for development of sensitive detectors for specific nanoparticles (NPs), where value of t{sub c} reveals concentration of NPs.

  10. Elliptical structure of phospholipid bilayer nanodiscs encapsulated by scaffold proteins

    DEFF Research Database (Denmark)

    Skar-Gislinge, Nicholas; Simonsen, Jens Bæk; Mortensen, Kell


    -angle neutron scattering in combination with variable-temperature studies of synchrotron small-angle X-ray scattering on nanodiscs in solution, we show that the fundamental nanodisc unit, consisting of a lipid bilayer surrounded by amphiphilic scaffold proteins, possesses intrinsically an elliptical shape....... The temperature dependence of the curvature of the nanodiscs prepared with two different phospholipid types (DLPC and POPC) shows that it is the scaffold protein that determines the overall elliptical shape and that the nanodiscs become more circular with increasing temperature. Our data also show...... that the hydrophobic bilayer thickness is, to a large extent, dictated by the scaffolding protein and adjusted to minimize the hydrophobic mismatch between protein and phospholipid. Our conclusions result from a new comprehensive and molecular-based model of the nanodisc structure and the use of this to analyze...

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

    Institute of Scientific and Technical Information of China (English)

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


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

  12. Interaction of SynaptotagminⅠ with Phospholipid Membrane: A Monolayer Study

    Institute of Scientific and Technical Information of China (English)

    贺雨虹; 隋森芳


    Synaptotagmin Ⅰ(sytⅠ) is an abundant integral membrane protein of the synaptic vesicle and the C2A domain is an important functional domain in the cytoplasmic part of sytⅠ. C2A prefers to interact with plasmic membranes of neuron cells in vivo and such interaction is closely related to the sytⅠ physiological function as a Ca2+ sensor in the Ca2+-regulated neurotransmitter release. However, the interaction nature between C2A and phospholipids is not well understood. Monolayers at an air/water interface were used to study the interaction between C2A and a phospholipid membrane. The results show that C2A preferentially inserts into the negatively charged phosphatidylserine monolayer and Ca2+ ions are required for the interaction. Electrostatic force is mostly responsible for the insertion of C2A into dipalmitoyl phosphatidylserine monolayers.

  13. Interactions Mode of Amphoteric Molecules with Ordered Phospholipid Membrane

    Institute of Scientific and Technical Information of China (English)

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


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

  14. Curcumin-loaded biodegradable polymeric micelles for colon cancer therapy in vitro and in vivo (United States)

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


    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 colon carcinoma through inhibiting angiogenesis and directly killing cancer cells.

  15. PEG-OCL micelles for quercetin solubilization and inhibition of cancer cell growth. (United States)

    Khonkarn, Ruttiros; Mankhetkorn, Samlee; Hennink, Wim E; Okonogi, Siriporn


    In this study, quercetin (QCT), a flavonoid with high anticancer potential, was loaded into polymeric micelles of PEG-OCL (poly(ethylene glycol)-b-oligo(ε-caprolactone)) with naphthyl or benzyl end groups in order to increase its aqueous solubility. The cytostatic activity of the QCT-loaded micelles toward different human cancer cell lines and normal cells was investigated. The results showed that the solubility of QCT entrapped in mPEG750-b-OCL micelles was substantially increased up to 1 mg/ml, which is approximately 110 times higher than that of its solubility in water (9 μg/ml). The average particle size of QCT-loaded micelles ranged from 14 to 19 nm. The QCT loading capacity of the polymeric micelles with naphthyl groups was higher than that with benzyl groups (10% and 6%, respectively). QCT-loaded, benzyl- and naphthyl-modified micelles effectively inhibited the growth of both sensitive and resistance cancer cells (human erythromyelogenous leukemia cells (K562) and small lung carcinoma cells (GLC4)). However, the benzyl-modified micelles have a good cytocompatibility (in the concentration range investigated (up to 100 μg/ml), they are well tolerated by living cells), whereas their naphthyl counterparts showed some cytotoxicity at higher concentrations (60-100 μg/ml). Flow cytometry demonstrated that the mechanism underlying the growth inhibitory effect of QCT in its free form was inducing cell cycle arrest at the G2/M phase. Benzyl-modified micelles loaded with QCT also exhibited this cycle arresting the effect of cancer cells. In conclusion, this paper shows the enhancement of solubility and cell cycle arrest of QCT loaded into micelles composed of mPEG750-b-OCL modified with benzyl end groups. These micelles are therefore considered to be an attractive vehicle for the (targeted) delivery of QCT to tumors.

  16. Preparation of stable spherical micelles with rigid backbones based on polyaryletherketone copolymers containing lateral pyridyl groups

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Shuling; Liu, Lingzhi; Guo, Yunliang; Jiang, Zhenhua; Wang, Guibin, E-mail:


    A new bisphenol monomer, 3-(3,4-dihydroxyphenylimine) pyridine (PYPH), was synthesized via a deoxidization reaction of an amine. A series of novel polyaryletherketone copolymers containing lateral pyridyl groups (PY-PAEKs) based on PYPH, 2,2-di(4-hydroxyphenyl)propane and 4,4′-difluorobenzophenone were prepared by nucleophilic aromatic substitution polycondensation reactions. Furthermore, spherical micelles with rigid PY-PAEKs as the inner cores and flexible polyacrylic acid (PAA) as the outer shells were obtained in a selective solvent (H{sub 2}O) successfully. The formation of the spherical micelles was confirmed by scanning electron and transmission electron microscopy as well as by surface tension measurements. The formation and size of the spherical micelles depended on the weight ratio of PAA/PY-PAEK, the concentration and pH value of the mixed solution containing the PY-PAEK and PAA, and the number of pyridyl groups in the PY-PAEK. The structure of the spherical micelles could be stabilized by a cross-linking reaction between the pyridyl groups of the PY-PAEKs and 1,4-dibromobutane. The diameter of the spherical micelles decreased because of the removal of the PAA shell from the PY-PAEK core after the cross-linking reaction. The resulting stable spherical micelles with rigid backbones did not dissolve in a number of polar solvents and remained unaffected by changes in the pH values. - Graphical abstract: Display Omitted - Highlights: • Polyaryletherketone copolymers containing lateral pyridyl groups were synthesized. • Spherical micelles were prepared using these copolymers and polyacrylic acid. • The copolymers and polyacrylic acid formed the core and the shell of the micelles, respectively. • The obtained micelles were stabilized by a cross-linking reaction. • The cross-linked micelles had rigid backbones, independent of solvents and pH values.

  17. Equilibrium insertion of nanoscale objects into phospholipid bilayers

    CERN Document Server

    Pogodin, Sergey


    Certain membrane proteins, peptides, nanoparticles and nanotubes have rigid structure and fixed shape. They are often viewed as spheres and cylinders with certain surface properties. Single Chain Mean Field theory is used to model the equilibrium insertion of nanoscale spheres and rods into the phospholipid bilayer. The equilibrium structures and the resulting free energies of the nano-objects in the bilayer allow to distinguish different orientations in the bilayer and estimate the energy barrier of insertion.

  18. Effect of dipolar-angle on phospholipid assembly

    CERN Document Server

    Paul, Tanay


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

  19. Phospholipid and Respiratory Quinone Analyses From Extreme Environments (United States)

    Pfiffner, S. M.


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

  20. Peroxidase activation of cytoglobin by anionic phospholipids: Mechanisms and consequences. (United States)

    Tejero, Jesús; Kapralov, Alexandr A; Baumgartner, Matthew P; Sparacino-Watkins, Courtney E; Anthonymutu, Tamil S; Vlasova, Irina I; Camacho, Carlos J; Gladwin, Mark T; Bayir, Hülya; Kagan, Valerian E


    Cytoglobin (Cygb) is a hexa-coordinated hemoprotein with yet to be defined physiological functions. The iron coordination and spin state of the Cygb heme group are sensitive to oxidation of two cysteine residues (Cys38/Cys83) and/or the binding of free fatty acids. However, the roles of redox vs lipid regulators of Cygb's structural rearrangements in the context of the protein peroxidase competence are not known. Searching for physiologically relevant lipid regulators of Cygb, here we report that anionic phospholipids, particularly phosphatidylinositolphosphates, affect structural organization of the protein and modulate its iron state and peroxidase activity both conjointly and/or independently of cysteine oxidation. Thus, different anionic lipids can operate in cysteine-dependent and cysteine-independent ways as inducers of the peroxidase activity. We establish that Cygb's peroxidase activity can be utilized for the catalysis of peroxidation of anionic phospholipids (including phosphatidylinositolphosphates) yielding mono-oxygenated molecular species. Combined with the computational simulations we propose a bipartite lipid binding model that rationalizes the modes of interactions with phospholipids, the effects on structural re-arrangements and the peroxidase activity of the hemoprotein.

  1. Antioxidant effect of lutein towards phospholipid hydroperoxidation in human erythrocytes. (United States)

    Nakagawa, Kiyotaka; Kiko, Takehiro; Hatade, Keijiro; Sookwong, Phumon; Arai, Hiroyuki; Miyazawa, Teruo


    Peroxidised phospholipid-mediated cytotoxity is involved in the pathophysiology of many diseases; for example, phospholipid hydroperoxides (PLOOH) are abnormally increased in erythrocytes of dementia patients. Dietary carotenoids (especially xanthophylls, polar carotenoids such as lutein) have gained attention as potent inhibitors against erythrocyte phospholipid hydroperoxidation, thereby making them plausible candidates for preventing diseases (i.e. dementia). To evaluate these points, we investigated whether orally administered lutein is distributed to human erythrocytes, and inhibits erythrocyte PLOOH formation. Six healthy subjects took one capsule of food-grade lutein (9.67 mg lutein per capsule) once per d for 4 weeks. Before and during the supplementation period, carotenoids and PLOOH in erythrocytes and plasma were determined by our developed HPLC technique. The administered lutein was incorporated into human erythrocytes, and erythrocyte PLOOH level decreased after the ingestion for 2 and 4 weeks. The antioxidative effect of lutein was confirmed on erythrocyte membranes, but not in plasma. These results suggest that lutein has the potential to act as an important antioxidant molecule in erythrocytes, and it thereby may contribute to the prevention of dementia. Therefore future biological and clinical studies will be required to evaluate the efficacy as well as safety of lutein in models of dementia with a realistic prospect of its use in human therapy.

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

    Directory of Open Access Journals (Sweden)



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

  3. The cation content of phospholipides from swine erythrocytes. (United States)



    Phospholipides from swine erythrocytes were isolated and separated into four reproducible fractions. One of the fractions seems to be pure phosphatidylserine. The others are almost certainly not single compounds, although the analytical data indicate that they represent mixtures considerably simpler than the parent mixture extracted from the cells. All four fractions contained Na(+) and K(+), but very little Ca(2+). Sodium was the predominant cation in two of the fractions under all conditions although the major intracellular cation was potassium. In the other two fractions the ratio Na/K varied with the extraction procedure largely because the quantity of K(+) seemed to depend on the solvent system used. There appear to be reasons to believe that the entire system of phospholipides binds Na(+) preferentially. In addition, it was observed that the quantity of Na(+) found in the lipide extracts varied when the extrusion of Na(+) from the cells was made to vary. Both of these observations are consistent with the possibility that the phospholipides play some part in the extrusion of Na(+) from these cells.

  4. Penetration of surfactin into phospholipid monolayers: nanoscale interfacial organization. (United States)

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


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

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

    Directory of Open Access Journals (Sweden)

    Chung-Ming Chen


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

  6. Enteropathogenic Escherichia coli infection triggers host phospholipid metabolism perturbations. (United States)

    Wu, Y; Lau, B; Smith, S; Troyan, K; Barnett Foster, D E


    Enteropathogenic Escherichia coli (EPEC) specifically recognizes phosphatidylethanolamine (PE) on the outer leaflet of host epithelial cells. EPEC also induces apoptosis in epithelial cells, which results in increased levels of outer leaflet PE and increased bacterial binding. Consequently, it is of interest to investigate whether EPEC infection perturbs host cell phospholipid metabolism and whether the changes play a role in the apoptotic signaling. Our findings indicate that EPEC infection results in a significant increase in the epithelial cell PE level and a corresponding decrease in the phosphatidylcholine (PC) level. PE synthesis via both the de novo pathway and the serine decarboxylation pathway was enhanced, and de novo synthesis of phosphatidylcholine via CDP-choline was reduced. The changes were transitory, and the maximum change was noted after 4 to 5 h of infection. Addition of exogenous PC or CDP-choline to epithelial cells prior to infection abrogated EPEC-induced apoptosis, suggesting that EPEC infection inhibits the CTP-phosphocholine cytidylyltransferase step in PC synthesis, which is reportedly inhibited during nonmicrobially induced apoptosis. On the other hand, incorporation of exogenous PE by the host cells enhanced EPEC-induced apoptosis and necrosis without increasing bacterial adhesion. This is the first report that pathogen-induced apoptosis is associated with significant changes in PE and PC metabolism, and the results suggest that EPEC adhesion to a host membrane phospholipid plays a role in disruption of host phospholipid metabolism.

  7. Nonenzymatic biomimetic remodeling of phospholipids in synthetic liposomes. (United States)

    Brea, Roberto J; Rudd, Andrew K; Devaraj, Neal K


    Cell membranes have a vast repertoire of phospholipid species whose structures can be dynamically modified by enzymatic remodeling of acyl chains and polar head groups. Lipid remodeling plays important roles in membrane biology and dysregulation can lead to disease. Although there have been tremendous advances in creating artificial membranes to model the properties of native membranes, a major obstacle has been developing straightforward methods to mimic lipid membrane remodeling. Stable liposomes are typically kinetically trapped and are not prone to exchanging diacylphospholipids. Here, we show that reversible chemoselective reactions can be harnessed to achieve nonenzymatic spontaneous remodeling of phospholipids in synthetic membranes. Our approach relies on transthioesterification/acyl shift reactions that occur spontaneously and reversibly between tertiary amides and thioesters. We demonstrate exchange and remodeling of both lipid acyl chains and head groups. Using our synthetic model system we demonstrate the ability of spontaneous phospholipid remodeling to trigger changes in vesicle spatial organization, composition, and morphology as well as recruit proteins that can affect vesicle curvature. Membranes capable of chemically exchanging lipid fragments could be used to help further understand the specific roles of lipid structure remodeling in biological membranes.

  8. Compound exocytosis of casein micelles in mammary epithelial cells. (United States)

    Dylewski, D P; Keenan, T W


    Ultrastructure of lactating bovine and rat mammary epithelial cells was studied with emphasis on secretory vesicle interactions. In the apical zone of the cell, adjacent secretory vesicles formed ball and socket configurations at their points of apposition. Similar configurations were formed between plasma membrane and secretory vesicle membrane. These structures may be formed by the diffusion of water between vesicles with different osmotic potentials. Frequently, vesicular chains consisting of 10 or more linked secretory vesicles were observed. Prior to the exocytotic release of casein micelles, adjacent vesicles fused through fragmentation of the ball and socket membrane. These membrane fragments and the casein micelles appeared to be secreted into the alveolar lumen after passing from one vesicle into another and finally through a pore in the apical plasma membrane. Emptied vesicular chains appeared to collapse and fragmentation of their membrane was observed. Based on these observations, we suggest that most vesicular membrane does not directly contact or become incorporated into the plasma membrane during secretion of the nonfat phase of milk.

  9. Micelle assisted structural conversion with fluorescence modulation of benzophenanthridine alkaloids (United States)

    Pradhan, Ankur Bikash; Bhuiya, Sutanwi; Haque, Lucy; Tiwari, Richa; Das, Suman


    In this study we have reported the anionic surfactant (Sodium dodecyl sulfate, SDS) driven structural conversion of two benzophenanthridine plant alkaloids namely Chelerythrine (herein after CHL) and Sanguinarine (herein after SANG). Both the alkaloids exist in two forms: the charged iminium and the neutral alkanolamine form. The iminium form is stable at low pH ( 10.1). The fluorescence intensity of the alkanolamine form is much stronger than the iminium form. The iminium form of both the alkaloids remains stable whereas the alkanolamine form gets converted to the iminium form in the SDS micelle environment. The iminium form possesses positive charge and it seems that electrostatic interaction between the positively charged iminium and negatively charged surfactant leads to the stabilization of the iminium form in the Stern layer of the anionic micelle. Whereas the conversion of the alkanolamine form into the iminium form takes place and that can be monitored in naked eye since the iminium form is orange in colour and the alkanolamine form has blue violet emission. Such a detail insight about the photophysical properties of the benzophenanthridine alkaloids would be a valuable addition in the field of alkaloid-surfactant interaction.

  10. Skin delivery by block copolymer nanoparticles (block copolymer micelles). (United States)

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


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

  11. Encapsulation of GFP in Complex Coacervate Core Micelles. (United States)

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


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

  12. Molecular exchange in block copolymer micelles: when corona chains overlap (United States)

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


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

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

    Directory of Open Access Journals (Sweden)

    M. Gavella


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

  14. Electron paramagnetic resonance studies of magnetically aligned phospholipid bilayers utilizing a phospholipid spin label: the effect of cholesterol. (United States)

    Dave, Paresh C; Nusair, Nisreen A; Inbaraj, Johnson J; Lorigan, Gary A


    X-band EPR spectroscopy has been employed to study the dynamic properties of magnetically aligned phospholipid bilayers (bicelles) utilizing a variety of phosphocholine spin labels (n-PCSL) as a function of cholesterol content. The utilization of both perpendicular and parallel aligned bicelles in EPR spectroscopy provides a more detailed structural and orientational picture of the phospholipid bilayers. The magnetically aligned EPR spectra of the bicelles and the hyperfine splitting values reveal that the addition of cholesterol increases the phase transition temperature and alignment temperature of the DMPC/DHPC bicelles. The corresponding molecular order parameter, Smol, of the DMPC/DHPC bicelles increased upon addition of cholesterol. Cholesterol also decreased the rotational motion and increased the degree of anisotropy in the interior region of the bicelles. This report reveals that the dynamic properties of DMPC/DHPC bicelles agree well with other model membrane systems and that the magnetically aligned bicelles are an excellent model membrane system.

  15. Aqueous solutions at the interface with phospholipid bilayers. (United States)

    Berkowitz, Max L; Vácha, Robert


    In a sense, life is defined by membranes, because they delineate the barrier between the living cell and its surroundings. Membranes are also essential for regulating the machinery of life throughout many interfaces within the cell's interior. A large number of experimental, computational, and theoretical studies have demonstrated how the properties of water and ionic aqueous solutions change due to the vicinity of membranes and, in turn, how the properties of membranes depend on the presence of aqueous solutions. Consequently, understanding the character of aqueous solutions at their interface with biological membranes is critical to research progress on many fronts. The importance of incorporating a molecular-level description of water into the study of biomembrane surfaces was demonstrated by an examination of the interaction between phospholipid bilayers that can serve as model biological membranes. The results showed that, in addition to well-known forces, such as van der Waals and screened Coulomb, one has to consider a repulsion force due to the removal of water between surfaces. It was also known that physicochemical properties of biological membranes are strongly influenced by the specific character of the ions in the surrounding aqueous solutions because of the observation that different anions produce different effects on muscle twitch tension. In this Account, we describe the interaction of pure water, and also of aqueous ionic solutions, with model membranes. We show that a symbiosis of experimental and computational work over the past few years has resulted in substantial progress in the field. We now better understand the origin of the hydration force, the structural properties of water at the interface with phospholipid bilayers, and the influence of phospholipid headgroups on the dynamics of water. We also improved our knowledge of the ion-specific effect, which is observed at the interface of the phospholipid bilayer and aqueous solution, and its

  16. 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.


    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...... concentrations in the dilute and semidilute regime cover approximately three decades of scattering vectors. The data have been analyzed using polymer renormalization-group theory and a nonlinear least-squares fitting procedure based upon a numerical expression for the single chain scattering function...... transformation and square-root deconvolution techniques. We demonstrate that we can determine structural properties such as the micellar cross-section profile and flexibility as well as quantitatively incorporate the influence of micellar growth and excluded-volume effects on S(q,c)....

