Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Micelles”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed2006

Combining precision spin-probe partitioning with time-resolved fluorescence quenching to study micelles. Application to micelles of pure lysomyristoylphosphatidylcholine (LMPC) and LMPC mixed with sodium dodecyl sulfate.

Micelles of lysomyristoylphosphatidylcholine (LMPC) and mixed micelles of LMPC with anionic detergent sodium dodecyl sulfate (SDS) have been characterized by spin-probe-partitioning electron paramagnetic resonance (SPPEPR) and time-resolved fluorescence quenching (TRFQ) experiments. SPPEPR is a novel new method to study structure and dynamics in lipid assemblies successfully applied here for the first time to micelles. Several improvements to the computer program used to analyze SPPEPR spectra have been incorporated that increase the precision in the extracted parameters considerably from which micelle properties such as effective water concentration and microviscosity may be estimated. In addition, with this increased precision, it is shown that it is feasible to study the rate of transfer of a small spin probe between micelles and the surrounding aqueous phase by SPPEPR. The rate of transfer of the spin probe di-tert-butyl nitroxide (DTBN) and the activation energy of the transfer process in LMPC and LMPC-SDS micelles have been determined with high precision. The rate of transfer increases with temperature and SDS molar fraction in mixed micelles, while it remains constant with LMPC concentration in pure LMPC micelles. The activation energy of DTBN transfer in pure lysophospholipid micelles does not change with LMPC concentration while it decreases with the increasing molar fraction of SDS in mixed LMPC-SDS micelles. Both this decrease in activation energy and the increase in the rate of transfer are rationalized in terms of an increasing micelle surface area per molecule (decreasing compactness) as SDS molecules are added. This decreasing compactness as a function of SDS content is confirmed by TRFQ measurements showing an aggregation number that decreases from 122 molecules for pure LMPC micelles to 80 molecules for pure SDS micelles. The same increase in surface area per molecule is predicted to increase the effective water concentration in the polar shell of the micelles. This increase in hydration with SDS molar fraction is confirmed by measuring the effective water concentration in the polar shell of the micelles from the hyperfine spacing of DTBN. This work demonstrates the potential to design mixed lysophospholipid surfactant micelles with variable physicochemical properties. Well-defined micellar substrates, in terms of their physicochemical properties, may improve the studies of protein structure and enzyme kinetics.

Butanes↗
PubMed2003

Association of denatured whey proteins with casein micelles in heated reconstituted skim milk and its effect on casein micelle size.

When skim milk at pH 6.55 was heated (75 to 100 degrees C for up to 60 min), the casein micelle size, as monitored by photon correlation spectroscopy, was found to increase during the initial stages of heating and tended to plateau on prolonged heating. At any particular temperature, the casein micelle size increased with longer holding times, and, at any particular holding time, the casein micelle size increased with increasing temperature. The maximum increase in casein micelle size was about 30-35 nm. The changes in casein micelle size were poorly correlated with the level of whey protein denaturation. However, the changes in casein micelle size were highly correlated with the levels of denatured whey proteins that were associated with the casein micelles. The rate of association of the denatured whey proteins with the casein micelles was considerably slower than the rate of denaturation of the whey proteins. Removal of the whey proteins from the skim milk resulted in only small changes in casein micelle size during heating. Re-addition of beta-lactoglobulin to the whey-protein-depleted milk caused the casein micelle size to increase markedly on heat treatment. The changes in casein micelle size induced by the heat treatment of skim milk may be a consequence of the whey proteins associating with the casein micelles. However, these associated whey proteins would need to occlude a large amount of serum to account for the particle size changes. Separate experiments showed that the viscosity changes of heated milk and the estimated volume fraction changes were consistent with the particle size changes observed. Further studies are needed to determine whether the changes in size are due to the specific association of whey proteins with the micelles or whether a low level of aggregation of the casein micelles accompanies this association behaviour. Preliminary studies indicated lower levels of denatured whey proteins associated with the casein micelles and smaller changes in casein micelle size occurred as the pH of the milk was increased from pH 6.5 to pH 6.7.

Animals↗
PubMed1996

Preparation and characterization of the micelle-forming polymeric drug indomethacin-incorporated poly(ethylene oxide)-poly(beta-benzyl L-aspartate) block copolymer micelles.