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

    Energy Technology Data Exchange (ETDEWEB)

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


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

  18. Extraction of lysozyme, alpha-chymotrypsin, and pepsin into reverse micelles formed using an anionic surfactant, isooctane, and water. (United States)

    Chang, Q; Liu, H; Chen, J


    The extraction of lysozyme, alpha-chymotrypsin, and pepsin from buffered salt solutions into reverse micelles was examined at different pH values and surfactant concentrations. The reverse micelles was formed by mixing aqueous buffer supplemented with KCl and an organic phase of isooctane(2,2,4-trimethylpentane), containing the anionic surfactant, Aerosol O. T. (dioctyl ester of sodium sulfosuccinic acid). The technique of dynamic laser scattering was used to measure the size of reverse micelles which were in equilibrium with the aqueous phase. It was found that the size of the reverse micelles decreased with increasing ionic strength but increased with increasing AOT concentration. In the process of extraction, the reverse micelles might have rearranged themselves to host the protein. The sizes of protein-filled and -unfilled reverse micelles were different, and an open equilibrium could be reached between them. Under the extraction conditions, only a small number of micelles were found to contain protein.

  19. Production of Fluconazole-Loaded Polymeric Micelles Using Membrane and Microfluidic Dispersion Devices (United States)

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


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

  20. Thermal responsive micelles for dual tumor-targeting imaging and therapy (United States)

    Chen, Haiyan; Li, Bowen; Qiu, Jiadan; Li, Jiangyu; Jin, Jing; Dai, Shuhang; Ma, Yuxiang; Gu, Yueqing


    Two kinds of thermally responsive polymers P(FAA-NIPA-co-AAm-co-ODA) and P(FPA-NIPA-co-AAm-co-ODA) containing folate, isopropyl acrylamide and octadecyl acrylate were fabricated through free radical random copolymerization for targeted drug delivery. Then the micelles formed in aqueous solution by self-assembly and were characterized in terms of particle size, lower critical solution temperature (LCST) and a variety of optical spectra. MTT assays demonstrated the low cytotoxicity of the control micelle and drug-loaded micelle on A549 cells and Bel 7402 cells. Then fluorescein and cypate were used as model drugs to optimize the constituents of micelles for drug entrapment efficiency and investigate the release kinetics of micelles in vitro. The FA and thermal co-mediated tumor-targeting efficiency of the two kinds of micelles were verified and compared in detail at cell level and animal level, respectively. These results indicated that the dual-targeting micelles are promising drug delivery systems for tumor-targeting therapy.

  1. How to squeeze a sponge: casein micelles under osmotic stress, a SAXS study. (United States)

    Bouchoux, Antoine; Gésan-Guiziou, Geneviève; Pérez, Javier; Cabane, Bernard


    By combining the osmotic stress technique with small-angle x-ray scattering measurements, we followed the structural response of the casein micelle to an overall increase in concentration. When the aqueous phase that separates the micelles is extracted, they behave as polydisperse repelling spheres and their internal structure is not affected. When they are compressed, the micelles lose water and shrink to a smaller volume. Our results indicate that this compression is nonaffine, i.e., some parts of the micelle collapse, whereas other parts resist deformation. We suggest that this behavior is consistent with a spongelike casein micelle having a triple hierarchical structure. The lowest level of the structure consists of the CaP nanoclusters that serve as anchors for the casein molecules. The intermediate level consists of 10- to 40-nm hard regions that resist compression and contain the nanoclusters. Those regions are connected and/or partially merged with each other, thus forming a continuous and porous material. The third level of structure is the casein micelle itself, with an average size of 100 nm. In our view, such a structure is consistent with the observation of 10- to 20-nm casein particles in the Golgi vesicles of lactating cells: upon aggregation, those particles would rearrange, fuse, and/or swell to form the spongelike micelle.

  2. Octreotide-functionalized and resveratrol-loaded unimolecular micelles for targeted neuroendocrine cancer therapy (United States)

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


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

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

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


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

  4. A micelle-like structure of poloxamer-methotrexate conjugates as nanocarrier for methotrexate delivery. (United States)

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


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

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

    Directory of Open Access Journals (Sweden)

    Yu Lu


    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.

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

    Institute of Scientific and Technical Information of China (English)

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


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

  7. Thermo-sensitive complex micelles from sodium alginate-graft-poly(N-isopropylacrylamide) for drug release. (United States)

    Yu, Nana; Li, Guiying; Gao, Yurong; Jiang, Hua; Tao, Qian


    Polymer micelles with environmentally sensitive properties have potential applications in biomedicine. In this paper, thermo-sensitive complex micelles assembled from biocompatible graft copolymers sodium alginate-graft-poly(N-isopropylacrylamide) (SA-g-PNIPAM) and divalent metal ions were prepared for controlled drug release. The polymer micelles had core-corona structure, which was constituted by metal ions (Ba(2+), Zn(2+), Co(2+)) cross-linked sodium alginate as the core and thermo-sensitive PNIPAM chains as the corona. Formation of polymer micelles was determined by Fourier-transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM) and dynamic light scattering (DLS). The polymer micelles were observed as regular spheres with good polydispersity and excellent performance on drug encapsulation and release ability. The cumulative release of 5-fluorouracil (5-FU) from micelles was controlled by pH, ionic strength or temperature of surroundings. The superior properties of sensitive polymer micelles induced by metal ions are expected to be utilized in controlled drug delivery systems.

  8. Study of sodium dodecyl sulfate-poly(propylene oxide) methacrylate mixed micelles. (United States)

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


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

  9. Synthesis of sn-1 functionalized phospholipids as substrates for secretory phospholipase A2

    DEFF Research Database (Denmark)

    Linderoth, Lars; Peters, Günther H.J.; Jørgensen, K.;


    Secretory phospholipase A2 (sPLA2) represents a family of small water-soluble enzymes that catalyze the hydrolysis of phospholipids in the sn-2 position liberating free fatty acids and lysophospholipids. Herein we report the synthesis of two new phospholipids (1 and 2) with bulky allyl......-substituents attached to the sn-1 position of the glycerol backbone. The synthesis of phospholipids 1 and 2 is based upon the construction of a key aldehyde intermediate 3 which locks the stereochemistry in the sn-2 position of the final phospholipids. The aldehyde functionality serves as the site for insertion...... of the allyl-substituents by a zinc mediated allylation. Small unilamellar liposomes composed of phospholipids 1 and 2 were subjected to sPLA2 activity measurements. Our results show that only phospholipid 1 is hydrolyzed by the enzyme. Molecular dynamics simulations revealed that the lack of hydrolysis...

  10. Composition and fatty acid distribution of bovine milk phospholipids from processed milk products. (United States)

    Gallier, Sophie; Gragson, Derek; Cabral, Charles; Jiménez-Flores, Rafael; Everett, David W


    The aim of this work was to assess the accuracy of different extraction methods of phospholipids and to measure the effect that processing has on phospholipid composition. Four methods of extracting phospholipids from buttermilk powder were compared to optimize recovery of sphingomyelin. Using the optimal method, the phospholipid profile of four dairy products (raw milk, raw cream, homogenized and pasteurized milk, and buttermilk powder) was determined. A total lipid extraction by the Folch method followed by a solid-phase extraction using the Bitman method was the most efficient technique to recover milk sphingomyelin. Milk processing (churning, centrifuging, homogenization, spray-drying) affected the profile of milk phospholipids, leading to a loss of sphingomyelin and phosphatidylcholine after centrifugation for cream separation. A corresponding decrease in the saturation content of the raw cream phospholipids and a loss of phosphatidylethanolamine after spray-drying to produce buttermilk powder were also observed.

  11. Novel micelle formulation of curcumin for enhancing antitumor activity and inhibiting colorectal cancer stem cells

    Directory of Open Access Journals (Sweden)

    Wang K


    Full Text Available Ke Wang,1 Tao Zhang,1 Lina Liu,2 Xiaolei Wang,1 Ping Wu,1 Zhigang Chen,1 Chao Ni,1 Junshu Zhang,1 Fuqiang Hu,4 Jian Huang1,31Cancer Institute, 2Department of Pharmacy, Second Affiliated Hospital (Binjiang Branch, 3Department of Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, 4College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, ChinaBackground and methods: Curcumin has extraordinary anticancer properties but has limited use due to its insolubility in water and instability, which leads to low systemic bioavailability. We have developed a novel nanoparticulate formulation of curcumin encapsulated in stearic acid-g-chitosan oligosaccharide (CSO-SA polymeric micelles to overcome these hurdles.Results: The synthesized CSO-SA copolymer was able to self-assemble to form nanoscale micelles in aqueous medium. The mean diameter of the curcumin-loaded CSO-SA micelles was 114.7 nm and their mean surface potential was 18.5 mV. Curcumin-loaded CSO-SA micelles showed excellent internalization ability that increased curcumin accumulation in cancer cells. Curcumin-loaded CSO-SA micelles also had potent antiproliferative effects on primary colorectal cancer cells in vitro, resulting in about 6-fold greater inhibition compared with cells treated with a solution containing an equivalent concentration of free curcumin. Intravenous administration of curcumin-loaded CSO-SA micelles marginally suppressed tumor growth but did not increase cytotoxicity to mice, as confirmed by no change in body weight. Most importantly, curcumin-loaded CSO-SA micelles were effective for inhibiting subpopulations of CD44+/CD24+ cells (putative colorectal cancer stem cell markers both in vitro and in vivo.Conclusion: The present study identifies an effective and safe means of using curcumin-loaded CSO-SA micelles for cancer therapy.Keywords: chitosan oligosaccharide, polymeric micelle, curcumin, drug delivery, colorectal cancer, cancer stem cells

  12. Backbone-hydrazone-containing biodegradable copolymeric micelles for anticancer drug delivery (United States)

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


    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.

  13. Catalytic performance and thermostability of chloroperoxidase in reverse micelle: achievement of a catalytically favorable enzyme conformation. (United States)

    Wang, Yali; Wu, Jinyue; Ru, Xuejiao; Jiang, Yucheng; Hu, Mancheng; Li, Shuni; Zhai, Quanguo


    The catalytic performance of chloroperoxidase (CPO) in peroxidation of 2, 2'-azinobis-(-3 ethylbenzothiazoline-6-sulfononic acid) diammonium salt (ABTS) and oxidation of indole in a reverse micelle composed of surfactant-water-isooctane-pentanol was investigated and optimized in this work. Some positive results were obtained as follows: the peroxidation activity of CPO was enhanced 248% and 263%, while oxidation activity was enhanced 215% and 222% in cetyltrimethylammonium bromide (CTABr) reverse micelle medium and dodecyltrimethylammonium bromide (DTABr) medium, respectively. Thermostability was also greatly improved in reverse micelle: at 40 °C, CPO essentially lost all its activity after 5 h incubation, while 58-76% catalytic activity was retained for both reactions in the two reverse micelle media. At 50 °C, about 44-75% catalytic activity remained for both reactions in reverse micelle after 2 h compared with no observed activity in pure buffer under the same conditions. The enhancement of CPO activity was dependent mainly on the surfactant concentration and structure, organic solvent ratio (V(pentanol)/V(isooctane)), and water content in the reverse micelle. The obtained kinetic parameters showed that the catalytic turnover frequency (k(cat)) was increased in reverse micelle. Moreover, the lower K(m) and higher k(cat)/K(m) demonstrated that both the affinity and specificity of CPO to substrates were improved in reverse micelle media. Fluorescence, circular dichroism (CD) and UV-vis spectra assays indicated that a catalytically favorable conformation of enzyme was achieved in reverse micelle, including the strengthening of the protein α-helix structure, and greater exposure of the heme prosthetic group for easy access of the substrate in bulk solution. These results are promising in view of the industrial applications of this versatile biological catalyst.

  14. The Effect of Hydrophilic and Hydrophobic Structure of Amphiphilic Polymeric Micelles on Their Transportation in Rats. (United States)

    Deng, Feiyang; Yu, Chao; Zhang, Hua; Dai, Wenbing; He, Bing; Zheng, Ying; Wang, Xueqing; Zhang, Qiang


    In the previous study, we have clarified how the hydrophilic and hydrophobic structures of amphiphilic polymers impact the transport of their micelles (PEEP-PCL, PEG-PCL and PEG-DSPE micelles) in epithelial MDCK cells (Biomaterials 2013, 34: 6284-6298). In this study, we attempt to clarify the behavior of the three micelles in rats. Coumarin-6 loaded micelles were injected into different sections of intestine of rats and observed by confocal laser scanning microscope (CLSM) or orally administrated and conducted pharmacokinetic study. All of the three kinds of micelles were able to cross the intestinal epithelial cells and enter blood circulation. The PEEP-PCL micelles demonstrated the fastest distribution mainly in duodenum, while the PEGDSPE micelles showed the longest distribution with the highest proportion in ileum of the three. No significant difference was observed among the pharmacokinetic parameters of the three micelles. The results were consistent in the two analysis methods mentioned above, yet there were some differences between in vivo and in vitro results reported previously. It might be the distinction between the environments in MDCK model and intestine that led to the discrepancy. The hydrophobicity of nanoparticles could both enhance uptake and hinder the transport across the mucus. However, there was no intact mucus in MDCK model, which preferred hydrophobic nanoparticles. PEEP was the most hydrophilic material constructing the micelles in the study and its uptake would be increased in rats compared to that in MDCK model, while DSPE was more hydrophobic than the others and MDCK model would be more ideal for its uptake. Considering the inconsistency of the results in the two models, whether the methods researchers were generally using at present were reasonable needs further investigation.

  15. A review on phospholipids and their main applications in drug delivery systems


    Jing Li; Xuling Wang; Ting Zhang; Chunling Wang; Zhenjun Huang; Xiang Luo; Yihui Deng


    Phospholipids have the characteristics of excellent biocompatibility and a especial amphiphilicity. These unique properties make phospholipids most appropriate to be employed as important pharmaceutical excipients and they have a very wide range of applications in drug delivery systems. The aim of this review is to summarize phospholipids and some of their related applications in drug delivery systems, and highlight the relationship between the properties and applications, and the effect of t...

  16. Phospholipide turnover in microsomal membranes of the pancreas during enzyme secretion. (United States)



    After incubation of pigeon pancreas slices with P(32) and isolation of various fractions by differential centrifugation the deoxycholate extract of the microsome fraction was found to account for over half of the phospholipide P and over half of the P(32) incorporated into the phospholipides. The remaining phospholipide P and P(32) were fairly evenly distributed in the nuclei, zymogen granules, mitochondria, microsomal ribonucleoprotein particles, and the soluble fraction. When enzyme secretion was stimulated with acetylcholine about two-thirds of the increment in radioactivity in the total phospholipides was found in deoxycholate soluble components of the microsome fraction. The remainder of the increment was distributed in the other fractions. This indicates that the cellular component in which the increase in phospholipide turnover occurs on stimulation of secretion is a membranous structure. Evidence is presented which indicates that the increment in radioactivity in the non-microsomal fractions on stimulation of secretion is due to contamination of these fractions with fragments of the stimulated membranous structure. The distribution of P(32) radioactivity in each of the chromatographically separated phospholipides in the various fractions from unstimulated tissue paralleled the distribution of radioactivity in the total phospholipide fraction, indicating that individual phospholipides are not concentrated in different fractions but are associated together in the membranous structures of the microsome fraction. The major proportion of the stimulation of the turnover of the individual phospholipides also occurred in the microsome fraction. The distribution of radioactivity from glycerol-1-C(14) in the total phospholipides and in the individual phospholipides in the various fractions was similar to the distribution of P(32). In the microsome fraction acetylcholine stimulated the incorporation of glycerol-1-C(14) in each phospholipide which showed a stimulation

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

    Institute of Scientific and Technical Information of China (English)

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


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

  18. Dissipative particle dynamics simulation on paclitaxel loaded PEO-PPO-PEO block copolymer micelles. (United States)

    Wang, Zhigao; Jiang, Jie


    Self-assembly behavior of the polymer drug loading micelle PEO-PPO-PEO was studied using dissipative particle dynamics (DPD) simulation method with various simulation steps. The distributions of drugs in polymer carriers were also investigated with different drug feed ratios. Polymer carriers distributed on the surface of the spherical micelle, and drugs were almost encapsulated in the inner of the micelle. Our simulation work demonstrates that the DPD simulation is effective to study the drug loaded systems and can give useful guidance on the design and preparation of new drug carriers with tailored properties.

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


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


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

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

    Indian Academy of Sciences (India)

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


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

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

    Indian Academy of Sciences (India)

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


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

  2. Formation of oil-in-water emulsions from natural emulsifiers using spontaneous emulsification: sunflower phospholipids. (United States)

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


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

  3. Comprehensive approach to the quantitative analysis of mitochondrial phospholipids by HPLC-MS. (United States)

    Kim, Junhwan; Hoppel, Charles L


    A normal-phase HPLC-MS method was established to analyze mitochondrial phospholipids quantitatively as well as qualitatively. An efficient extraction procedure and chromatographic conditions were developed using twelve standardized phospholipids and lysophospholipids. The chromatographic conditions provided physical separation of phospholipids by class, and efficient ionization allowed detection of low abundance phospholipids such as phosphatidylglycerol and monolysocardiolipin. The chromatographic separation of each class of phospholipid permitted qualitative identification of molecular species without interference from other classes. This is advantageous for mitochondrial lipidomics because the composition of mitochondrial phospholipids varies depending on tissue source, pathological condition, and nutrition. Using the method, seven classes of phospholipids (phosphatidylethanolamine, phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol, phosphatidylserine, cardiolipin, and monolysocardiolipin) were detected in rat heart and skeletal muscle mitochondria and all but phosphatidylserine were quantified. The concentration was calculated using standard curves with an internal standard generated for each class of phospholipid. The method was validated for intraday and interday variation and showed excellent reproducibility and accuracy. This new method, with each step documented, provides a powerful tool for accurate quantitation of phospholipids, a basic structural component of mitochondrial membranes.

  4. Update on anti-phospholipid antibodies in SLE: the Hopkins' Lupus Cohort. (United States)

    Petri, M


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

  5. Structure-Property Relationships for Branched Worm-Like Micelles (United States)

    Beaucage, Gregory; Rai, Durgesh


    Micellar solutions can display a wide range of phase structure as a function of counter ion content, surfactant concentration, and the presence of ternary components. Under some conditions, common to consumer products, extended cylindrical structures that display persistence and other chain features of polymers are produced. These worm-like micelles (WLMs) can form branched structures that dynamically change under shear and even in quiescent conditions. The rheology of these branched WLMs is strongly dependent on migration of the branch points, and the dynamics of branch formation and removal. Persistence and other polymer-based descriptions are also of importance. We have recently developed a scattering model for branched polyolefins and other topologically complex materials that can quantify the branching density, branch length, branch functionality and the hyperbranch (branch-on-branch) content of polymers. This work is being extended to study branching in WLMs in work coupled with Ron Larson at UMich to predict rheological properties.

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

    KAUST Repository

    Bukhryakov, Konstantin V.


    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.

  7. Cooperative catalysis with block copolymer micelles: a combinatorial approach. (United States)

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


    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.

  8. Sphingophosphonolipids, phospholipids, and fatty acids from Aegean jellyfish Aurelia aurita. (United States)

    Kariotoglou, D M; Mastronicolis, S K


    The goal of this study is to elucidate and identify several sphingophosphonolipids from Aurelia aurita, an abundant but harmless Aegean jellyfish, in which they have not previously been described. Total lipids of A. aurita were 0.031-0.036% of fresh tissue, and the lipid phosphorus content was 1.3-1.7% of total lipids. Phosphonolipids were 21.7% of phospholipids and consisted of a major ceramide aminoethylphosphonate (CAEP-I; 18.3%), as well as three minor CAEP (II, III, IV) methyl analogs at 1.3, 1.1, and 1.0%, respectively. The remaining phospholipid composition was: phosphatidylcholine, 44.5%, including 36.2% glycerylethers; phosphatidylethanolamine, 18.6%, including 4.5% glycerylethers; cardiolipin, 5.6%; phosphatidylinositol, 2.6%; and lysophosphatidylcholine, 5.0%. In CAEP-I, saturated fatty acids of 14-18 carbon chain length were 70.8% and were combined with 57.3% dihydroxy bases and 23.4% trihydroxy bases. The suite of the three minor CAEP methyl analogs were of the same lipid class based on the head group, but they separated into three different components because of their polarity as follows: CAEP-II and CAEP-III differentiation from the major CAEP-I was mainly due to the increased fatty acid unsaturation and not to a different long-chain base, but the CAEP-IV differentiation from CAEP-I, apart from fatty acid unsaturation, was due to the increased content of hydroxyl groups originated from both hydroxy fatty acids and trihydroxy long-chain bases. Saturated fatty acids were predominant in total (76.7%), polar (83.0%), and neutral lipids (67.6%) of A. aurita. The major phospholipid components of A. aurita were comparable to those previously found in a related organism (Pelagia noctiluca), which can injure humans.

  9. Phospholipid and Hydrocarbon Interactions with a Charged Electrode Interface. (United States)

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


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

  10. Magnetic field alignable domains in phospholipid vesicle membranes containing lanthanides. (United States)

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


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

  11. Solute partitioning in aqueous surfactant assemblies: comparison of hydrophobic-hydrophilic interactions in micelles, alcohol-swollen micelles, microemulsions, and synthetic vesicles

    Energy Technology Data Exchange (ETDEWEB)

    Russell, J.C.; Whitten, D.G.


    The structures of anionic assemblies including sodium lauryl sulfate (SLS) micelles, alcohol-swollen SLS micelles, microemulsions, and vesicles of a mixture of dipalmitoyllecithin and dicetyl phosphate are investigated by using the ground-state complexation of a hydrophilic quencher (methyl viologen) with several hydrophobic fluorescent probes, including surfactant stilbenes and 1,4-diphenylbutadiene. In SLS micelles this complexation can be decreased nearly an order of magnitude by addition of 1-heptanol, indicating that the structure of the micelle can be adjusted from the highly open structure of the pure micelle to a much more closed structure in which hydrophobic solubilizates can be sequestered from hydrophilic reagents bound to the surface. The fluorescence quenching process in anionic vesicles is strongly dependent on temperature; at low temperatures quenching occurs, while at higher temperatures addition of methyl viologen appears to increase the stilbene fluorescence, indicating that the dicationic quencher binds to the vesicle surface, increasing the order of the system. These results indicate that the degree of organization of surfactant systems can be adjusted by simple changes in composition. 33 references.

  12. Formation of Polyion Complex (PIC) Micelles and Vesicles with Anionic pH-Responsive Unimer Micelles and Cationic Diblock Copolymers in Water. (United States)

    Ohno, Sayaka; Ishihara, Kazuhiko; Yusa, Shin-Ichi


    A random copolymer (p(A/MaU)) of sodium 2-(acrylamido)-2-methylpropanesulfonate (AMPS) and sodium 11-methacrylamidoundecanate (MaU) was prepared via conventional radical polymerization, which formed a unimer micelle under acidic conditions due to intramolecular hydrophobic interactions between the pendant undecanoic acid groups. Under basic conditions, unimer micelles were opened up to an expanded chain conformation by electrostatic repulsion between the pendant sulfonate and undecanoate anions. A cationic diblock copolymer (P163M99) consisting of poly(3-(methacrylamido)propyl)trimethylammonium chloride (PMAPTAC) and hydrophilic polybetaine, 2-(methacryloyloxy)ethylphosphorylcholine (MPC), blocks was prepared via controlled radical polymerization. Mixing of p(A/MaU) and P163M99 in 0.1 M aqueous NaCl under acidic conditions resulted in the formation of spherical polyion complex (PIC) micelles and vesicles, depending on polymer concentration before mixing. Shapes of the PIC micelles and vesicles changed under basic conditions due to collapse of the charge balance between p(A/MaU) and P163M99. The PIC vesicles can incorporate nonionic hydrophilic guest molecules, and the PIC micelles and vesicles can accept hydrophobic guest molecules in the hydrophobic core formed from p(A/MaU).

  13. 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)


    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)

  14. Phospholipid bilayer formation at a bare Si surface

    DEFF Research Database (Denmark)

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


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

  15. Antibodies to Phospholipids and Liposomes: Binding of Antibodies to Cells (United States)


    LIPOSOMES: BINDING OF ANTIBODIES TO CELLS 12. PERSONAL AUTHOR(S) W.E. FOGLER , G. M. SWARTZ, AND C.R. ALVING 13a TYPE OF REPORT 13b. TIME COVERED 14. DATE...Elsevier BBA 73693 Antibodies to phospholipids and liposomes: binding of antibodies to cells William E. Fogler *, Glenn M. Swartz, Jr. and Carl R. Alving...Immunol. 21. Research Associateship from the U.S. National 12863-86812Hall. T. and Esser, K. (1984) 3. Immunol. 132. 2059-2063 Research Council. 13 Fogler

  16. Lysophosphatidic acid as a phospholipid mediator: pathways of synthesis. (United States)

    Gaits, F; Fourcade, O; Le Balle, F; Gueguen, G; Gaigé, B; Gassama-Diagne, A; Fauvel, J; Salles, J P; Mauco, G; Simon, M F; Chap, H


    From very recent studies, including molecular cloning of cDNA coding for membrane receptors, lysophosphatidic acid (LPA) reached the status of a novel phospholipid mediator with various biological activities. Another strong argument supporting this view was the discovery that LPA is secreted from activated platelets, resulting in its appearance in serum upon blood coagulation. The metabolic pathways as well as the enzymes responsible for LPA production are poorly characterized. However, a survey of literature data indicates some interesting issues which might be used as the basis for further molecular characterization of phospholipases A able to degrade phosphatidic acid.

  17. Directional Self-assembly in Archaerhodopsin-Reconstituted Phospholipid Liposomes

    Institute of Scientific and Technical Information of China (English)

    吴佳; 黄力; 刘坚; 明明; 李庆国; 丁建东


    This paper reports, for the first time, that Archaerhodopsin-4 (AR4) could be reconstituted into phospholipid liposomes by self-assembly. AR4 is a new membrane protein isolated from halobacteria H.sp. xz515 in a salt lake of Tibet, China. This is a bacteriorhodopsin (bR) like protein, function as a light-driven proton pump. Experimental measurements verified that similar to bR, AR not only remains its biological activity in pmteoliposome, but also keeps a preferred orientation in self-assembly.

  18. Kinetics of the Bicelle to Lamellae Transition in Phospholipid Mixtures (United States)

    Wang, Howard; Nieh, Mu-Ping; Hobbie, Erik K.; Glinka, Charles J.; Katsaras, John


    The kinetics of the bicelle to lamellae transition in phospholipid mixtures of DMPC/DHPC is investigated using time-resolved small-angle neutron scattering. The data suggest that ordering in these mixtures is a multi-stage process, initiated by the coalescence of bicelles into stacked membrane layers, and limited at late time by the coarsening and swelling of stacks and pinning due to defects. The time evolution of the ordering process is quantified via structural scaling of the non-equilibrium structure factor.

  19. Cysteine modified and bile salt based micelles: preparation and application as an oral delivery system for paclitaxel. (United States)

    Xu, Wei; Fan, Xiaohui; Zhao, Yanli; Li, Lingbing


    The aim of the present study is to construct a cysteine modified polyion complex micelles made of Pluronic F127-chitosan (PF127-CS), Pluronic F127-cysteine (PF127-cysteine) and sodium cholate (NaC) and to evaluate the potential of the micelles as an oral drug delivery system for paclitaxel. Systematic studies on physicochemical properties including size distribution, zeta-potential and morphology were conducted to validate the formation of micelle structure. Compared with Pluronic micelles, drug-loading capacity of PF127-CS/PF127-cysteine/NaC micelles was increased from 3.35% to 12.77%. Both the critical micelle concentration and the stability test confirmed that the PF127-CS/PF127-cysteine/NaC micelles were more stable in aqueous solution than sodium cholate micelles. Pharmacokinetic study demonstrated that when oral administration the area under the plasma concentration-time curve (AUC0-∞) and the absolute bioavailability of paclitaxel-loaded micelles were five times greater than that of the paclitaxel solution. In general, PF127-CS/PF127-cysteine/NaC micelles were proven to be a potential oral drug delivery system for paclitaxel.

  20. Biodegradable polymeric micelle-encapsulated quercetin suppresses tumor growth and metastasis in both transgenic zebrafish and mouse models (United States)

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


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

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

    Directory of Open Access Journals (Sweden)

    J. Varshosaz


    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.

  2. 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: [Yantai University, School of Pharmacy (China); Li, Youxin, E-mail: [Jilin University, College of Life Science (China)


    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.

  3. Characteristic of core materials in polymeric micelles effect on their micellar properties studied by experimental and dpd simulation methods. (United States)

    Cheng, Furong; Guan, Xuewa; Cao, Huan; Su, Ting; Cao, Jun; Chen, Yuanwei; Cai, Mengtan; He, Bin; Gu, Zhongwei; Luo, Xianglin


    Polymeric micelles are one important class of nanoparticles for anticancer drug delivery, but the impact of hydrophobic segments on drug encapsulation and release is unclear, which deters the rationalization of drug encapsulation into polymeric micelles. This paper focused on studying the correlation between the characteristics of hydrophobic segments and encapsulation of structurally different drugs (DOX and β-carotene). Poly(ϵ-caprolactone) (PCL) or poly(l-lactide) (PLLA) were used as hydrophobic segments to synthesize micelle-forming amphiphilic block copolymers with the hydrophilic methoxy-poly(ethylene glycol) (mPEG). Both blank and drug loaded micelles were spherical in shape with sizes lower than 50 nm. PCL-based micelles exhibited higher drug loading capacity than their PLLA-based counterparts. Higher encapsulation efficiency of β-carotene was achieved compared with DOX. In addition, both doxorubicin and β-carotene were released much faster from PCL-based polymeric micelles. Dissipative particle dynamics (DPD) simulation revealed that the two drugs tended to aggregate in the core of the PCL-based micelles but disperse in the core of PLLA based micelles. In vitro cytotoxicity investigation of DOX loaded micelles demonstrated that a faster drug release warranted a more efficient cancer-killing effect. This research could serve as a guideline for the rational design of polymeric micelles for drug delivery.

  4. Development and evaluation of N-naphthyl-N,O-succinyl chitosan micelles containing clotrimazole for oral candidiasis treatment. (United States)

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


    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.

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

    Institute of Scientific and Technical Information of China (English)

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


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

  6. 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


    as a model reaction. The micellar hydrodynamic radius results reflected, to some extent, the redistribution of surfactant and water after enzyme addition, and the correlation between surfactant formulation, water content (W0), micellar size, and enzyme activity. An adequate modification density of CB...... was found to be important for the reversed micelles to retain enough hydration capacity and achieve high enzyme activity. Compared with the results in AOT-based reversed micelles, CRL in this micellar system exhibited a different activity behavior versus W0. The optimal pH and temperature...... 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...

  7. Gold nanorod in reverse micelles: a fitting fusion to catapult lipase activity. (United States)

    Maiti, Subhabrata; Ghosh, Moumita; Das, Prasanta Kumar


    Lipase solubilized within gold nanorod doped CTAB reverse micelles exhibited remarkable improvement in its activity mainly due to the enhanced interfacial domain of newly developed self-assembled nanocomposites.

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

    Directory of Open Access Journals (Sweden)

    Mohannad Qurie


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

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

    Institute of Scientific and Technical Information of China (English)

    Ming Jiang


    @@ 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.

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

    Indian Academy of Sciences (India)

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


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

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

    CERN Document Server

    Lee, Kai Lun


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

  12. [Study on the backward extraction of cellulase in rhamnolipid reverse micelles]. (United States)

    Zhao, Yan-Ge; Yuan, Xing-Zhong; Huang, Hua-Jun; Cui, Kai-Long; Peng, Xin; Peng, Zi-Yuan; Zeng, Guang-Ming


    This paper studied the backward extraction of cellulase in RL/isooctane/n-hexanol reverse micelles system. Several key parameters influencing the backward extraction efficiency and activity recovery of cellulase were investigated, including stripping aqueous pH, stripping time, salt type and ionic strength, and addition of alcohols. The experiment results indicated that the optimal parameter values as follows: stripping aqueous pH 7.0, stripping time 30 min, 0.15 mol x L(-1) of KCl, dosage of n-butanol 2%. Under above optimum conditions, the backward extraction efficiency and activity recovery were up to 76.22% and 93.39%, respectively. The backward extraction of cellulase using reverse micelles based on biosurfactant RL performs well. Furthermore, RL has many advantages such as high biodegradability, low critical micelle concentration, etc. The application prospects of RL reverse micelles are extensive.

  13. 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: [Institute of Chemistry, St. Petersburg State University, Universitetskiy pr. 26, Petrodvoretz, St. Petersburg 198504 (Russian Federation)


    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.

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

    Institute of Scientific and Technical Information of China (English)

    GAO Jian; GE Wei; LI Jinghai


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


    Institute of Scientific and Technical Information of China (English)

    Pan He; Chang-wen Zhao; Chun-sheng Xiao; Zhao-hui Tang; Xue-si Chen


    Polyion complex (PIC) micelles were spontaneously formed in aqueous solutions through electrostatic interaction between two oppositely charged block copolymers,poly(N-isopropylacrylamide)-b-poly(L-glutamic acid) and poly(N-isopropylacrylamide)-b-poly(L-lysine).Their controlled synthesis was achieved via the ring opening polymerization of N-carboxyanhydrides (NCA),ε-benzyloxycarbonyl-L-lysine (Lys(Z)-NCA) or γ-benzyl-L-glutamate (BLG-NCA) with amino-terminated poly(N-isopropylacrylamide) macroinitiator and the subsequent deprotection reaction.The formation of PIC micelles was confirmed by dynamic light scattering and transmission electron microscopy.Turbidimetric characterization suggested that the formed PIC micelles had a concentration-dependent thermosensitivity and their phase transition behaviors could be easily adjusted either by the block length of coplymers or the concentration of micelles.

  16. Exploring Polymeric Micelles for Improved Delivery of Anticancer Agents: Recent Developments in Preclinical Studies

    Directory of Open Access Journals (Sweden)

    Wei Fan


    Full Text Available As versatile drug delivery systems, polymeric micelles have demonstrated particular strength in solubilizing hydrophobic anticancer drugs while eliminating the use of toxic organic solvents and surfactants. However, the true promise of polymeric micelles as drug carriers for cancer therapy resides in their potential ability to preferentially elevate drug exposure in the tumor and achieve enhanced anticancer efficacy, which still remains to be fully exploited. Here, we review various micellar constructs that exhibit the enhanced permeation and retention effect in the tumor, the targeting ligands that potentiate the anticancer efficacy of micellar drugs, and the polyplex micelle systems suitable for the delivery of plasmid DNA and small interference RNA. Together, these preclinical studies in animal models help us further explore polymeric micelles as emerging drug carriers for targeted cancer therapy.

  17. CD and 31P NMR studies of tachykinin and MSH neuropeptides in SDS and DPC micelles (United States)

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


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

  18. Neutral phospholipids stimulate Na,K-ATPase activity: a specific lipid-protein interaction. (United States)

    Haviv, Haim; Habeck, Michael; Kanai, Ryuta; Toyoshima, Chikashi; Karlish, Steven J D


    Membrane proteins interact with phospholipids either via an annular layer surrounding the transmembrane segments or by specific lipid-protein interactions. Although specifically bound phospholipids are observed in many crystal structures of membrane proteins, their roles are not well understood. Na,K-ATPase is highly dependent on acid phospholipids, especially phosphatidylserine, and previous work on purified detergent-soluble recombinant Na,K-ATPase showed that phosphatidylserine stabilizes and specifically interacts with the protein. Most recently the phosphatidylserine binding site has been located between transmembrane segments of αTM8-10 and the FXYD protein. This paper describes stimulation of Na,K-ATPase activity of the purified human α1β1 or α1β1FXYD1 complexes by neutral phospholipids, phosphatidylcholine, or phosphatidylethanolamine. In the presence of phosphatidylserine, soy phosphatidylcholine increases the Na,K-ATPase turnover rate from 5483 ± 144 to 7552 ± 105 (p phospholipids shows that the stimulatory effect is structurally selective for neutral phospholipids with polyunsaturated fatty acyl chains, especially dilinoleoyl phosphatidylcholine or phosphatidylethanolamine. By contrast to phosphatidylserine, phosphatidylcholine or phosphatidylethanolamine destabilizes the Na,K-ATPase. Structural selectivity for stimulation of Na,K-ATPase activity and destabilization by neutral phospholipids distinguish these effects from the stabilizing effects of phosphatidylserine and imply that the phospholipids bind at distinct sites. A re-examination of electron densities of shark Na,K-ATPase is consistent with two bound phospholipids located between transmembrane segments αTM8-10 and TMFXYD (site A) and between TM2, -4, -6, -and 9 (site B). Comparison of the phospholipid binding pockets in E2 and E1 conformations suggests a possible mechanism of stimulation of Na,K-ATPase activity by the neutral phospholipid.

  19. Multifunctional targeting micelle nanocarriers with both imaging and therapeutic potential for bladder cancer

    Directory of Open Access Journals (Sweden)

    Lin TY


    Full Text Available Tzu-yin Lin,1 Hongyong Zhang,1 Juntao Luo,2,5 Yuanpei Li,2 Tingjuan Gao,3 Primo N Lara Jr,1,4,6 Ralph de Vere White,4 Kit S Lam,1,2 Chong-Xian Pan,1,3,61Division of Hematology and Oncology, Department of Internal Medicine, 2Department of Biochemistry and Molecular Medicine, 3NSF Center for Biophotonics Science and Technology, School of Medicine, 4Department of Urology, University of California-Davis, Sacramento, CA, 5Department of Pharmacology, SUNY Upstate Medical University, Syracuse, NY, 6VA Northern California Health Care System, Mather, CA, USABackground: We previously developed a bladder cancer-specific ligand (PLZ4 that can specifically bind to both human and dog bladder cancer cells in vitro and in vivo. We have also developed a micelle nanocarrier drug-delivery system. Here, we assessed whether the targeting micelles decorated with PLZ4 on the surface could specifically target dog bladder cancer cells.Materials and methods: Micelle-building monomers (ie, telodendrimers were synthesized through conjugation of polyethylene glycol with a cholic acid cluster at one end and PLZ4 at the other, which then self-assembled in an aqueous solution to form micelles. Dog bladder cancer cell lines were used for in vitro and in vivo drug delivery studies.Results: Compared to nontargeting micelles, targeting PLZ4 micelles (23.2 ± 8.1 nm in diameter loaded with the imaging agent DiD and the chemotherapeutic drug paclitaxel or daunorubicin were more efficient in targeted drug delivery and more effective in cell killing in vitro. PLZ4 facilitated the uptake of micelles together with the cargo load into the target cells. We also developed an orthotopic invasive dog bladder cancer xenograft model in mice. In vivo studies with this model showed the targeting micelles were more efficient in targeted drug delivery than the free dye (14.3×; P < 0.01 and nontargeting micelles (1.5×; P < 0.05.Conclusion: Targeting micelles decorated with PLZ4 can selectively

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

    Directory of Open Access Journals (Sweden)

    Shi YN


    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

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

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


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

  2. Multimodality CT/SPECT Evaluation of Micelle Drug Carriers for Treatment of Breast Tumors (United States)


    TEM), dynamic light scattering (DLS), and NMR to examine morphology, size, and drug encapsulation . The in vitro efficacy of the micelles was seen in Figure 2, β-lap PEG-PLA micelles were core-shell in nature, possessing a PEG hydrated layer on the surface, all the while encapsulating ...hydroxypropyl-β- cyclodextrin (HPβ-CD). However, the clinical trials show that a large number of patients suffer from high levels of hemolysis and anemia

  3. Corrosion Performance of Carbon Steel in Simulated Pore Solution in the Presence of Micelles


    Hu, J; Koleva, D. A.; Wit, J.H.W. de; Kolev, H.; Breugel, K. van


    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 free and chloride-containing cement extracts. The electrochemical measurements (electrochemical impedance spectroscopy and potentiodynamic polarization) indicate that the presence of micelles alter...

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

    Institute of Scientific and Technical Information of China (English)


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

  5. Rheological properties of wormlike micelles formed in the sodium oleate/trisodium phosphate aqueous solution

    Institute of Scientific and Technical Information of China (English)

    Yong Qiang Ji; Wei Shan Wang; Gan Zuo Li; Li Qiang Zheng


    Aqueous solution of anionic surfactant,sodium oleate (NaOA),was studied by means of steady-state shear rheology and dynamic oscillatory technique.The system of NaOA/Na3PO4 showed high viscosity,strong viscoelasticity and good ability of countering Ca2+,Mg2+.The Maxwell model and Cole-Cole plot were applied to study the dynamic viscoelasticity of wormlike micelles.The microstructures of the wormlike micelles were characterized by FF-TEM.