To estimate the feasibility of novel containers for drugs, poly(ethylene oxide)-poly(beta-benzyl L-aspartate) (PEO-PBLA) micelles were prepared by dialysis against water using different solvents. The solvent selected is very important because it drastically affects the stability of polymeric micelles. The critical micelle concentration (cmc) of the prepared micelles in distilled water was determined by a fluorescence probe technique using pyrene. Indomethacin (IMC) as a model drug was incorporated into the micelles by dialysis and an oil/water emulsion method. Characteristics of PEO-PBLA micelles without and with the physically trapped IMC in the inner core of the micelles (IMC/PEO-PBLA) were studied by dynamic light scattering and gel permeation chromatography/HPLC as well as an in vitro release test of IMC from the micelles. For the PEO-PBLA block copolymers, N,N-dimethylacetamide (DMAc) was found to be the best of the solvents tested to form stable polymeric micelles with a narrow size distribution and avoid its aggregation, and the cmc of PEO-PBLA micelles thus prepared was determined to be ca. 18 mg/L in water. The diameters of PEO-PBLA micelles and IMC/PEO-PBLA micelles in number averaged scale were observed to be ca. 19 and 25-29 nm, respectively. The release study of IMC from IMC/PEO-PBLA micelles in various buffer solutions at the pH range from 1.2 to 7.4 at 37 degrees C revealed that the release rate of IMC from the micelles was increased by increasing the pH of the medium and indicated that the release rate of IMC from the micelles are controlled by the partition coefficient of IMC based on the pH of the medium and interaction between IMC and the hydrophobic portion of the micelles.

Chemistry, Pharmaceutical↗
PubMed2004

Variegated micelle surfaces: correlating the microstructure of mixed surfactant micelles with bulk solution properties.

Electron paramagnetic resonance, viscosity, and small-angle neutron scattering (SANS) measurements have been used to study the interaction of mixed anionic/nonionic surfactant micelles with the polyampholytic protein gelatin. Sodium dodecyl sulfate (SDS) and the nonionic surfactant dodecylmalono-bis-N-methylglucamide (C12BNMG) were chosen as "interacting" and "noninteracting" surfactants, respectively; SDS micelles bind strongly to gelatin but C12BNMG micelles do not. Further, the two surfactants interact synergistically in the absence of the gelatin. The effects of total surfactant concentration and surfactant mole fraction have been investigated. Previous work (Griffiths et al. Langmuir 2000, 16 (26), 9983-9990) has shown that above a critical solution mole fraction, mixed micelles bind to gelatin. This critical mole fraction corresponds to a micelle surface that has no displaceable water (Griffiths et al. J. Phys. Chem. B 2001, 105 (31), 7465). On binding of the mixed micelle, the bulk solution viscosity increases, with the viscosity-surfactant concentration behavior being strongly dependent on the solution surfactant mole fraction. The viscosity at a stoichiometry of approximately one micelle per gelatin molecule observed in SDS-rich mixtures scales with the surface area of the micelle occupied by the interacting surfactant, SDS. Below the critical solution mole fraction, there is no significant increase in viscosity with increasing surfactant concentration. Further, the SANS behavior of the gelatin/mixed surfactant systems below the critical micelle mole fraction can be described as a simple summation of those arising from the separate gelatin and binary mixed surfactant micelles. By contrast, for systems above the critical micelle mole fraction, the SANS data cannot be described by such a simple approach. No signature from any unperturbed gelatin could be detected in the gelatin/mixed surfactant system. The gelatin scattering is very similar in form to the surfactant scattering, confirming the widely accepted picture that the polymer "wraps" around the micelle surface. The gelatin scattering in the presence of deuterated surfactants is insensitive to the micelle composition provided the composition is above the critical value, suggesting that the viscosity enhancement observed arises from the number and strength of the micelle-polymer contact points rather than the gelatin conformation per se.

Journal Article↗
PubMed2001

Solute exchange between surfactant micelles by micelle fragmentation and fusion.

Stopped-flow time-scan experiments on both Triton X-100 (TX100) micelle and sodium dodecylsulfate (SDS) micelles, with the pyrene-containing triglyceride 1 as a probe, establish that there are two distinct solute exchange mechanisms with rates on the time scale of milliseconds to minutes. One process exhibits second order kinetics with a rate proportional to the concentration of empty micelles. For TX100 micelles, this process is rapid (k2 approximately 10(6) M(-1) s(-1) at 24.6 degrees C) and is characterized by an activation energy of 160 kJ mol(-1). From the fact that this rate is nearly independent of the structure of the probe we infer that the exchange involves micelle fusion to form a short-lived super-micelle, followed by fragmentation to form two normal (or 'proper') micelles. The rate of the first-order process decreases as the size of the probe increases (1-octylpyrene > 1-dodecylpyrene > 1). For SDS, both rates are very sensitive to the salt (NaCl) concentration. All indications point to this exchange process involving rate-limiting fragmentation of the micelle into two sub-micelles, these in turn grow back to normal micelles by addition of surfactant monomers or by collision with other sub-micelles. We explain the dependence of this rate on the nature of the probe by suggesting that only sub-micelles of a certain size are capable of carrying the probe with them as they separate from the original micelle.