  6. Multifunctional polymeric micelles for delivery of drugs and siRNA

    Directory of Open Access Journals (Sweden)

    Aditi M. Jhaveri


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

  7. Phospholipid homeostasis and lipotoxic cardiomyopathy: a matter of balance. (United States)

    Lim, Hui-Ying; Bodmer, Rolf


    Obesity has reached pandemic proportions globally and is often associated with lipotoxic heart diseases. In the obese state, caloric surplus is accommodated in the adipocytes as triglycerides. As the storage capacity of adipocytes is exceeded or malfunctioning, lipids begin to infiltrate and accumulate in non-adipose tissues, including the myocardium of the heart, leading to organ dysfunction. While the disruption of caloric homeostasis has been widely viewed as a principal mechanism in contributing to peripheral tissue steatosis and lipotoxicity, our recent studies in Drosophila have led to the novel finding that deregulation of phospholipid homeostasis may also significantly contribute to the pathogenesis of lipotoxic cardiomyopathy. Fly mutants that bear perturbations in phosphatidylethanolamine (PE) biosynthesis, such as the easily-shocked (eas) mutants defective in ethanolamine kinase, incurred aberrant activation of the sterol regulatory element binding protein (SREBP) pathway, thereby causing chronic lipogenesis and cardiac steatosis that culminates in the development of lipotoxic cardiomyopathy. Here, we describe the potential relationship between SREBP and other eas-associated phenotypes, such as neuronal excitability defects. We will further discuss the additional implications presented by our work toward the effects of altered lipid metabolism on cellular growth and/or proliferation in response to defective phospholipid homeostasis.

  8. Influence of silybin on biophysical properties of phospholipid bilayers

    Institute of Scientific and Technical Information of China (English)

    Olga WESO(L)OWSKA; Krystyna MICHALAK; Barbara (L)ANIA-PIETRZAK; Micha(l) KU(Z)D(Z)A(L); Kamila STA(N)CZAK; Daniela MOSI(A)DZ; Piotr DOBRYSZYCKI; Andrzej O(Z)YHAR; Ma(l)gorzata KOMOROWSKA; Andrzej B HENDRICH


    Aim: Silybin (silibinin)is major biologically active flavonolignan extracted from milk thistle (Sylibum marianum). Its biological activities include hepato-protection, anticancer properties, and antioxidant- and membrane-stabilizing functions. Al-though membranes are postulated to be one of the cellular targets for silybin, little is known about its interaction with phospholipid bilayers. Methods: In the present work, the interactions of silybin with phosphatidylcholine bilayers were studied in detail using fluorescence spectroscopy, microcalorimetry and electron spin resonance techniques. Results: The results showed that silybin interacted with the surface of lipid bilayers. It affected the generalized polarization of the fluores-cent probe Prodan, while not influencing the more deeplylocated Laurdan. Silybin lowered the main phospholipid phase transition temperature as judged by microcalorimetry, and caused the immobilization of spin probe Tempo-palmitate located on the surface of membranes. The mobility of spin probes 5-and 16-doxylstearic acid was not affected by silybin. Silybin-induced quenching of 1,6-diphe-nyl-1,3,5-hexatriene fluorescence indicated that some flavonoid molecules parti-tioned into the hydrophobic region of membranes, which did not change signifi-cantly the biophysical properties of the deeper membrane regions. Conclusion: Such a behavior of silybin in membranes is in accordance with its postulated biological functions and neglectable side effects of therapies using silybin.

  9. [Plasma lipoproteins as drug carriers. Effect of phospholipid formulations]. (United States)

    Torkhovskaia, T I; Ipatova, O M; Medvedeva, N V; Ivanov, V S; Ivanova, L I


    The extensive development of nanotechnologies in the last two decades has brought about new understanding of plasma lipoproteins (LP) as natural drug nanocarriers that escape interaction with immune and reticuloendothelial systems. Drugs bound to LP (especially LDL) can more actively penetrate into cells of many cancer and inflammation tissues with enhanced expression or/and dysregulation of B,E receptors or possibly scavenger SR-BI receptors. Relevant studies are focused on the development of new dosage forms by conjugating lipophilic drugs either with isolated plasma LP or with their model formulations, such as nanoemulsions, mimetics, lipid nanospheres, etc. Some authors include in these particles serum or recombinant apoproteins, peptides, and modified polymer products. As shown recently, protein-free lipid nanoemulsions in plasma take up free apoA and apoE. Complexes with various LP also form after direct administration of lypophilic drugs into blood especially those enclosed in phospholipid formulations, e.g. liposomes. Results of evaluation of some lipophilic dugs (mainly cytostatics, amphotericin B, cyclosporine A, etc.) are discussed. Original data are presented on the influence of phospholipid formulations on the distribution of doxorubicin and indomethacin between LP classes after in vitro incubation in plasma. On the whole, the review illustrates the importance of research on LP and phospholi pid forms as drug nanocarriers to be used to enhance effect of therapy.

  10. Metformin Decouples Phospholipid Metabolism in Breast Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Tim A D Smith

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

  11. Inositol depletion restores vesicle transport in yeast phospholipid flippase mutants. (United States)

    Yamagami, Kanako; Yamamoto, Takaharu; Sakai, Shota; Mioka, Tetsuo; Sano, Takamitsu; Igarashi, Yasuyuki; Tanaka, Kazuma


    In eukaryotic cells, type 4 P-type ATPases function as phospholipid flippases, which translocate phospholipids from the exoplasmic leaflet to the cytoplasmic leaflet of the lipid bilayer. Flippases function in the formation of transport vesicles, but the mechanism remains unknown. Here, we isolate an arrestin-related trafficking adaptor, ART5, as a multicopy suppressor of the growth and endocytic recycling defects of flippase mutants in budding yeast. Consistent with a previous report that Art5p downregulates the inositol transporter Itr1p by endocytosis, we found that flippase mutations were also suppressed by the disruption of ITR1, as well as by depletion of inositol from the culture medium. Interestingly, inositol depletion suppressed the defects in all five flippase mutants. Inositol depletion also partially restored the formation of secretory vesicles in a flippase mutant. Inositol depletion caused changes in lipid composition, including a decrease in phosphatidylinositol and an increase in phosphatidylserine. A reduction in phosphatidylinositol levels caused by partially depleting the phosphatidylinositol synthase Pis1p also suppressed a flippase mutation. These results suggest that inositol depletion changes the lipid composition of the endosomal/TGN membranes, which results in vesicle formation from these membranes in the absence of flippases.

  12. Cell separation in microcanal coated with electrically charged phospholipid polymers. (United States)

    Ito, Tomomi; Iwasaki, Yasuhiko; Narita, Tadashi; Akiyoshi, Kazunari; Ishihara, Kazuhiko


    To separate the cell population in whole blood using microcanal, the surface was covered with a polyion complex (PIC) composed of electrically charged phospholipid polymers. The phospholipids polymers were prepared by the polymerization of 2-methacryloyloxyethyl phosphorylcholine (MPC) and n-butyl methacrylate with 3-(methacryloyloxypropyl)-trimethyl ammonium iodide as the cationic unit or potassium 3-methacryloyloxypropyl sulfonate as the anionic unit. The PIC was formed at the solid-liquid interface, that is, first, the cationic polymer was coated on the substrate and an aqueous solution containing the anionic polymer with different concentrations was applied to the polymer-coated substrate. The formation of the PIC was followed using a quartz crystal microbalance (QCM), and the PIC surfaces were analyzed by both zeta-potential measurement and X-ray photoelectron spectroscopic measurement. The surface electrical potential on the PIC was controllable from +40 to -40 mV by increasing the amount of the adsorbed anionic polymer. The PIC surface was prepared in microcanal. The surface electrical potential was sequentially changed. When the whole blood was introduced into the microcanal, the cells adhered on the positively charged surface, but could not adhere to the negatively charged surface. Even when the cells adhere to the surface, the morphology of cells was maintained. This is due to MPC units at the surface, which show a good biocompatibility. These results indicated that the change in the surface electrical potential will be a useful method to separate the cells from whole blood.

  13. Spontaneous structural transition in phospholipid-inspired aromatic phosphopeptide nanostructures. (United States)

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


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

  14. [Construction of biotin-modified polymeric micelles for pancreatic cancer targeted photodynamic therapy]. (United States)

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


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

  15. Physical characterization and antioxidant activity of thymol solubilized Tween 80 micelles (United States)

    Deng, Ling-Li; Taxipalati, Maierhaba; Que, Fei; Zhang, Hui


    Attempts were made to solubilize thymol in Tween 80 micelle to study the solubilization mechanism of thymol and the effect of solubilization on its antioxidant activity. The maximum solubilized concentration of thymol in a 2.0% (w/v) Tween 80 micelle solution is 0.2 wt%. There was no significant difference in Z-average diameter between the empty micelles and thymol solubilized micelles. 1H NMR spectra indicated that 3-H and 4-H on the benzene ring of thymol interacted with the ester group between the hydrophilic head group and the hydrophobic tail group of Tween 80 by Van der Waals’ force. Ferric reducing antioxidant potential (FRAP) and cupric ion reducing antioxidant capacity (CUPRAC) assays showed that the reducing antioxidant activity of free thymol did not change after solubilized in Tween 80 micelles. Compared to free thymol, the solubilized thymol showed higher activities to scavenge DPPH (2,2-diphenyl-1-picrylhydrazyl) and hydroxyl radicals. The present study suggested a possible preparation of thymol-carrying micelles with enhanced antioxidant activities that could be applied in food beverages.

  16. New shell crosslinked micelles from dextran with hydrophobic end groups and their interaction with bioactive molecules. (United States)

    Mocanu, Georgeta; Nichifor, Marieta; Stanciu, Magdalena C


    Micelles formed in aqueous solution by dextran with hydrophobic (alkyl) end-groups were stabilized through divinyl sulfone crosslinking of the dextran shell. The efficacy of the crosslinking reaction was influenced by the divinyl sulfone amount, the pH and micelle concentration. Crosslinked micelles with a moderate crosslinking degree were further functionalized by attachment of 10 and 17 moles% N-(2-hydroxypropyl)-N,N-dimethyl-N-benzylammonium chloride groups along the dextran chain. The size and shape of both crosslinked micelles and their cationic derivatives were analyzed by DLS and TEM. The prepared micelles were able to bind anionic diclofenac (60-370 mg/g), hydrophobic anionic indometacin (70-120 mg/g), and hydrophobic alpha-tocopherol (170-220 mg/g) or ergocalciferol (90-110 mg/g) by hydrophobic or/and electrostatic forces. The release experiments and the antioxidant activity of bound alpha-tocopherol highlighted the potential of the new nano-sized micelles mainly as carriers for prolonged and controlled delivery of hydrophobic drugs.

  17. Activity and Conformation of Yeast Alcohol Dehydrogenase (YADH) Entrapped in Reverse Micelles. (United States)

    Das; Mozumdar; Maitra


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

  18. Dielectric relaxation spectroscopy shows a sparingly hydrated interface and low counterion mobility in triflate micelles. (United States)

    Lima, Filipe S; Chaimovich, Hernan; Cuccovia, Iolanda M; Buchner, Richard


    The properties of ionic micelles are affected by the nature of the counterion. Specific ion effects can be dramatic, inducing even shape and phase changes in micellar solutions, transitions apparently related to micellar hydration and counterion binding at the micellar interface. Thus, determining the hydration and dynamics of ions in micellar systems capable of undergoing such transitions is a crucial step in understanding shape and phase changes. For cationic micelles, such transitions are common with large organic anions as counterions. Interestingly, however, phase separation also occurs for dodecyltrimethylammonium triflate (DTATf) micelles in the presence of sodium triflate (NaTf). Specific ion effects for micellar solutions of dodecyltrimethylammonium chloride (DTAC), bromide (DTAB), methanesulfonate (DTAMs), and triflate (DTATf) were studied with dielectric relaxation spectroscopy (DRS), a technique capable of monitoring hydration and counterion dynamics of micellar aggregates. In comparison to DTAB, DTAC, and DTAMs, DTATf micelles were found to be considerably less hydrated and showed reduced counterion mobility at the micellar interface. The obtained DTATf and DTAMs data support the reported central role of the anion's -CF3 moiety with respect to the properties of DTATf micelles. The reduced hydration observed for DTATf micelles was rationalized in terms of the higher packing of this surfactant compared to that of other DTA-based systems. The decreased mobility of Tf(-) anions condensed at the DTATf interface strongly suggests the insertion of Tf(-) in the micellar interface, which is apparently driven by the strong hydrophobicity of -CF3.

  19. Complete regression of xenograft tumors using biodegradable mPEG-PLA-SN38 block copolymer micelles. (United States)

    Lu, Lu; Zheng, Yan; Weng, Shuqiang; Zhu, Wenwei; Chen, Jinhong; Zhang, Xiaomin; Lee, Robert J; Yu, Bo; Jia, Huliang; Qin, Lunxiu


    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.

  20. Development of lycopene micelle and lycopene chylomicron and a comparison of bioavailability (United States)

    Jyun Chen, Yi; Inbaraj, Baskaran Stephen; Shiau Pu, Yeong; Chen, Bing Huei


    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.

  1. Thermostability of Cromobacterium viscosum lipase in AOT/isooctane reverse micelle. (United States)

    Talukder, M M R; Zaman, M M; Hayashi, Y; Wu, J C; Kawanishi, T


    The thermostability of Cromobacterium viscosum lipase (EC entrapped in AOT (sodium bis-[2-ethylhexyl] sulfosuccinate) reverse micelles was increased by the addition of short-chain polyethylene glycol (PEG 400). Two different approaches were considered: (1) the determination of half-life time and (2) the mechanistic analysis of deactivation kinetics. The half-life of lipase entrapped in AOT/isooctane reverse micelles with PEG 400 at 60 degrees C was 28 h, ninefold higher than that in reverse micelles without PEG 400. The lipase entrapped in both reverse micellar systems followed a series-type deactivation mechanism involving two first-order steps. The deactivation constant for the first step at 60 degrees C in PEG containing reverse micelles was 0.055 h!1, 11-fold lower than that in reverse micelles without PEG, whereas it remained almost constant for the second step. The inactivation energy of the lipase entrapped in reverse micelles with and without PEG 400 was 88.12 and 21.97 kJ/mol, respectively.

  2. Binary-component micelle and vesicle: Free energy and asymmetric distributions of amphiphiles between vesicle monolayers

    Institute of Scientific and Technical Information of China (English)

    Zhang Qi-Yi; Xiang Xun


    The real-space two-dimensional self-consistent field theory (SCFT) is employed to study the free energies of micelles and vesicles constituted by binary amphiphilic diblock copolymer AB in homopolymer A.With an increasing volume fraction of copolymer AB,there are morphological transitions from circle micelles to oblate circle-like micelles,to a compound structure with inverted micelles in the inner center and micelles outer layer,and to vesicles.Special attention is paid to the role of the copolymer AB in controlling the free energies of the micelles and vesicles by examining the effect of the length ratio of A/B with the fixed whole chain length of the AB copolymer,the length effect of A or B block with the corresponding fixed length of B or A block,for one component of copolymer,and the effect of different amphiphile compositions for a binary-component copolymer system.The quantity η is provided to describe the asymmetric density distribution of amphiphiles between the inner and outer monolayers of vesicles,and to quantify the relative asymmetric extent of the density distribution between two species of copolymers in binary component vesicles.

  3. Magnetothermally responsive star-block copolymeric micelles for controlled drug delivery and enhanced thermo-chemotherapy. (United States)

    Deng, Li; Ren, Jie; Li, Jianbo; Leng, Junzhao; Qu, Yang; Lin, Chao; Shi, Donglu


    Magnetothermally responsive drug-loaded micelles were designed and prepared for cancer therapy. These specially designed micelles are composed of the thermo-responsive star-block copolymer poly(ε-caprolactone)-block-poly(2-(2-methoxyethoxy)ethyl methacrylate-co-oligo(ethylene glycol)methacrylate) and Mn, Zn doped ferrite magnetic nanoparticles (MZF-MNPs). The thermo-responses of 6sPCL-b-P(MEO2MA-co-OEGMA) copolymers were shown to be dependent on the MEO2MA to OEGMA ratio. The lower critical solution temperature (LCST) of the star-block copolymers was controlled at 43 °C by adjusting the feed molar ratios of MEO2MA/OEGMA at 92 : 8. With the anti-tumor drug doxorubicin (DOX) self-assembling into the carrier system, the thermo-responsive micelles exhibited excellent temperature-triggered drug release behavior. In vitro cytotoxicity results showed high biocompatibility of the polymer micelles. Efficient cellular proliferation inhibition by the drug-loaded micelles was found on the HepG2 cells under different treatments. The thermo-responsive polymer micelles are promising for controlled drug delivery in tumor therapy under an alternating magnetic field.

  4. Covalent attachment of mechanoresponsive luminescent micelles to glasses and polymers in aqueous conditions. (United States)

    Sagara, Yoshimitsu; Komatsu, Toru; Ueno, Tasuku; Hanaoka, Kenjiro; Kato, Takashi; Nagano, Tetsuo


    Covalent attachment of mechanoresponsive luminescent organic or organometallic compounds to other materials is a promising approach to develop a wide variety of mechanoresponsive luminescent materials. Here, we report covalently linkable mechanoresponsive micelles that change their photoluminescence from yellow to green in response to mechanical stimulation under aqueous conditions. These micelles are composed of a dumbbell-shaped amphiphilic pyrene derivative having amine groups at the peripheral positions of its dendrons. Using a well-established cross-linker, the micelles were covalently linked via their peripheral amine groups to the surface of glass beads, polylactic acid (PLA) beads, and living cells under aqueous conditions. Vortexing of glass beads bearing the micelles in a glass vial filled with water caused a photoluminescence color change from yellow to green. PLA beads bearing the micelles showed no change in photoluminescence color under the same conditions. We ascribe this result to the lower density and stiffness of the PLA beads, because the color of the PLA beads changed on vortexing in the presence of bare glass beads. HeLa cells and HL-60 cells bearing the micelles showed no obvious photoluminescence color change under vortexing. The structure, photophysical properties, and mechanism of photoluminescence color change of the micellar assemblies were examined.

  5. Molecular dynamics simulation and NMR investigation of the association of the β-blockers atenolol and propranolol with a chiral molecular micelle (United States)

    Morris, Kevin F.; Billiot, Eugene J.; Billiot, Fereshteh H.; Hoffman, Charlene B.; Gladis, Ashley A.; Lipkowitz, Kenny B.; Southerland, William M.; Fang, Yayin


    Molecular dynamics simulations and NMR spectroscopy were used to compare the binding of two β-blocker drugs to the chiral molecular micelle poly-(sodium undecyl-(L)-leucine-valine). The molecular micelle is used as a chiral selector in capillary electrophoresis. This study is part of a larger effort to understand the mechanism of chiral recognition in capillary electrophoresis by characterizing the molecular micelle binding of chiral compounds with different geometries and charges. Propranolol and atenolol were chosen because their structures are similar, but their chiral interactions with the molecular micelle are different. Molecular dynamics simulations showed both propranolol enantiomers inserted their aromatic rings into the molecular micelle core and that (S)-propranolol associated more strongly with the molecular micelle than (R)-propranolol. This difference was attributed to stronger molecular micelle hydrogen bonding interactions experienced by (S)-propranolol. Atenolol enantiomers were found to bind near the molecular micelle surface and to have similar molecular micelle binding free energies.

  6. Continuous Production of Structured Phospholipids in a Packed Red Reactor with Lipase from Thermomyces lanuginosa

    DEFF Research Database (Denmark)

    Vikbjerg, Anders Falk; Peng, Lifeng; Mu, Huiling;


    The possibilities of producing structured phospholipids by lipase-catalyzed acidolysis between soybean phospholipids and caprylic acid were examined in continuous packed bed enzyme reactors. Acidolysis reactions were performed in both a solvent system and a solvent-free system with the commercial...

  7. Combined effect of sesamin and soybean phospholipid on hepatic fatty acid metabolism in rats. (United States)

    Ide, Takashi


    We studied the combined effect of sesamin (1:1 mixture of sesamin and episesamine) and soybean phospholipid on lipid metabolism in rats. Male rats were fed diets supplemented with 0 or 2 g/kg sesamin, and containing 0 or 50 g/kg soybean phospholipid, for 19 days. Sesamin and soybean phospholipid decreased serum triacylglycerol concentrations and the combination of these compounds further decreased the parameter in an additive fashion. Soybean phospholipid but not sesamin reduced the hepatic concentration of triacylglycerol. The combination failed to cause a strong decrease in hepatic triacylglycerol concentration, presumably due to the up-regulation of Cd36 by sesamin. Combination of sesamin and soybean phospholipid decreased the activity and mRNA levels of hepatic lipogenic enzymes in an additive fashion. Sesamin strongly increased the parameters of hepatic fatty acid oxidation enzymes. Soybean phospholipid increased hepatic activity of 3-hydroxyacyl-CoA dehydrogenase although it failed to affect the activity of other enzymes involved in fatty acid oxidation. Sesamin strongly increased hepatic concentration of carnitine. Sesamin and soybean phospholipid combination further increased this parameter, accompanying a parallel increase in mRNA expression of carnitine transporter. These changes can account for the strong decrease in serum triacylglycerol in rats fed a diet containing both sesamin and soybean phospholipid.

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

    NARCIS (Netherlands)

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


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

  9. Brain-targeting study of stearic acid–grafted chitosan micelle drug-delivery system

    Directory of Open Access Journals (Sweden)

    Xie YT


    Full Text Available Yi-Ting Xie, Yong-Zhong Du, Hong Yuan, Fu-Qiang HuCollege of Pharmaceutical Sciences, Zhejiang University, Hangzhou, ChinaPurpose: Therapy for central nervous system disease is mainly restricted by the blood–brain barrier. A drug-delivery system is an effective approach to overcome this barrier. In this research, the potential of polymeric micelles for brain-targeting drug delivery was studied.Methods: Stearic acid–grafted chitosan (CS-SA was synthesized by hydrophobic modification of chitosan with stearic acid. The physicochemical characteristics of CS-SA micelles were investigated. bEnd.3 cells were chosen as model cells to evaluate the internalization ability and cytotoxicity of CS-SA micelles in vitro. Doxorubicin (DOX, as a model drug, was physically encapsulated in CS-SA micelles. The in vivo brain-targeting ability of CS-SA micelles was qualitatively and quantitatively studied by in vivo imaging and high-performance liquid chromatography analysis, respectively. The therapeutic effect of DOX-loaded micelles in vitro was performed on glioma C6 cells.Results: The critical micelle concentration of CS-SA micelles with 26.9% ± 1.08% amino substitute degree was 65 µg/mL. The diameter and surface potential of synthesized CS-SA micelles in aqueous solution was 22 ± 0.98 nm and 36.4 ± 0.71 mV, respectively. CS-SA micelles presented excellent cellular uptake ability on bEnd.3 cells, the IC50 of which was 237.6 ± 6.61 µg/mL. DOX-loaded micelles exhibited slow drug-release behavior, with a cumulative release up to 72% within 48 hours in vitro. The cytotoxicity of DOX-loaded CS-SA micelles against C6 was 2.664 ± 0.036 µg/mL, compared with 0.181 ± 0.066 µg/mL of DOX • HCl. In vivo imaging results indicated that CS-SA was able to transport rapidly across the blood–brain barrier and into the brain. A maximum DOX distribution in brain of 1.01%/g was observed 15 minutes after administration and maintained above 0.45%/g within 1 hour


    This report presents a comprehensive spectral analysis of common bacterial phospholipids using electrospray/mass spectrometry (ESI/MS) under both negative and positive ionization conditions. Phospholipids under positive ionization yield sodium-adduct molecular ions which are mos...

  11. Adsorption behavior of pH-dependent phytic acid micelles at the copper surface observed by Raman and electrochemistry (United States)

    Shen, Shu; Du, Juan; Guo, Xiao-yu; Wen, Ying; Yang, Hai-Feng


    As heated at 90 °C, phytic acid (PA) molecules in the solution self-organized to form the PA micelles. The size of PA micelles could be tuned by varying pH of the solutions. The adsorption behavior of the different micelles at the copper surface and their corrosion inhibition mechanisms in 0.5 M H2SO4 solution were studied by using electrochemical impedance spectroscopy (EIS), potentiodynamic polarization and surface-enhanced Raman scattering (SERS) spectroscopy. Raman studies showed that the bigger micelles anchoring on the copper surface via P27sbnd O28, P43sbnd O42 and P35sbnd O36 groups, while the smaller PA micelles formed at pH 9 adsorbed at the surface through P35sbnd O36 group. The electrochemical measurements demonstrated that the copper modified with the smaller micelles presented the best inhibition efficiency in 0.5 M H2SO4 solution.

  12. Structure of pure SDS and DTAB micelles in brine determined by small-angle neutron scattering (SANS)

    DEFF Research Database (Denmark)

    Bergström, M.; Pedersen, J.S.


    The geometrical structure of pure SDS and DTAB surfactant micelles in the absence of added salt as well as its dependence on the concentration of NaBr have been investigated at 40 degrees C using small-angle neutron scattering (SANS). In contrast to previous SANS measurements on the same systems we...... have analysed the scattering data in the entire regime of scattering vectors that are relevant for determining the structure of the micelles. Our obtained results for pure surfactant micelles, as well as those of mixed catanionic micelles presented in a recent study, show somewhat unexpectedly...... that ordinary surfactant micelles are shaped as circular or elongated bilayers (tablets). Both SDS and DTAB micelles appeared to be disk-like in pure D2O and the corresponding data were best fitted with a model for (monodisperse) oblate ellipsoids of revolution with half axes a=12.0 Angstrom, b=20.3 Angstrom...

  13. Investigation of thermo-sensitive amphiphilic micelles as drug carriers for chemotherapy in cholangiocarcinoma in vitro and in vivo. (United States)

    Wang, Xuefeng; Li, Songgang; Wan, Ziwei; Quan, Zhiwei; Tan, Qinggang


    Cholangiocarcinoma is an epithelial cancer of the bile ducts with poor prognosis and, in recent years, a rapidly increasing incidence. In this study, nano-sized thermo-sensitive micelles were investigated as drug carriers to improve chemotherapy in cholangiocarcinoma. Thermo-sensitive amphiphilic block copolymer, P-(N,N-isopropylacrylamide-co-N-hydroxymethylacrylamide)-b-caprolactone [P-(NIPAAm-co-NHMAAm)-b-PCL] with lower critical solution temperature (LCST) at about 38°C was synthesized. Doxorubicin (DOX)-loaded micelles were prepared by dialysis method. The micelles exhibited a sustained and temperature-dependent DOX release. Toxicity of the blank micelles for human cholangiocarcinoma (QBC939) cells was minimal both in vitro and in vivo. In contrast, the DOX-loaded micelles effectively inhibited proliferation and induced apoptosis of QBC939 cells in vitro (pthermo-sensitive amphiphilic micelles are a promising and effective drug carrier, and show potential for improving chemotherapy for cholangiocarcinoma.

  14. Theoretical Assessment of Fluorinated Phospholipids in the Design of Liposomal Drug-Delivery Systems

    DEFF Research Database (Denmark)

    Madsen, Jesper J.united st; Fristrup, Peter; Peters, Günther H.J.


    Fluorinated phospholipid analogues are investigated as potential substrates for phospholipase A(2) (PLA(2)) using classical molecular dynamics simulations and quantum mechanics/density functional theory calculations. The fluorinated phospholipid analogues are a-fluoro (HF-ProAEL) and alpha......,alpha-difluoro (F-2-ProAEL) conjugates of (R)-1-O-hexadecyl-2-palmitoyl-sn-glycero-3-phoshocholineglycerol (ProAEL). Our results provide a theoretical assessment of the potential usefulness of these fluorinated lipids in the rational design of liposomal drug-delivery systems. The a-fluorine-substituted phospholipid...... at a progressively faster rate; the more electronegative substituent at the a-position effectively lowers the energy barrier for hydrolysis. We conclude that the partially fluorinated phospholipid analogues facilitate rational design of liposomal vesicles of phospholipid mixtures with desirable physicochemical...

  15. Effect of long-term aluminum feeding on lipid/phospholipid profiles of rat brain myelin

    Directory of Open Access Journals (Sweden)

    Dave Kunjan R


    Full Text Available Abstract Effect of long-term (90–100 days exposure of rats to soluble salt of aluminum (AlCl3 on myelin lipid profile was examined. The long-term exposure to AlCl3 resulted in a 60 % decrease in the total phospholipid (TPL content while the cholesterol (CHL content increased by 55 %. Consequently the TPL / CHL molar ratio decreased significantly by 62 %. The phospholipid composition of the myelin membrane changed drastically; the proportion of practically all the phospholipid classes decreased by 32 to 60 % except for phosphatidylcholine (PC and phosphatidylethanolamine (PE. Of the latter two, proportion of PC was unchanged while PE increased in proportion by 47 %. Quantitatively, all phospholipid classes decreased by from 42 to 76% with no change in the PE content. However the membrane fluidity was not altered in Al-treated rats. Many of the changes we observe here show striking similarities with the reported phospholipid profiles of Alzheimer brains.

  16. Recent Advances in Phospholipids from Colostrum, Milk and Dairy By-Products (United States)

    Verardo, Vito; Gómez-Caravaca, Ana Maria; Arráez-Román, David; Hettinga, Kasper


    Milk is one of the most important foods for mammals, because it is the first form of feed providing energy, nutrients and immunological factors. In the last few years, milk lipids have attracted the attention of researchers due to the presence of several bioactive components in the lipid fraction. The lipid fraction of milk and dairy products contains several components of nutritional significance, such as ω-3 and ω-6 polyunsaturated fatty acids, CLA, short chain fatty acids, gangliosides and phospholipids. Prospective cohort evidence has shown that phospholipids play an important role in the human diet and reinforce the possible relationship between their consumption and prevention of several chronic diseases. Because of these potential benefits of phospholipids in the human diet, this review is focused on the recent advances in phospholipids from colostrum, milk and dairy by-products. Phospholipid composition, its main determination methods and the health activities of these compounds will be addressed. PMID:28106745

  17. Phospholipid Membrane Protection by Sugar Molecules during Dehydration—Insights into Molecular Mechanisms Using Scattering Techniques (United States)

    Garvey, Christopher J.; Lenné, Thomas; Koster, Karen L.; Kent, Ben; Bryant, Gary


    Scattering techniques have played a key role in our understanding of the structure and function of phospholipid membranes. These techniques have been applied widely to study how different molecules (e.g., cholesterol) can affect phospholipid membrane structure. However, there has been much less attention paid to the effects of molecules that remain in the aqueous phase. One important example is the role played by small solutes, particularly sugars, in protecting phospholipid membranes during drying or slow freezing. In this paper, we present new results and a general methodology, which illustrate how contrast variation small angle neutron scattering (SANS) and synchrotron-based X-ray scattering (small angle (SAXS) and wide angle (WAXS)) can be used to quantitatively understand the interactions between solutes and phospholipids. Specifically, we show the assignment of lipid phases with synchrotron SAXS and explain how SANS reveals the exclusion of sugars from the aqueous region in the particular example of hexagonal II phases formed by phospholipids. PMID:23584028

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

    Energy Technology Data Exchange (ETDEWEB)

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


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

  19. Recent Advances in Phospholipids from Colostrum, Milk and Dairy By-Products

    Directory of Open Access Journals (Sweden)

    Vito Verardo


    Full Text Available Milk is one of the most important foods for mammals, because it is the first form of feed providing energy, nutrients and immunological factors. In the last few years, milk lipids have attracted the attention of researchers due to the presence of several bioactive components in the lipid fraction. The lipid fraction of milk and dairy products contains several components of nutritional significance, such as ω-3 and ω-6 polyunsaturated fatty acids, CLA, short chain fatty acids, gangliosides and phospholipids. Prospective cohort evidence has shown that phospholipids play an important role in the human diet and reinforce the possible relationship between their consumption and prevention of several chronic diseases. Because of these potential benefits of phospholipids in the human diet, this review is focused on the recent advances in phospholipids from colostrum, milk and dairy by-products. Phospholipid composition, its main determination methods and the health activities of these compounds will be addressed.

  20. Evolution of phospholipid contents during the production of quark cheese from buttermilk. (United States)

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


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

  1. Study on Osmotic Pressure and Liquid-Liquid Equilibria for Micelle, Colloid and Microemulsion Systems by Yukawa Potential

    Institute of Scientific and Technical Information of China (English)

    FU,Dong(付东); LU,Jiu-Fang(陆九芳); WU,Wei(吴畏); Li,Yi-Gui(李以圭)


    An equation of state (EOS) was established to study the osmotic pressure and liquid-liquid equilibria for micelle,colloid and microemulsion systems. The Carnahan-Starling equation was used for the hard sphere repulsion. The Yukawa potential was used to describe both the attractive dispersion and the double-layer repulsion. By using the established EOS, the osmotic pressures for charged colloid, uncharged micelle, uncharged and weakly charged microemuslion, the phase equilibria for uncharged micelle and charged colloid systems were studied.

  2. Theranostic reduction-sensitive gemcitabine prodrug micelles for near-infrared imaging and pancreatic cancer therapy (United States)

    Han, Haijie; Wang, Haibo; Chen, Yangjun; Li, Zuhong; Wang, Yin; Jin, Qiao; Ji, Jian


    A biodegradable and reduction-cleavable gemcitabine (GEM) polymeric prodrug with in vivo near-infrared (NIR) imaging ability was reported. This theranostic GEM prodrug PEG-b-[PLA-co-PMAC-graft-(IR820-co-GEM)] was synthesized by ring-opening polymerization and ``click'' reaction. The as-prepared reduction-sensitive prodrug could self-assemble into prodrug micelles in aqueous solution confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). In vitro drug release studies showed that these prodrug micelles were able to release GEM in an intracellular-mimicking reductive environment. These prodrug micelles could be effectively internalized by BxPC-3 pancreatic cancer cells, which were observed by confocal laser scanning microscopy (CLSM). Meanwhile, a methyl thiazolyl tetrazolium (MTT) assay demonstrated that this prodrug exhibited high cytotoxicity against BxPC-3 cells. The in vivo whole-animal near-infrared (NIR) imaging results showed that these prodrug micelles could be effectively accumulated in tumor tissue and had a longer blood circulation time than IR820-COOH. The endogenous reduction-sensitive gemcitabine prodrug micelles with the in vivo NIR imaging ability might have great potential in image-guided pancreatic cancer therapy.A biodegradable and reduction-cleavable gemcitabine (GEM) polymeric prodrug with in vivo near-infrared (NIR) imaging ability was reported. This theranostic GEM prodrug PEG-b-[PLA-co-PMAC-graft-(IR820-co-GEM)] was synthesized by ring-opening polymerization and ``click'' reaction. The as-prepared reduction-sensitive prodrug could self-assemble into prodrug micelles in aqueous solution confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). In vitro drug release studies showed that these prodrug micelles were able to release GEM in an intracellular-mimicking reductive environment. These prodrug micelles could be effectively internalized by BxPC-3 pancreatic cancer cells, which

  3. Self-assembled micelles of amphiphilic poly(L-phenylalanine-b-poly(L-serine polypeptides for tumor-targeted delivery

    Directory of Open Access Journals (Sweden)

    Zhao ZM


    Full Text Available Ziming Zhao,1,2,* Yu Wang,1,2,* Jin Han,1,2 Keli Wang,1 Dan Yang,1,2 Yihua Yang,1,2 Qian Du,1,2 Yuanjian Song,3 Xiaoxing Yin1,2 1Department of Pharmacy, 2Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, 3Department of Basic Medical Sciences, Xuzhou Medical College, Xuzhou, People’s Republic of China *These authors contributed equally to this work Abstract: The aim of this work was to design, synthesize, and characterize self-assembled micelles based on polypeptides as a potential antitumor drug carrier. Amphiphilic poly(L-phenylalanine-b-poly(L-serine (PFS polypeptides were obtained through the polymerization of N-carboxyanhydride. As a novel hydrophilic segment, poly(L-serine was utilized to enhance tumor targeting due to a large demand of tumors for serine. PFS could self-assemble into micelles with an average diameter of 110–240 nm and a slightly negative charge. PFS polypeptides adopted random coil in pH 7.4 phosphate-buffered saline and could partly transform to a-helix induced by trifluoroethanol. PFS micelles with a low critical micelle concentration of 4.0 µg mL-1 were stable in pH 5–9 buffers and serum albumin solution. PFS micelles had a loading capacity of 3.8% for coumarin-6 and exhibited a sustained drug release. Coumarin-6 loaded rhodamine B isothiocyanate-labeled PFS micelles were incubated with Huh-7 tumor cells to study the correlation between drugs and carriers during endocytosis. The uptake of drugs was consistent with the micelles, illustrating that the intracellular transport of drugs highly depended on the micelles. PFS micelles diffused in whole cytoplasm while coumarin-6 assumed localized distribution, suggesting that the micelles could release the loaded drugs in particular areas. The internalization mechanism of PFS micelles was involved with clathrin-mediated endocytosis and macropinocytosis. Excess serine inhibited the uptake of PFS micelles, which demonstrated that serine receptors played

  4. Interaction between cationic and conventional nonionic surfactants in the mixed micelle and monolayer formed in aqueous medium

    Directory of Open Access Journals (Sweden)

    Nabel A. Negm


    Full Text Available Mixed micellization and surface properties of cationic and nonionic surfactants dimethyl decyl-, tetradecyl- and hexadecyl phosphineoxide mixtures are studied using conductivity and surface tension measurements. The models of Rubingh, Rosen, and Clint, are used to obtain the interaction parameter, minimum area per molecule, mixed micelle composition, free energies of mixing and activity coefficients. The micellar mole fractions were always higher than ideal values indicating high contributions of cationics in mixed micelles. Activity coefficients were less than unity indicating synergism in micelles. The negative free energies of mixing showed the stability of the surfactants in the mixed micelles.

  5. Synthesis of Bioconjugate Sesterterpenoids with Phospholipids and Polyunsaturated Fatty Acids

    Directory of Open Access Journals (Sweden)

    Ana Gil-Mesón


    Full Text Available A series of sesterterpenoid bioconjugates with phospholipids and polyunsaturated fatty acids (PUFAs have been synthesized for biological activity testing as antiproliferative agents in several cancer cell lines. Different substitution analogues of the original lipidic ether edelfosine (1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine are obtained varying the sesterterpenoid in position 1 or 2 of the glycerol or a phosphocholine or PUFA unit in position 3. Simple bioconjugates of sesterterpenoids and eicosapentaenoic acid (EPA have been obtained too. All synthetic derivatives were tested against the human tumour cell lines HeLa (cervix and MCF-7 (breast. Some compounds showed good IC50 (0.3 and 0.2 μM values against these cell lines.

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

    DEFF Research Database (Denmark)

    Khandelia, Himanshu; Loubet, Bastien; Olzynska, Agnieszka


    We claim that (1) cholesterol protects bilayers from disruption caused by lipid oxidation by sequestering conical shaped oxidized lipid species such as 1-palmitoyl-2-azelaoyl-sn-glycero-3-phosphocholine (PZPC) away from phospholipid, because cholesterol and the oxidized lipid have complementary...... shapes and (2) mixtures of cholesterol and oxidized lipids can self-assemble into bilayers much like lysolipid–cholesterol mixtures. The evidence for bilayer protection comes from molecular dynamics (MD) simulations and dynamic light scattering (DLS) measurements. Unimodal size distributions of extruded...... vesicles (LUVETs) made up of a mixture of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and PZPC containing high amounts of PZPC are only obtained when cholesterol is present in high concentrations. In simulations, bilayers containing high amounts of PZPC become porous, unless cholesterol is also present...

  7. Marine Omega-3 Phospholipids: Metabolism and Biological Activities

    Directory of Open Access Journals (Sweden)

    Nils Hoem


    Full Text Available The biological activities of omega-3 fatty acids (n-3 FAs have been under extensive study for several decades. However, not much attention has been paid to differences of dietary forms, such as triglycerides (TGs versus ethyl esters or phospholipids (PLs. New innovative marine raw materials, like krill and fish by-products, present n-3 FAs mainly in the PL form. With their increasing availability, new evidence has emerged on n-3 PL biological activities and differences to n-3 TGs. In this review, we describe the recently discovered nutritional properties of n-3 PLs on different parameters of metabolic syndrome and highlight their different metabolic bioavailability in comparison to other dietary forms of n-3 FAs.