Journal Article↗
PubMedDate not supplied

Polyion complex micelles of pDNA with acetal-poly(ethylene glycol)-poly(2-(dimethylamino)ethyl methacrylate) block copolymer as the gene carrier system: physicochemical properties of micelles relevant to gene transfection efficacy.

An acetal-poly(ethylene glycol)-poly(2-(dimethylamino)ethyl methacrylate) (acetal-PEG-PAMA) block copolymer spontaneously associated with plasmid DNA (pDNA) to form water-soluble complexes (polyion complex micelle: PIC micelle) in aqueous solution. Physicochemical characteristics and transfection efficiency of the PIC micelles thus prepared were studied here, focusing on the residual molar mixing ratio (N/P ratio) of AMA units in acetal-PEG-PAMA to the phosphate units in pDNA. With the N/P ratio increasing to unity, acetal-PEG-PAMA cooperatively formed complex micelles with pDNA through electrostatic interaction, allowing pDNA to condense effectively. Dynamic light scattering measurements revealed that the PIC micelle at N/P > or = 3 had a constant size of approximately 90-100 nm. Eventually, acetal-PEG-PAMA/pDNA micelles underwent no precipitation even after long-term storage for more than 1 month at all N/P ratios. The PIC micelles were stable even in the presence of excess polyanions, poly(vinyl sulfate), in contrast to polyplexes based on the PAMA homopolymer, yet this stabilization effect was highly dependent on the N/P ratio to reach a plateau at N/P = 3-4. This character may be attributed to the increased hydrophobicity in the vicinity of the complexed pDNA. Furthermore, the pDNA in the micelle was adequately protected from DNase I attack. The transfection ability of the PIC micelles toward 293 cells was remarkably enhanced with an increasing N/P ratio as high as 25. The zeta-potential of the micelles with a high N/P ratio was an appreciably large positive value, suggesting a noncooperative micelle formation. This deviated micellar composition with an excess cationic nature as well as the presence of free acetal-PEG-PAMA may play a substantial role in the enhanced transfection efficiency of the PIC micelle system in the high N/P ratio (approximately 25) region.

Cations↗
PubMed2005

Polymeric micelles for delivery of poorly soluble drugs: preparation and anticancer activity in vitro of paclitaxel incorporated into mixed micelles based on poly(ethylene glycol)-lipid conjugate and positively charged lipids.

Paclitaxel-loaded mixed polymeric micelles consisting of poly(ethylene glycol)-distearoyl phosphoethanolamine conjugates (PEG-PE), solid triglycerides (ST), and cationic Lipofectin lipids (LL) have been prepared. Micelles with the optimized composition (PEG-PE/ST/LL/paclitaxel = 12/12/2/1 by weight) had an average micelle size of about 100 nm, and zeta-potential of about -6 mV. Micelles were stable and did not release paclitaxel when stored at 4 degree C in the darkness (just 2.9% of paclitaxel have been lost after 4 months with the particle size remaining unchanged). The release of paclitaxel from such micelles at room temperature was also insignificant. However, at 37 degree C, approx. 16% of paclitaxel was released from PEG-PE/ST/LL/paclitaxel micelles in 72 h, probably, because of phase transition in the ST-containing micelle core. In vitro anticancer effects of PEG-PE/ST/LL/paclitaxel and control micelles were evaluated using human mammary adenocarcinoma (BT-20) and human ovarian carcinoma (A2780) cell lines. Paclitaxel in PEG-PE/ST/LL micelles demonstrated the maximum anti-cancer activity. Cellular uptake of fluorescently-labeled paclitaxel-containing micelles by BT-20 cells was investigated using a fluorescence microscopy. It seems that PEG-PE/ST/LL micelles, unlike micelles without the LL component, could escape from endosomes and enter the cytoplasm of BT-20 cancer cells thus increasing the anticancer efficiency of the micellar paclitaxel.

Antineoplastic Agents↗
PubMed1981

Location and orientation relative to the micelle surface for glucagon in mixed micelles with dodecylphosphocholine: EPR and NMR studies.