  8. Antioxidant effect of astaxanthin on phospholipid peroxidation in human erythrocytes. (United States)

    Nakagawa, Kiyotaka; Kiko, Takehiro; Miyazawa, Taiki; Carpentero Burdeos, Gregor; Kimura, Fumiko; Satoh, Akira; Miyazawa, Teruo


    Phospholipid hydroperoxides (PLOOH) accumulate abnormally in the erythrocytes of dementia patients, and dietary xanthophylls (polar carotenoids such as astaxanthin) are hypothesised to prevent the accumulation. In the present study, we conducted a randomised, double-blind, placebo-controlled human trial to assess the efficacy of 12-week astaxanthin supplementation (6 or 12 mg/d) on both astaxanthin and PLOOH levels in the erythrocytes of thirty middle-aged and senior subjects. After 12 weeks of treatment, erythrocyte astaxanthin concentrations were higher in both the 6 and 12 mg astaxanthin groups than in the placebo group. In contrast, erythrocyte PLOOH concentrations were lower in the astaxanthin groups than in the placebo group. In the plasma, somewhat lower PLOOH levels were found after astaxanthin treatment. These results suggest that astaxanthin supplementation results in improved erythrocyte antioxidant status and decreased PLOOH levels, which may contribute to the prevention of dementia.

  9. Organization and function of anionic phospholipids in bacteria. (United States)

    Lin, Ti-Yu; Weibel, Douglas B


    In addition to playing a central role as a permeability barrier for controlling the diffusion of molecules and ions in and out of bacterial cells, phospholipid (PL) membranes regulate the spatial and temporal position and function of membrane proteins that play an essential role in a variety of cellular functions. Based on the very large number of membrane-associated proteins encoded in genomes, an understanding of the role of PLs may be central to understanding bacterial cell biology. This area of microbiology has received considerable attention over the past two decades, and the local enrichment of anionic PLs has emerged as a candidate mechanism for biomolecular organization in bacterial cells. In this review, we summarize the current understanding of anionic PLs in bacteria, including their biosynthesis, subcellular localization, and physiological relevance, discuss evidence and mechanisms for enriching anionic PLs in membranes, and conclude with an assessment of future directions for this area of bacterial biochemistry, biophysics, and cell biology.

  10. Computer simulations of phospholipid-membrane thermodynamic fluctuations

    CERN Document Server

    Pedersen, Ulf R; Schrøder, Thomas B; Dyre, Jeppe C


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

  11. Forms, Crosstalks, and the Role of Phospholipid Biosynthesis in Autophagy

    Directory of Open Access Journals (Sweden)

    Leanne Pereira


    Full Text Available Autophagy is a highly conserved cellular process occurring during periods of stress to ensure a cell's survival by recycling cytosolic constituents and making products that can be used in energy generation and other essential processes. Three major forms of autophagy exist according to the specific mechanism through which cytoplasmic material is transported to a lysosome. Chaperone-mediated autophagy is a highly selective form of autophagy that delivers specific proteins for lysosomal degradation. Microautophagy is a less selective form of autophagy that occurs through lysosomal membrane invaginations, forming tubes and directly engulfing cytoplasm. Finally, macroautophagy involves formation of new membrane bilayers (autophagosomes that engulf cytosolic material and deliver it to lysosomes. This review provides new insights on the crosstalks between different forms of autophagy and the significance of bilayer-forming phospholipid synthesis in autophagosomal membrane formation.

  12. Anti-phospholipid antibodies in patients with Plasmodium falciparum malaria

    DEFF Research Database (Denmark)

    Jakobsen, P H; Morris-Jones, S D; Hviid, L;


    Plasma levels of antibodies against phosphatidylinositol (PI), phosphatidylcholine (PC) and cardiolipin (CL) were measured by enzyme-linked immunosorbent assay (ELISA) in patients from malaria endemic area of Sudan and The Gambia. Some Sudanese adults produced IgM antibodies against all three types...... of phospholipids (PL) during an acute Plasmodium falciparum infection. The anti-PL antibody titre returned to preinfection levels in most of the donors 30 days after the disease episode. IgG titres against PI, PC and CL were low. In Gambian children with malaria, IgM antibody titres against PI and PC were...... significantly higher in those with severe malaria than in those with mild malaria. These results show that a proportion of malaria patients produce anti-PL antibodies during infection and that titres of these antibodies are associated with the severity of disease....

  13. Microscopic methods in analysis of submicron phospholipid dispersions

    Directory of Open Access Journals (Sweden)

    Płaczek Marcin


    Full Text Available Microscopy belongs to the group of tests, used in pharmaceutical technology, that despite the lapse of time and the development of new analytical methods, still remain irreplaceable for the characterization of dispersed drug dosage forms (e.g., suspensions and emulsions. To obtain complete description of a specific drug formulation, such as parenteral colloidal products, a combination of different microscopic techniques is sometimes required. Electron microscopy methods are the most useful ones; however, even such basic methods as optical microscopy may be helpful for determination of some properties of a sample. The publication explicates the most popular microscopical techniques used nowadays for characterization of the morphology of nanoparticles suspended in pharmaceutical formulations; ad vantages and disadvantages of these methods are also discussed. Parenteral submicron formulations containing lecithin or a particular phospholipid were chosen as examples.

  14. Packing properties 1-alkanols and alkanes in a phospholipid membrane

    DEFF Research Database (Denmark)

    Westh, Peter


    into the membrane, Vm(puremem), was positive for small (C4-C6) 1-alkanols while it was negative for larger alcohols and all alkanes. The magnitude of Vm(puremem) ranged from about +4 cm3/mol for alcohols with an alkyl chain about half the length of the fatty acids of DMPC, to -10 to -15 cm3/mol for the alkanes......We have used vibrating tube densitometry to investigate the packing properties of four alkanes and a homologous series of ten alcohols in fluid-phase membranes of dimyristoyl phosphatidylcholine (DMPC). It was found that the volume change of transferring these compounds from their pure states...... and long chain alcohols. On the basis of these observations, previously published information on the structure of the membrane-solute complexes and the free volume properties of (pure) phospholipid membranes, we suggest that two effects dominate the packing properties of hydrophobic solutes in DMPC. First...

  15. Biochemical synthesis of gold and zinc nanoparticles in reverse micelles (United States)

    Egorova, E. M.


    Gold and zinc nanoparticles were obtained in AOT reverse micelles in isooctane by reduction of the corresponding metal ions by the natural pigment quercetin (the biochemical synthesis technique). Gold and zinc ions were introduced into the micellar solution of quercetin in the form of aqueous solutions, HAuCl4 and [Zn(NH3)4]SO4, to the water to AOT molar ratios 1-3 and 3-4, respectively. The process of nanoparticle formation was investigated by spectrophotometry. Nanoparticle size and shape were determined by transmission electron microscopy. The data obtained allow to conclude that there are two steps in metal ion-quercetin interaction: (1) complex formation, and (2) complex dissociation with subsequent formation of nanoparticles and a second product, presumably oxidized quercetin. Gold nanoparticles were found to be of various shapes (spheres, hexahedrons, triangles, and cylinders) and sizes, mainly in the 10-20 nm range; zinc nanoparticles are chiefly spherical and ˜5 nm in size. In both cases, the nanoparticles are stable in the air in micellar solution over long periods of time (from a several months to a several years).

  16. Determination of critical micelle concentration with the rotating sample system. (United States)

    Kao, Linus T; Shetty, Gautam N; Gratzl, Miklós


    A novel experimental approach using the rotating sample system (RSS) is proposed here for the determination of the critical micelle concentration (CMC) of surfactants. The RSS has been conceived in our laboratory as a convection platform for physicochemical studies and analyses in microliter-sized sample drops. The scheme allows for vigorous rotation of the drop despite its small size through efficient air-liquid mechanical coupling. Thus, changes in surface properties of aqueous samples result in corresponding modulation of the hydrodynamic performance of the RSS, which can be utilized to investigate interfacial phenomena. In this work, we demonstrate that the RSS can be used to study the effects of surfactants on the surface and in the bulk of very small samples with hydrodynamic electrochemistry. Potassium ferrocyanide is employed here with cyclic voltammetry to probe the air-water interface of solutions containing Triton X-100. The CMC of this surfactant determined using this approach is 140 ppm, which agrees well with reported values obtained with conventional methods in much larger samples. The results also demonstrate that besides the CMC, variations in bulk rheological properties can also be investigated in very small specimens using the RSS with a simple method.

  17. Crystalline free energies of micelles of diblock copolymer solutions

    CERN Document Server

    D'Adamo, Giuseppe; 10.1063/1.3509391


    We report a characterization of the relative stability and structural behavior of various micellar crystals of an athermal model of AB-diblock copolymers in solution. We adopt a previously devel- oped coarse-graining representation of the chains which maps each copolymer on a soft dumbbell. Thanks to this strong reduction of degrees of freedom, we are able to investigate large aggregated systems, and for a specific length ratio of the blocks f = MA/(MA + MB) = 0.6, to locate the order-disorder transition of the system of micelles. Above the transition, mechanical and thermal properties are found to depend on the number of particles per lattice site in the simulation box, and the application of a recent methodology for multiple occupancy crystals (B.M. Mladek et al., Phys. Rev. Lett. 99, 235702 (2007)) is necessary to correctly define the equilibrium state. Within this scheme we have performed free energy calculations at two reduced density {\\rho}/{\\rho}\\ast = 4,5 and for several cubic structures as FCC,BCC,A1...

  18. Low Critical Micelle Concentration Discrepancy between Theory and Experiment. (United States)

    García Daza, Fabián A; Mackie, Allan D


    Experimental measurements for a variety of surfactants unexpectedly show that the critical micelle concentration (CMC) becomes constant with respect to increasing the size of the hydrophobic tail. This observation disagrees with theoretical models where it is expected to continue to decrease exponentially. Because of the lack of a satisfactory explanation for such a discrepancy from theory, we have studied these systems using a coarse-grained model within the single-chain mean field (SCMF) theory combined with relevant micellar kinetic effects. In particular, a microscopic model for poly(ethylene oxide) alkyl ether was applied to describe a series of nonionic gemini surfactants. When kinetic effects are used to correct the equilibrium CMC values from the SCMF scheme together with the loss of surfactants due to adsorption on the experimental recipient, it is possible to reproduce the correct order of magnitude of the experimental CMC results. Hence it appears that the experimental values disagree with the theoretical predictions because they are not true equilibrium values due to the fact that the time scales for these low CMC values become astronomically large.

  19. pH-sensitive micelles for targeted drug delivery prepared using a novel membrane contactor method. (United States)

    Laouini, Abdallah; Koutroumanis, Konstantinos P; Charcosset, Catherine; Georgiadou, Stella; Fessi, Hatem; Holdich, Richard G; Vladisavljević, Goran T


    A novel membrane contactor method was used to produce size-controlled poly(ethylene glycol)-b-polycaprolactone (PEG-PCL) copolymer micelles composed of diblock copolymers with different average molecular weights, Mn (9200 or 10,400 Da) and hydrophilic fractions, f (0.67 or 0.59). By injecting 570 L m(-2) h(-1) of the organic phase (a 1 mg mL(-1) solution of PEG-PCL in tetrahydrofuran) through a microengineered nickel membrane with a hexagonal pore array and 200 μm pore spacing into deionized water agitated at 700 rpm, the micelle size linearly increased from 92 nm for a 5-μm pore size to 165 nm for a 40-μm pore size. The micelle size was finely tuned by the agitation rate, transmembrane flux and aqueous to organic phase ratio. An encapsulation efficiency of 89% and a drug loading of ~75% (w/w) were achieved when a hydrophobic drug (vitamin E) was entrapped within the micelles, as determined by ultracentrifugation method. The drug-loaded micelles had a mean size of 146 ± 7 nm, a polydispersity index of 0.09 ± 0.01, and a ζ potential of -19.5 ± 0.2 mV. When drug-loaded micelles where stored for 50 h, a pH sensitive drug release was achieved and a maximum amount of vitamin E (23%) was released at the pH of 1.9. When a pH-sensitive hydrazone bond was incorporated between PEG and PCL blocks, no significant change in micelle size was observed at the same micellization conditions.

  20. Temperature and pressure based NMR studies of detergent micelle phase equilibria. (United States)

    Alvares, Rohan; Gupta, Shaan; Macdonald, Peter M; Prosser, R Scott


    Bulk thermodynamic and volumetric parameters (ΔGmic°, ΔHmic°, ΔSmic°, ΔCp,mic°, ΔVmic°, and Δκmic°) associated with the monomer–micelle equilibrium, were directly determined for a variety of common detergents [sodium n-dodecyl sulfate (SDS), n-dodecyl phosphocholine (DPC), n-dodecyl-β-d-maltoside (DDM), and 7-cyclohexyl-1-heptyl phosphocholine (CyF)] via 1H NMR spectroscopy. For each temperature and pressure point, the critical micelle concentration (cmc) was obtained from a single 1H NMR spectrum at a single intermediate concentration by referencing the observed chemical shift to those of pure monomer and pure micellar phases. This permitted rapid measurements of the cmc over a range of temperatures and pressures. In all cases, micelle formation was strongly entropically favored, while enthalpy changes were all positive, with the exception of SDS, which exhibited a modestly negative enthalpy of micellization. Heat capacity changes were also characteristically negative, while partial molar volume changes were uniformly positive, as expected for an aggregation process dictated by hydrophobic effects. Isothermal compressibility changes were found to be consistent with previous measurements using other techniques. Thermodynamic measurements were also related to spectroscopic studies of topology and micelle structure. For example, paramagnetic effects resulting from the addition of dioxygen provided microscopic topological details concerning the hydrophobicity gradient along the detergent chains within their respective micelles as detected by 1H NMR. In a second example, combined 13C and 1H NMR chemical shift changes arising from application of high pressure, or upon micellization, of CyF provided site-specific details regarding micelle topology. In this fashion, bulk thermodynamics could be related to microscopic topological details within the detergent micelle.

  1. Development of casein microgels from cross-linking of casein micelles by genipin. (United States)

    Silva, Naaman F Nogueira; Saint-Jalmes, Arnaud; de Carvalho, Antônio F; Gaucheron, Frédéric


    Casein micelles are porous colloidal particles, constituted of casein molecules, water, and minerals. The vulnerability of the supramolecular structure of casein micelles face to changes in the environmental conditions restrains their applications in other domains besides food. Thus, redesigning casein micelles is a challenge to create new functionalities for these biosourced particles. The objective of this work was to create stable casein microgels from casein micelles using a natural cross-linker, named genipin. Suspensions of purified casein micelles (25 g L(-1)) were mixed with genipin solutions to have final concentrations of 5, 10, and 20 mM genipin. Covalently linked casein microgels were formed via cross-linking of lysyl and arginyl residues of casein molecules. The reacted products exhibited blue color. The cross-linking reaction induced gradual changes on the colloidal properties of the particles. The casein microgels were smaller and more negatively charged and presented smoother surfaces than casein micelles. These results were explained based on the cross-linking of free NH2 present in an external layer of κ-casein. Light scattering and rheological measurements showed that the reaction between genipin and casein molecules was intramicellar, as one single population of particles was observed and the values of viscosity (and, consequently, the volume fraction of the particles) were reduced. Contrary to the casein micelles, the casein microgels were resistant to the presence of dissociating agents, e.g., citrate (calcium chelating) and urea, but swelled as a consequence of internal electrostatic repulsion and the disruption of hydrophobic interactions between protein chains. The casein microgels did not dissociate at the air-solution interface and formed solid-like interfaces rather than a viscoelastic gel. The potential use of casein microgels as adaptable nanocarriers is proposed in the article.

  2. 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.

  3. Essential phospholipids in fatty liver: a scientific update

    Directory of Open Access Journals (Sweden)

    Gundermann KJ


    Full Text Available Karl-Josef Gundermann,1 Simon Gundermann,2 Marek Drozdzik,1 VG Mohan Prasad3 1Department of Pharmacology, Pomeranian Medical University, Szczecin, Poland; 2Department of Radiology, Hospital Hohenlind, Cologne, Germany; 3VGM Hospital Institute of Gastroenterology, Coimbatore, India Aim: Although essential phospholipids (EPL from soybean are often used in membrane-associated disorders and diseases, their high quality of purification and effects on prevalent liver diseases, especially on fatty liver diseases (FLDs of different origin, are still widely unknown and a matter of continuous active research. The aim of this article is to review, discuss, and summarize the available results of EPL in the treatment of FLD. Methods: Database research was carried out on Medline, Embase, Cochrane Library, country-specific journals, and follow-up literature citations for relevant hepatogastroenterological articles published between 1988 and 2014. We searched for and reviewed only those papers that indicated minimum extraction amount of 72% (3-sn-phosphatidylcholine from soybean as being necessary to treat patients with a considerable amount of 1,2-dilinoleoylphosphatidylcholine as a key component in EPL. Results: EPL has a well-established mode of action, therapeutic effectiveness, and lack of toxicity, which ensures clinically relevant efficacy-to-safety ratio. It influences membrane-dependent cellular functions and shows anti-inflammatory, antioxidant, antifibrogenic, antiapoptotic, membrane-protective, and lipid-regulating effects. Due to its positive effects on membrane composition and functions, it accelerates the improvement or normalization of subjective symptoms; pathological, clinical, and biochemical findings; hepatic imaging; and liver histology. It is justified to administer EPL together with other therapeutic measurements in the liver. Conclusion: Pharmacological and clinical results confirm the efficacy of EPL in the treatment of FLD. Keywords

  4. Identification of unusual phospholipid fatty acyl compositions of Acanthamoeba castellanii.

    Directory of Open Access Journals (Sweden)

    Marta Palusinska-Szysz

    Full Text Available Acanthamoeba are opportunistic protozoan pathogens that may lead to sight-threatening keratitis and fatal granulomatous encephalitis. The successful prognosis requires early diagnosis and differentiation of pathogenic Acanthamoeba followed by aggressive treatment regimen. The plasma membrane of Acanthamoeba consists of 25% phospholipids (PL. The presence of C20 and, recently reported, 28- and 30-carbon fatty acyl residues is characteristic of amoeba PL. A detailed knowledge about this unusual PL composition could help to differentiate Acanthamoeba from other parasites, e.g. bacteria and develop more efficient treatment strategies. Therefore, the detailed PL composition of Acanthamoeba castellanii was investigated by 31P nuclear magnetic resonance spectroscopy, thin-layer chromatography, gas chromatography, high performance liquid chromatography and liquid chromatography-mass spectrometry. Normal and reversed phase liquid chromatography coupled with mass spectrometric detection was used for detailed characterization of the fatty acyl composition of each detected PL. The most abundant fatty acyl residues in each PL class were octadecanoyl (18∶0, octadecenoyl (18∶1 Δ9 and hexadecanoyl (16∶0. However, some selected PLs contained also very long fatty acyl chains: the presence of 28- and 30-carbon fatty acyl residues was confirmed in phosphatidylethanolamine (PE, phosphatidylserine, phosphatidic acid and cardiolipin. The majority of these fatty acyl residues were also identified in PE that resulted in the following composition: 28∶1/20∶2, 30∶2/18∶1, 28∶0/20∶2, 30∶2/20∶4 and 30∶3/20∶3. The PL of amoebae are significantly different in comparison to other cells: we describe here for the first time unusual, very long chain fatty acids with Δ5-unsaturation (30∶35,21,24 and 30∶221,24 localized exclusively in specific phospholipid classes of A. castellanii protozoa that could serve as specific biomarkers for the presence of

  5. Identification of unusual phospholipid fatty acyl compositions of Acanthamoeba castellanii. (United States)

    Palusinska-Szysz, Marta; Kania, Magdalena; Turska-Szewczuk, Anna; Danikiewicz, Witold; Russa, Ryszard; Fuchs, Beate


    Acanthamoeba are opportunistic protozoan pathogens that may lead to sight-threatening keratitis and fatal granulomatous encephalitis. The successful prognosis requires early diagnosis and differentiation of pathogenic Acanthamoeba followed by aggressive treatment regimen. The plasma membrane of Acanthamoeba consists of 25% phospholipids (PL). The presence of C20 and, recently reported, 28- and 30-carbon fatty acyl residues is characteristic of amoeba PL. A detailed knowledge about this unusual PL composition could help to differentiate Acanthamoeba from other parasites, e.g. bacteria and develop more efficient treatment strategies. Therefore, the detailed PL composition of Acanthamoeba castellanii was investigated by 31P nuclear magnetic resonance spectroscopy, thin-layer chromatography, gas chromatography, high performance liquid chromatography and liquid chromatography-mass spectrometry. Normal and reversed phase liquid chromatography coupled with mass spectrometric detection was used for detailed characterization of the fatty acyl composition of each detected PL. The most abundant fatty acyl residues in each PL class were octadecanoyl (18∶0), octadecenoyl (18∶1 Δ9) and hexadecanoyl (16∶0). However, some selected PLs contained also very long fatty acyl chains: the presence of 28- and 30-carbon fatty acyl residues was confirmed in phosphatidylethanolamine (PE), phosphatidylserine, phosphatidic acid and cardiolipin. The majority of these fatty acyl residues were also identified in PE that resulted in the following composition: 28∶1/20∶2, 30∶2/18∶1, 28∶0/20∶2, 30∶2/20∶4 and 30∶3/20∶3. The PL of amoebae are significantly different in comparison to other cells: we describe here for the first time unusual, very long chain fatty acids with Δ5-unsaturation (30∶35,21,24) and 30∶221,24 localized exclusively in specific phospholipid classes of A. castellanii protozoa that could serve as specific biomarkers for the presence of these

  6. Optimization of the Electroformation of Giant Unilamellar Vesicles (GUVs) with Unsaturated Phospholipids. (United States)

    Breton, Marie; Amirkavei, Mooud; Mir, Lluis M


    Giant unilamellar vesicles (GUV) are widely used cell membrane models. GUVs have a cell-like diameter and contain the same phospholipids that constitute cell membranes. The most frequently used protocol to obtain these vesicles is termed electroformation, since key steps of this protocol consist in the application of an electric field to a phospholipid deposit. The potential oxidation of unsaturated phospholipids due to the application of an electric field has not yet been considered even though the presence of oxidized lipids in the membrane of GUVs could impact their permeability and their mechanical properties. Thanks to mass spectrometry analyses, we demonstrated that the electroformation technique can cause the oxidation of polyunsaturated phospholipids constituting the vesicles. Then, using flow cytometry, we showed that the amplitude and the duration of the electric field impact the number and the size of the vesicles. According to our results, the oxidation level of the phospholipids increases with their level of unsaturation as well as with the amplitude and the duration of the electric field. However, when the level of lipid oxidation exceeds 25 %, the diameter of the vesicles is decreased and when the level of lipid oxidation reaches 40 %, the vesicles burst or reorganize and their rate of production is reduced. In conclusion, the classical electroformation method should always be optimized, as a function of the phospholipid used, especially for producing giant liposomes of polyunsaturated phospholipids to be used as a cell membrane model.

  7. Thrombin generation and procoagulant phospholipids in patients with essential thrombocythemia and reactive thrombocytosis. (United States)

    Mignon, I; Grand, F; Boyer, F; Hunault-Berger, M; Hamel, J F; Macchi, L


    Thrombocytosis is a commonly encountered clinical scenario and can be either a secondary process (reactive thrombocytosis), or due to clonal disorder (i.e., essential thrombocythemia). This distinction is important as it carries implications for evaluation, prognosis and treatment. In this study we compared procoagulant potential in essential thrombocythemia and reactive thrombocytosis by measuring the thrombin generation and the level of circulating procoagulant phospholipids with functional tests. Twenty nine patients with essential thrombocythemia and 24 with reactive thrombocytosis were studied. Thrombin generation was determined by calibrated automated thrombography. Procoagulant phospholipids were detected by a chronometric standardised method (STA-Procoag-PPL). Patients with reactive thrombocytosis had a longer lag time, higher endogenous thrombin potential, peak of thrombin generation and velocity index than patients with essential thrombocythemia. The level of circulating procoagulant phospholipids was increased in patients with essential thrombocythemia as observed with the procoagulant phospholipids assay. Each parameter was analysed using ROC curves. Highest areas under the curve (AUC) were found for lag time and procoagulant phospholipids ratio (0.817 and 0.853, respectively), associated with high negative predictive value for ET (92.3% and 80%, respectively). In conclusion, patients with essential thrombocythemia and reactive thrombocytosis displayed significant differences in terms of thrombin generation and levels of procoagulant phospholipids. Among these parameters, lag time and procoagulant phospholipids ratio could help to differentiate between reactive thrombocytosis and essential thrombocythemia patients.

  8. Anticancer effects of saponin and saponin-phospholipid complex of Panax notoginseng grown in Vietnam

    Institute of Scientific and Technical Information of China (English)

    Thu Dang Kim; Hai Nguyen Thanh; Duong Nguyen Thuy; Loi Vu Duc; Thu Vu Thi; Hung Vu Manh; Patcharee Boonsiri; Tung Bui Thanh


    Objective: To evaluate the antitumor activity both in vitro and in vivo of saponin–phospholipid complex of Panax notoginseng. Methods: The in vitro cytotoxic effect of saponins extract and saponin–phospholipid complex against human lung cancer NCI-H460 and breast cancer cell lines BT474 was examined using MTS assay. For in vivo evaluation of antitumor potential, saponin and saponin–phospholipid complex were administered orally in rats induced mammary carcinogenesis by 7,12-dimethylbenz(a)anthracene, for 30 days. Results: Our data showed that saponin–phospholipid complex had stronger anticancer effect compared to saponin extract. The IC50 values of saponin–phospholipid complex and saponin extract for NCI-H460 cell lines were 28.47μg/mL and 47.97μg/mL, respectively and these values for BT474 cells were 53.18μg/mL and 86.24μg/mL, respectively. In vivo experiments, administration of saponin, saponin–phospholipid complex and paclitaxel (positive control) effectively suppressed 7,12-dimethylbenz(a) anthracene-induced breast cancer evidenced by a decrease in tumor volume, the reduction of lipid peroxidation level and increase in the body weight, and elevated the enzymatic antioxidant activities of su-peroxide dismutase, catalase, glutathione peroxidase in rat breast tissue. Conclusions: Our study suggests that saponin extract from Panax notoginseng and saponin–phospholipid complex have potential to prevent cancer, especially breast cancer.

  9. Static structure factor of polymerlike micelles: Overall dimension, flexibility, and local properties of lecithin reverse micelles in deuterated isooctane (United States)

    Jerke, Götz; Pedersen, Jan Skov; Egelhaaf, Stefan Ulrich; Schurtenberger, Peter


    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 concentrations in the dilute and semidilute regime cover approximately three decades of scattering vectors. The data have been analyzed using polymer renormalization-group theory and a nonlinear least-squares fitting procedure based upon a numerical expression for the single chain scattering function of a wormlike chain with excluded-volume effects. Furthermore, the influence of interaction effects on the static structure factor have been successfully examined within a modified random-phase approximation. Additional information on the local scale has been extracted by applying indirect Fourier transformation and square-root deconvolution techniques. We demonstrate that we can determine structural properties such as the micellar cross-section profile and flexibility as well as quantitatively incorporate the influence of micellar growth and excluded-volume effects on S(q,c).

  10. Flip-flop of phospholipids in proteoliposomes reconstituted from detergent extract of chloroplast membranes: kinetics and phospholipid specificity.

    Directory of Open Access Journals (Sweden)

    Archita Rajasekharan

    Full Text Available Eukaryotic cells are compartmentalized into distinct sub-cellular organelles by lipid bilayers, which are known to be involved in numerous cellular processes. The wide repertoire of lipids, synthesized in the biogenic membranes like the endoplasmic reticulum and bacterial cytoplasmic membranes are initially localized in the cytosolic leaflet and some of these lipids have to be translocated to the exoplasmic leaflet for membrane biogenesis and uniform growth. It is known that phospholipid (PL translocation in biogenic membranes is mediated by specific membrane proteins which occur in a rapid, bi-directional fashion without metabolic energy requirement and with no specificity to PL head group. A recent study reported the existence of biogenic membrane flippases in plants and that the mechanism of plant membrane biogenesis was similar to that found in animals. In this study, we demonstrate for the first time ATP independent and ATP dependent flippase activity in chloroplast membranes of plants. For this, we generated proteoliposomes from Triton X-100 extract of intact chloroplast, envelope membrane and thylakoid isolated from spinach leaves and assayed for flippase activity using fluorescent labeled phospholipids. Half-life time of flipping was found to be 6 ± 1 min. We also show that: (a intact chloroplast and envelope membrane reconstituted proteoliposomes can flip fluorescent labeled analogs of phosphatidylcholine in ATP independent manner, (b envelope membrane and thylakoid reconstituted proteoliposomes can flip phosphatidylglycerol in ATP dependent manner, (c Biogenic membrane ATP independent PC flipping activity is protein mediated and (d the kinetics of PC translocation gets affected differently upon treatment with protease and protein modifying reagents.

  11. Biochemical characterization of the interactions between doxorubicin and lipidic GM1 micelles with or without paclitaxel loading (United States)

    Leonhard, Victoria; Alasino, Roxana V; Bianco, Ismael D; Garro, Ariel G; Heredia, Valeria; Beltramo, Dante M


    Doxorubicin (Dox) is an anthracycline anticancer drug with high water solubility, whose use is limited primarily due to significant side effects. In this study it is shown that Dox interacts with monosialoglycosphingolipid (GM1) ganglioside micelles primarily through hydrophobic interactions independent of pH and ionic strength. In addition, Dox can be incorporated even into GM1 micelles already containing highly hydrophobic paclitaxel (Ptx). However, it was not possible to incorporate Ptx into Dox-containing GM1 micelles, suggesting that Dox could be occupying a more external position in the micelles. This result is in agreement with a higher hydrolysis of Dox than of Ptx when micelles were incubated at alkaline pH. The loading of Dox into GM1 micelles was observed over a broad range of temperature (4°C–55°C). Furthermore, Dox-loaded micelles were stable in aqueous solutions exhibiting no aggregation or precipitation for up to 2 months when kept at 4°C–25°C and even after freeze–thawing cycles. Upon exposure to blood components, Dox-containing micelles were observed to interact with human serum albumin. However, the amount of human serum albumin that ended up being associated to the micelles was inversely related to the amount of Dox, suggesting that both could share their binding sites. In vitro studies on Hep2 cells showed that the cellular uptake and cytotoxic activity of Dox and Ptx from the micellar complexes were similar to those of the free form of these drugs, even when the micelle was covered with albumin. These results support the idea of the existence of different nano-domains in a single micelle and the fact that this micellar model could be used as a platform for loading and delivering hydrophobic and hydrophilic active pharmaceutical ingredients. PMID:26005348

  12. Synthesis of the Hemoglobin-Conjugated Polymer Micelles by Thiol Michael Addition Reactions. (United States)

    Qi, Yanxin; Li, Taihang; Wang, Yupeng; Wei, Xing; Li, Bin; Chen, Xuesi; Xie, Zhigang; Jing, Xiabin; Huang, Yubin


    Amphiphilic triblock copolymers mPEG-b-PMAC-b-PCL are synthesized using methoxyl poly(ethylene glycol), cyclic carbonic ester monomer including acryloyl group, and ε-caprolactone. Copolymers are self-assembled into core-shell micelles in aqueous solution. Thiolated hemoglobin (Hb) is conjugated with micelles sufficiently through thiol Michael addition reaction to form hemoglobin nanoparticles (HbNs) with 200 nm in diameter. The conjugation of Hb onto the micelle surface is further confirmed by X-ray photoelectron spectroscopy. Feeding ratio of copolymer micelles to Hb at 1:3 would lead to the highest hemoglobin loading efficiency 36.7 wt%. The UV results demonstrate that the gas transporting capacity of HbNs is well remained after Hb is conjugated with polymeric micelles. Furthermore, the obtained HbNs have no obvious detrimental effects on blood components in vitro. This system may thus have great potential as one of the candidates to be developed as oxygen carriers and provide a reference for the modification of protein drugs.

  13. Micelles assembled with carbocyanine dyes for theranostic near-infrared fluorescent cancer imaging and photothermal therapy. (United States)

    Yang, Hong; Mao, Huajian; Wan, Zhihui; Zhu, Aijun; Guo, Miao; Li, Yanli; Li, Xinming; Wan, Jiangling; Yang, Xiangliang; Shuai, Xintao; Chen, Huabing


    It is an emerging focus to explore a theranostic nanocarrier for simultaneous cancer imaging and therapy. Herein, we demonstrate a theranostic micelle system for cancer near infrared fluorescent (NIRF) imaging with enhanced signal to noise ratio and superior photothermal therapy. The copolymers consisting of monomethoxy poly(ethylene glycol) and alkylamine-grafted poly(L-aspartic acid) are assembled with carbocyanine dyes into theranostic micelles, which exhibit small size, high loading capacity, good stability, sustained release behavior, and enhanced cellular uptake. The micelles achieve the preferable biodistribution and long-term retention of carbocyanine dyes at tumor, which result in enhanced NIRF imaging by generating stable retention of NIRF signals at both hypervascular and hypovascular tumors during a long-term imaging period of up to 8 day, accompanying with negligible noise at normal tissues. The photostability of carbocyanine dye (Cypate) plays an important role for long-term cancer imaging with enhanced SNR. Moreover, the micelles exhibit severe photothermal damage on cancer cells via the destabilization of subcellular organelles upon photoirradiation, causing superior photothermal tumor regress. The micelles act as a powerful theranostic nanocarrier for simultaneous cancer imaging with high contrast and superior photothermal therapy.

  14. Free Energy of Scission for Sodium Laureth-1-Sulfate Wormlike Micelles. (United States)

    Vogtt, Karsten; Jiang, Hanqiu; Beaucage, Gregory; Weaver, Michael


    Wormlike micelles (WLMs) are nanoscale, self-assembled components of many products from shampoos to fracking fluids due to their viscoelasticity. Their rheological behavior is largely governed by the contour length of the micelles and the concomitant propensity of the micelles to overlap and entangle. The large contour lengths, on the order of micrometers, is the result of a delicate balance between the scission enthalpy of the wormlike micelles on the one hand and entropic factors such as the mixing entropy of dispersion, the ordering of water molecules and counterions, and the mobility of branch points on the other hand. The structure and contour length of wormlike micelles assembled from sodium laureth-1-sulfate was determined at various temperatures using small-angle neutron scattering. The results allow the calculation of the enthalpy and entropy as well as the free energy of scission and are employed to critically evaluate the common methods to determine micellar scission energy from mean-field theory. Interesting behavior is observed when comparing branched and unbranched WLMs that may reflect on mechanistic differences in chain scission.

  15. 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:


    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.

  16. Preparation of novel ferrocene-based shell cross-linked thermoresponsive hybrid micelles with antitumor efficacy. (United States)

    Wei, Hua; Quan, Chang-Yun; Chang, Cong; Zhang, Xian-Zheng; Zhuo, Ren-Xi


    The shell cross-linked (SCL) thermoresponsive hybrid poly(N-isopropylacrylamide-co-aminoethyl methacrylate)-b-polymethyl methacrylate (P(NIPAAm-co-AMA)-b-PMMA) micelle consisting of a cross-linked thermoresponsive hybrid shell and a hydrophobic core domain was fabricated via a two-step process: micellization of P(NIPAAm-co-AMA)-b-PMMA in aqueous solution followed by cross-linking of the hydrophilic shell layer via the amidation reaction between the amine groups of AMA units and the carboxylic acid functions of 1,1'-ferrocenedicarboxylic acid. The SCL micelle showed reversible dispersion/aggregation in response to the temperature cycles through the lower critical solution temperature (LCST) of the thermoresponsive hybrid shell at around 36 degrees C, observed by turbidity measurements and dynamic light scattering (DLS). Besides the usage as an inorganic difunctional cross-linker, the inorganic ferrocene segment further endowed the SCL hybrid micelle with the antitumor efficacy, namely, the resulting SCL micelle exhibited a remarkable cytotoxic effect for HeLa cells with a very low IC50. The results showed that the SCL hybrid micelle developed in this study could be potentially used as an antitumor agent, which is unique compared to the conventional tumor therapy by using the antitumor drug loaded in the micellar core.

  17. NMR characterization of membrane protein-detergent micelle solutions by use of microcoil equipment. (United States)

    Stanczak, Pawel; Horst, Reto; Serrano, Pedro; Wüthrich, Kurt


    Using microcoil NMR technology, the uniformly (2)H,(15)N-labeled integral membrane protein OmpX, and the phosphocholine derivative detergent Fos-10 (n-decylphosphocholine), we investigated solutions of mixed protein-detergent micelles to determine the influence of the detergent concentration on the NMR spectra of the protein. In a first step, we identified key parameters that influence the composition of the micelle solutions, which resulted in a new protocol for the preparation of well-defined concentrated protein solutions. This led to the observation that high-quality 2D [(15)N,(1)H]-transverse relaxation-optimized spectroscopy (TROSY) spectra of OmpX reconstituted in mixed micelles with Fos-10 were obtained only in a limited range of detergent concentrations. Outside of this range from about 90-180 mM, we observed a significant decrease of the average peak intensity. Relaxation-optimized NMR measurements of the rotational and translational diffusion coefficients of the OmpX/Fos-10 mixed micelles, D(r) and D(t), respectively, then showed that the stoichiometry and the effective hydrodynamic radius of the protein-containing micelles are not significantly affected by high Fos-10 concentrations and that the deterioration of NMR spectra is due to the increased viscosity at high detergent concentrations. The paper thus provides a basis for refined guidelines on the preparation of integral membrane proteins for structural studies.

  18. Effect of A Long Chain Carboxylate Acid on Sodium Dodecyl Sulfate Micelle Structure: A SANS Study (United States)

    Patriati, Arum; Giri Rachman Putra, Edy; Seok Seong, Baek


    The effect of a different hydrocarbon chain length of carboxylate acid, i.e. dodecanoic acid, CH3(CH)10COOH or lauric acid and hexadecanoic acid, CH3(CH2)14COOH or palmitic acid as a co-surfactant in the 0.3 M sodium dedecyl sulfate, SDS micellar solution has been studied using small angle neutron scattering (SANS). The present of lauric acid has induced the SDS structural micelles. The ellipsoid micelles structures changed significantly in length (major axis) from 22.6 Å to 37.1 Å at a fixed minor axis of 16.7 Å in the present of 0.005 M to 0.1 M lauric acid. Nevertheless, this effect did not occur in the present of palmitic acid with the same concentration range. The present of palmitic acid molecules performed insignificant effect on the SDS micelles growth where the major axis of the micelle was elongated from 22.9 Å to 25.3 Å only. It showed that the appropriate hydrocarbon chain length between surfactant and co-surfactant molecules emerged as one of the determining factors in forming a mixed micelles structure.

  19. Thermal deactivation kinetics of Pseudomonas fluorescens lipase entrapped in AOT/isooctane reverse micelles. (United States)

    Park, Kyung Min; Kwon, Chang Woo; Choi, Seung Jun; Son, Young-Hwan; Lim, Seokwon; Yoo, Yoonjung; Chang, Pahn-Shick


    Thermostability of the lipase (EC was found to be increased by the enzyme-entrapment in 50 mM AOT/isooctane reverse micelles. The half-life (15.75 h) of Pseudomonas fluorescens lipase entrapped in reverse micelles at 70 °C was 9.72- and 11.41-fold longer than those solubilized in a glycerol pool or in 10 mM phosphate buffer (pH 8.0), respectively. The enzyme deactivation model considering a two-step series-type was employed, and deactivation constants for the second step (k₂) at all temperatures were drastically decreased after the lipase was entrapped in reverse micelles. In particular, k₂ (0.0354 h⁻¹) at 70 °C in reverse micelles was 12.33- and 13.14-fold lower than in a glycerol pool or in the phosphate buffer, respectively. The deactivation energies (from k₁, k₂) for the lipase entrapped in the reverse micelles, solubilized in a glycerol pool, or in the aqueous buffer were 7.51, 26.35 kcal/mol, 5.93, 21.08 kcal/mol, and 5.53, 17.57 kcal/mol, respectively.

  20. Small angle neutron scattering study of doxorubicin–surfactant complexes encapsulated in block copolymer micelles

    Indian Academy of Sciences (India)

    Jayita Bhattacharjee; Gunjan Verma; V K Aswal; P A Hassan


    Self-assembling behaviour of block copolymers and their ability to evade the immune system through polyethylene oxide stealth makes it an attractive candidate for drug encapsulation. Micelles formed by polyethylene oxide–polypropylene oxide–polyethylene oxide triblock copolymers (PEO–PPO–PEO), pluronic P123, have been employed for encapsulating the anti-cancer drug doxorubicin hydrochloride. The binding affinity of doxorubicin within the micelle carrier is enhanced through complex formation of drug and anionic surfactant, aerosol OT (AOT). Electrostatic binding of doxorubicin with negatively charged surfactants leads to the formation of hydrophobic drug–surfactant complexes. Surfactant-induced partitioning of the anti-cancer drug into nonpolar solvents such as chloroform is investigated. SANS measurements were performed on pluronic P123 mi-celles in the presence of drug–surfactant complex. No significant changes in the structure of the micelles are observed upon drug encapsulation. This demonstrates that surfactant–drug complexes can be encapsulated in block copolymer micelles without disrupting the structure of aggregates.

  1. Oleyl-hyaluronan micelles loaded with upconverting nanoparticles for bio-imaging

    Energy Technology Data Exchange (ETDEWEB)

    Pospisilova, Martina, E-mail:; Mrazek, Jiri; Matuska, Vit; Kettou, Sofiane; Dusikova, Monika; Svozil, Vit; Nesporova, Kristina; Huerta-Angeles, Gloria; Vagnerova, Hana; Velebny, Vladimir [Contipro Biotech (Czech Republic)


    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.

  2. 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: [Mashhad University of Medical Sciences, Targeted Drug Delivery Research Center, School of Pharmacy (Iran, Islamic Republic of); Hadizadeh, Farzin, E-mail: [Mashhad University of Medical Sciences, Biotechnology Research Center, School of Pharmacy (Iran, Islamic Republic of)


    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.

  3. Direct Measurement of the Thermodynamics of Chiral Recognition in Bile Salt Micelles. (United States)

    Anderson, Shauna L; Rovnyak, David; Strein, Timothy G


    Isothermal titration calorimetry (ITC) is shown to be a sensitive reporter of bile salt micellization and chiral recognition. Detailed ITC characterization of bile micelle formation as well as the chiral recognition capabilities of sodium cholate (NaC), deoxycholate (NaDC), and taurodeoxycholate (NaTDC) micelle systems are reported. The ΔH(demic) of these bile salt micelle systems is directly observable and is strongly temperature-dependent, allowing also for the determination of ΔCp(demic). Using the pseudo-phase separation model, ΔG(demic) and TΔS(demic) were also calculated. Chirally selective guest-host binding of model racemic compounds 1,1'-bi-2-napthol (BN) and 1,1'-binaphthyl-2,2'-diylhydrogenphosphate (BNDHP) to bile salt micelles was then investigated. The S-isomer was shown to bind more tightly to the bile salt micelles in all cases. A model was developed that allows for the quantitative determination of the enthalpic difference in binding affinity that corresponds to chiral selectivity, which is on the order of 1 kJ mol(-1).

  4. Preparation and Characterization of a pH-Responsive Core Cross-linked Polymer Micelle

    Energy Technology Data Exchange (ETDEWEB)

    Kousaka, Shouta; Sugahara, Makoto; Endo, Tatsuya; Yusa, Shin-ichi, E-mail: [Department of Materials Science and Chemistry, Graduate School of Engineering, University of Hyogo, 2167 Shosha, Himeji, Hyogo 671-2280 (Japan)


    Poly(ethylene glycol)-b-poly(2-(diethylamino) ethyl methacrylate-co-2-cinnamoyl-oxyethyl acrylate) (PEG-b-P(DEA/CEA)) was prepared by reversible addition-fragmentation chain transfer (RAFT) controlled radical polymerization. pH-responsive association behaviour of PEG-b-P(DEA/CEA) in 0.1 M NaCl was characterized by dynamic light scattering (DLS). As solution pH is increased from an acidic pH, the hydrodynamic radius (R{sub h}) increases, indicative of the polymer micelle formation. The formation of a micelle was also supported by static light scattering (SLS) data. The cinnamoyl groups in the core of the polymer micelle undergo photodimerization, yielding cross-links between polymer chains. The core of the polymer micelle was fixed, which was confirmed by DLS, SLS, and small angle X-ray scattering (SAXS) techniques. When pH is decreased to 3, R{sub h} of the core cross-linked (CCL) polymer micelle slightly increases due to the protonation of the DEA unit in the cross-linked core. The reversible pH-induced swelling and shrinking behaviour can be observed.

  5. Electrical conductivity study on micelle formation of long-chain imidazolium ionic liquids in aqueous solution. (United States)

    Inoue, Tohru; Ebina, Hayato; Dong, Bin; Zheng, Liqiang


    Electrical conductivity was measured for aqueous solutions of long-chain imidazolium ionic liquids (IL), 1-alkyl-3-methylimidazolium bromides with C(12)-C(16) alkyl chains. The break points appeared in specific conductivity (kappa) vs concentration (c) plot indicates that the molecular aggregates, i.e., micelles, are formed in aqueous solutions of these IL species. The critical micelle concentration (cmc) determined from the kappa vs c plot is somewhat lower than those for typical cationic surfactants, alkyltrimethylammonium bromides with the same hydrocarbon chain length. The electrical conductivity data were analyzed according to the mixed electrolyte model of micellar solution, and the aggregation number, n, and the degree of counter ion binding, beta, were estimated. The n values of the present ILs are somewhat smaller than those reported for alkyltrimethylammonium bromides, which may be attributed to bulkiness of the cationic head group of the IL species. The thermodynamic parameters for micelle formation of the present ILs were estimated using the values of cmc and beta as a function of temperature. The contribution of entropy term to the micelle formation is superior to that of enthalpy term below about 30 degrees C, and it becomes opposite at higher temperature. This coincides with the picture drawn for the micelle formation of conventional ionic surfactants.

  6. Effect of the nature of phospholipids on the degree of their interaction with isobornylphenol antioxidants (United States)

    Marakulina, K. M.; Kramor, R. V.; Lukanina, Yu. K.; Plashchina, I. G.; Polyakov, A. V.; Fedorova, I. V.; Chukicheva, I. Yu.; Kutchin, A. V.; Shishkina, L. N.


    The parameters of complexation between natural phospholipids (lecithin, sphingomyelin, and cephalin) with antioxidants of a new class, isobornylphenols (IBPs), were determined by UV and IR spectroscopy. The self-organization of phospholipids (PLs) was studied depending on the structure of IBPs by dynamic light scattering. The nature of phospholipids and the structure of IBPs was found to produce a substantial effect both on the degree of complexation and on the size of PL aggregates in a nonpolar solvent. Based on the obtained data it was concluded that the structure of biological membranes mainly depends on the complexation of IBP with sphingomyelin.

  7. Glycerides and phospholipids of the cambial zone of the Siberian larch

    Energy Technology Data Exchange (ETDEWEB)

    Levin, E.D.; Rubchevskaya, L.P.; Vol, Ye.V.


    The composition is studied of glycerides and phospholipids of cambial zone of the Siberian larch and its annual dynamics. It is shown that monoglycerides, diglycerides and triglycerides are in the composition of the glycerides. The fatty acids of the glycerides are represented by a C12 to C24 series. The basic component of these compounds are unsaturated C18 acids. In the cambial zone there are phospholipids whose basic components are phosphatidylcholine and phosphatidylethanolamines. Their share of the weight in March exceeds 80 percent and in August is 69 percent of the weight of the phospholipids.

  8. Anticancer effects of saponin and saponin–phospholipid complex of Panax notoginseng grown in Vietnam


    Thu Dang Kim; Hai Nguyen Thanh; Duong Nguyen Thuy; Loi Vu Duc; Thu Vu Thi; Hung Vu Manh; Patcharee Boonsiri; Tung Bui Thanh


    Objective: To evaluate the antitumor activity both in vitro and in vivo of saponin–phospholipid complex of Panax notoginseng. Methods: The in vitro cytotoxic effect of saponins extract and saponin–phospholipid complex against human lung cancer NCI-H460 and breast cancer cell lines BT474 was examined using MTS assay. For in vivo evaluation of antitumor potential, saponin and saponin–phospholipid complex were administered orally in rats induced mammary carcinogenesis by 7,12-dimethylbenz(a)a...


    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. Membrane damage by bile salts: the protective function of phospholipids. (United States)

    Martin, G P; Marriott, C


    The direct toxicity of sodium deoxycholate (SDC) and lysophosphatidylcholine (LPC) to biological membranes was assessed by measurement of goldfish overturn time. When phosphatidylcholine (PC) was incorporated into the aqueous media, the toxicity of both SDC and LPC was reduced, as indicated by increased overturn time. Fish were also pretreated for various times in media containing (a) 1 mM SDC and (b) 1 mM SDC with 1 mM PC. Subsequent transfer to solution, 100 mg litre-1 quinalbarbitone sodium showed that reciprocal overturn times for fish treated using method (a) increased linearly with duration of pretreatment up to a limiting value, obtained after 20 min exposure; 40 min exposure to 1 mM SDC was directly toxic. Fish pretreated using regimen (b) survived longer when challenged with barbiturate, and the reciprocal overturn times were a linear function of time of pretreatment up to at least 40 min. PC also provided protection against membrane damage caused by the synthetic surfactant sodium dodecyl sulphate. Mixed micelle formation between PC and surfactant is thought to account for the protective effects. The results are of significance in the consideration of reflux hypothesis for the aetiology of gastric ulceration and also the possible formulation of drug delivery systems intended to enhance absorption whilst minimizing gastrointestinal damage.

  11. Complex coacervate core micelles with a lysozyme-modified corona. (United States)

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


    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.

  12. Biophysical studies of cholesterol in unsaturated phospholipid model membranes (United States)

    Williams, Justin Adam

    Cellular membranes contain a staggering diversity of lipids. The lipids are heterogeneously distributed to create regions, or domains, whose physical properties differ from the bulk membrane and play an essential role in modulating the function of resident proteins. Many basic questions pertaining to the formation of these lateral assemblies remain. This research employs model membranes of well-defined composition to focus on the potential role of polyunsaturated fatty acids (PUFAs) and their interaction with cholesterol (chol) in restructuring the membrane environment. Omega-3 (n-3) PUFAs are the main bioactive components of fish oil, whose consumption alleviates a variety of health problems by a molecular mechanism that is unclear. We hypothesize that the incorporation of PUFAs into membrane lipids and the effect they have on molecular organization may be, in part, responsible. Chol is a major constituent in the plasma membrane of mammals. It determines the arrangement and collective properties of neighboring lipids, driving the formation of domains via differential affinity for different lipids. The molecular organization of 1-[2H31]palmitoyl-2-eicosapentaenoylphosphatidylcholine (PEPC-d31) and 1-[2H31]palmitoyl-2-docosahexaenoylphosphatidylcholine (PDPC-d31) in membranes with sphingomyelin (SM) and chol (1:1:1 mol) was compared by solid-state 2H NMR spectroscopy. Eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids are the two major n-3 PUFAs found in fish oil, while PEPC-d31 and PDPC-d31 are phospholipids containing the respective PUFAs at the sn-2 position and a perdeuterated palmitic acid at the sn-1 position. Analysis of spectra recorded as a function of temperature indicates that in both cases, formation of PUFA-rich (less ordered) and SM-rich (more ordered) domains occurred. A surprisingly substantial proportion of PUFA was found to infiltrate the more ordered domain. There was almost twice as much DHA (65%) as EPA (30%). The implication is that n-3

  13. Pluronic-poly (acrylic acid)-cysteine/Pluronic L121 mixed micelles improve the oral bioavailability of paclitaxel. (United States)

    Zhao, Yanli; Li, Yanli; Ge, Jianjun; Li, Na; Li, Ling-Bing


    The aim of the study is to synthesize a thiolated Pluronic copolymer, Pluronic-poly (acrylic acid)-cysteine copolymer, to construct a mixed micelle system with the Pluronic-poly (acrylic acid)-cysteine copolymer and Pluronic L121 (PL121) and to evaluate the potential of these mixed micelles as an oral drug delivery system for paclitaxel. Compared with Pluronic-poly (acrylic acid)-cysteine micelles, drug-loading capacity of Pluronic-poly (acrylic acid)-cysteine/PL121 mixed micelles was increased from 0.4 to 2.87%. In vitro release test indicated that Pluronic-poly (acrylic acid)-cysteine/PL121 mixed micelles exhibited a pH sensitivity. The permeability of drug-loaded micelles in the intestinal tract was studied with an in situ perfusion method in rats. The presence of verapamil and Pluronic both improved the intestinal permeability of paclitaxel, which further certified the inhibition effect of thiolated Pluronic on P-gp. In pharmacokinetic study, the area under the plasma concentration-time curve (AUC0→∞) of paclitaxel-loaded mixed micelles was four times greater than that of the paclitaxel solution (p cysteine/PL121 micelles were proven to be a potential oral drug delivery system for paclitaxel.

  14. Photothermal Ablation of in Situ Renal Tumor by PEG-IR780-C13 Micelles and Near-Infrared Irradiation. (United States)

    Qiu, Xuefeng; Xu, Linfeng; Zhang, Yanting; Yuan, Ahu; Wang, Kaikai; Zhao, Xiaozhi; Wu, Jinhui; Guo, Hongqian; Hu, Yiqiao


    PEG-IR780-C13 micelles have been demonstrated to be a novel photothermal agent with tumor-targeting property. This study was designed to explore the feasibility of applying PEG-IR780-C13 micelles and near-infrared (NIR) irradiation for thermal ablation of renal tumor by using an in situ tumor model. In addition, the potential thermal injury to normal renal tissue was evaluated. PEG-IR780-C13 micelles were intended to accumulate in renal tumor after systemic delivery. In vitro results revealed that PEG-IR780-C13 micelles were uptaken by RENCA cells mainly through caveola-mediated endocytosis and mainly distributed in late endosomes and lysosomes. Upon NIR irradiation, PEG-IR780-C13 micelles generated heat effectively both in vitro and in vivo, exhibiting a promising photothermal therapeutic property. The photothermal effect of PEG-IR780-C13 micelles could effectively destroy RENCA cells in vitro and adequately inhibit growth of in situ renal tumor in vivo. Meanwhile, PEG-IR780-C13 micelles mediated photothermal therapy (PTT) resulting in only limited injury to normal renal tissue surrounding tumor sites. Our data indicated that PEG-IR780-C13 micelles mediating PTT could generate tumor-specific heat for destruction of renal tumor in a minimally invasive way, providing a novel strategy for thermal ablation of renal tumor.

  15. pH-Responsive Hyaluronic Acid-Based Mixed Micelles for the Hepatoma-Targeting Delivery of Doxorubicin

    Directory of Open Access Journals (Sweden)

    Jing-Liang Wu


    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.

  16. A small-angle neutron scattering study of sodium dodecyl sulfate-poly(propylene oxide) methacrylate mixed micelles. (United States)

    Bastiat, Guillaume; Grassl, Bruno; Borisov, Oleg; Lapp, Alain; François, Jeanne


    Mixed micelle of protonated or deuterated sodium dodecyl sulfate (SDS and SDSd25, respectively) and poly(propylene oxide) methacrylate (PPOMA) are studied by small-angle neutron scattering (SANS). In all the cases the scattering curves exhibit a peak whose position changes with the composition of the system. The main parameters which characterize mixed micelles, i.e., aggregation numbers of SDS and PPOMA, geometrical dimensions of the micelles and degree of ionisation are evaluated from the analysis of the SANS curves. The position q(max) of the correlation peak can be related to the average aggregation numbers of SDS-PPOMA and SDSd25-PPOMA mixed micelles. It is found that the aggregation number of SDS decreases upon increasing the weight ratio PPOMA/SDS (or SDSd25). The isotopic combination, which uses the "contrast effect" between the two micellar systems, has allowed us to determine the mixed micelle composition. Finally, the SANS curves were adjusted using the RMSA for the structure factor S(q) of charged spherical particles and the form factor P(q) of spherical core-shell particle. This analysis confirms the particular core-shell structure of the SDS-PPOMA mixed micelle, i.e., a SDS "core" micelle surrounded by the shell formed by PPOMA macromonomers. The structural parameters of mixed micelles obtained from the analysis of the SANS data are in good agreement with those determined previously by conductimetry and fluorescence studies.

  17. Thermo-responsive shell cross-linked PMMA-b-P(NIPAAm-co-NAS) micelles for drug delivery. (United States)

    Chang, Cong; Wei, Hua; Wu, De-Qun; Yang, Bin; Chen, Ni; Cheng, Si-Xue; Zhang, Xian-Zheng; Zhuo, Ren-Xi


    Thermo-responsive amphiphilic poly(methyl methacrylate)-b-poly(N-isopropylacrylamide-co-N-acryloxysuccinimide) (PMMA-b-P(NIPAAm-co-NAS)) block copolymer was synthesized by successive RAFT polymerizations. The uncross-linked micelles were facilely prepared by directly dissolving the block copolymer in an aqueous medium, and the shell cross-linked (SCL) micelles were further fabricated by the addition of ethylenediamine as a di-functional cross-linker into the micellar solution. Optical absorption measurements showed that the LCST of uncross-linked and cross-linked micelles was 31.0°C and 40.8°C, respectively. Transmission electron microscopy (TEM) showed that both uncross-linked and cross-linked micelles exhibited well-defined spherical shape in aqueous phase at room temperature, while the SCL micelles were able to retain the spherical shape with relatively smaller dimension even at 40°C due to the cross-linked structure. In vitro drug release study demonstrated a slower and more sustained drug release behavior from the SCL micelles at high temperature as compared with the release profile of uncross-linked micelles, indicating the great potential of SCL micelles developed herein as novel smart carriers for controlled drug release.

  18. Formation of reverse micelles in supercritical carbon dioxide and its thermodynamics

    Institute of Scientific and Technical Information of China (English)

    WEN Zhen; DANG Zhi; ZONG Minhua; ZHU Zhixin


    The solubilization behavior of methyl orange as a solvation probe in multiple systems composed of supercritical carbon dioxide,surfactants and co-solvents,is studied.It is coneluded that some surfactants,such as sodium bis-(2-ethylhexyl)sulfosuccinate(AOT)and isooctyl phenol polyethoxylate (TX-10),could form reverse micelles in supercritical carbon dioxide under the action of butanol.The formation of reverse micelles is a spontaneous process thermodynamically.Specifically for the nonionic surfactant TX-10,the formation of reverse micelles is dependent on the entropy increase in the system,while for the anionic surfactant AOT,the micellization is mainly dominated by the increase in enthalpy at higher temperatures,but by the increase in entropy at lower temperatures.

  19. Electrospun micelles/drug-loaded nanofibers for time-programmed multi-agent release. (United States)

    Yang, Guang; Wang, Jie; Li, Long; Ding, Shan; Zhou, Shaobing


    Combined therapy with drugs of different therapeutic effects is an effective way in the treatment of diseases and damaged tissues or organs. However, how to precisely control the release order, dose, and time of the drugs using vehicles is still a challenging task. In this work, for the first time, a study to develop a nanoscale multi-drug delivery system based on polymer micelle-enriched electrospun nanofibers is presented. The multi-drug delivery system is achieved, first, by the fabrication of hydrophobic curcumin encapsulated micelles assembled from biodegradable mPEG-PCL copolymer and, second, by the blending of the micelle powder with hydrophilic doxorubicin in polyvinyl alcohol solution, followed by simply electrospinning this combination. Due to the different domains of the two drugs within the nanofibers, the release behaviors show a time-programmed release, and can be temporally and spatially regulated. In vitro tumor cell inhibition assay indicates that the delivery system possesses great potential in cancer chemotherapy.

  20. Hyperbranched polycarbonate-based multimolecular micelle with enhanced stability and loading efficiency. (United States)

    Su, Wei; Luo, Xiao-Hua; Wang, Hua-Fen; Li, Lei; Feng, Jun; Zhang, Xian-Zheng; Zhuo, Ren-Xi


    We herein develop a facile catalyst-free method to prepare hyperbranched hydroxyl-enriched aliphatic polycarbonate according to SCROP strategy. PEG-attached multiarm hyperbranched copolymer HEHDO-star-mPEG was further designed. It was found that HEHDO-star-mPEG can self-assemble into supramolecular multimolecular micelles in water. HEHDO-star-mPEG micelle showed excellent stability with respect to micellar size upon dilution, and displayed good cell-biocompatibility. An anticancer drug of doxorubicin with hydrogen-bonding functionality was incorporated into obtained micelles to establish a drug delivery system model. A high drug-loading content as well as sustained release pattern for HEHDO-star-mPEG based delivery system was achieved.