The spin labels, 5-doxylstearate, 12-doxylstearate, 16-doxylstearate and 1-oxyl-2,2,6,6-tetramethyl-4-dodecylphosphopiperidine, have been incorporated into dodecylphosphocholine micelles and mixed dodecylphosphocholine glucagon micelles. The EPR spectral parameters for the different spin labels and the 1H- and 13C-NMR relaxation rates for nuclei of the detergent molecules indicated that inclusion of up to one spin label molecule per micelle had little influence on the spatial organization of the micelles. Furthermore, the location and environment of the spin labels in the dodecylphosphocholine micelles were not noticeably affected by the addition of glucagon and the 1H-NMR spectra observed for glucagon in mixed spin label/deuterated dodecylphosphocholine/glucagon micelles showed that the different spin labels had essentially no effect on the conformation of glucagon. Approximate spatial locations within the micelle for the nitroxide moieties of the different spin labels were determined from the NMR relaxation rates observed for different nuclei of dodecylphosphocholine. On this basis, the line broadening of individually assigned glucagon 1H-NMR lines by the different spin labels was used to determine the approximate orientation of the polypeptide chain with respect to the micelle surface. Overall, the data indicate that the glucagon backbone runs roughly parallel to the micelle surface, with the depth of immersion adjusted so that polar and apolar side chains can be oriented towards the surface or interior of the micelle, respectively.

Choline↗
PubMed2006

Ultrafast photoinduced deligation and ligation dynamics: DCM in micelle and micelle-enzyme complex.

We report studies on diffusion controlled deligation and ligation dynamics of a probe ligand 4-(dicyanomethylene)-2-methyl-6-(p-dimethylamino-styryl) 4H-pyran (DCM) with cationic cetyltrimethylammonium bromide (CTAB) micelles. In order to investigate the effect of spatial heterogeneity on the dynamics we study the DCM labeled micelle upon complexation with an enzyme alpha-chymotrypsin (CHT). The variation of fluorescence line-width (Gamma(t)) of DCM in the complex and also in the micelle indicates the diffusion dynamics of DCM through various environments of different polarities. The temporal behavior of Gamma(t) reveals that at 50 mM CTAB concentration the excited DCM traverses 6.5 Angstrom distance from the surface of a host micelle (deligation) before entering to a stern layer of another adjacent micelle (ligation). From neutron scattering experiment the distance 6.5 Angstrom is found to be the thickness of a stern layer of CTAB micelle. No indication of ligation has been found at 2 mM CTAB concentration as the intermicellar distance is estimated to be very large (416 Angstrom) compared to the previous case. The dynamical behavior of Gamma(t) is also indicative of significantly slower diffusion of the ligand molecules (DCM) at the surface of the micelle in presence and absence of the enzyme compared to that in the bulk buffer. We have also studied the dynamics of solvation and local geometrical restriction on the probe DCM at the micellar surface with and without CHT. With picosecond time resolution, we found time constants of the solvation relaxation processes of the DCM labeled enzyme-micelle complex to be 230 ps (45%) and 870 ps (55%), which were comparable to those of the micelle without the enzyme. The time dependent anisotropy revealing local orientational motions of the probe in the complex was also found to be similar to that of DCM at the micellar surface in absence of CHT. These studies attempt to link the dynamical features for insight into the ligand mediated intercellular communication and the biological function of the enzyme alpha-chymotrypsin upon complexation with the CTAB micelle.

Anisotropy↗
PubMed1987

Physico-chemical studies of micelle formation on sepia cartilage collagen solutions in acetate buffer and its interaction with ionic and nonionic micelles. Hydrodynamic and thermodynamic studies.

Sepia cartilage collagen (pepsin-extracted) in acetate buffer (pH = 2.98) forms micelles at a particular concentration below which they do not normally form. The critical micelle concentration (cmc) of the collagen was determined in buffer as well as in SDS, cetyltrimethylammonium bromide (CTAB) and Tween-80 micellar environments at different temperatures. Mutual interaction of collagen micelles with the ionic and nonionic micelles through the formation of the mixed micelle concept has also been found. The cmc of collagen decreased in the presence of SDS and Tween-80 micelles whereas it increased in the presence of CTAB micelles. This clearly suggests that the micelle formation of collagen is facilitated by the presence of SDS and Tween-80 and hindered by CTAB micelles. The various thermodynamic parameters were estimated from viscosity measurements and the transfer of collagen into the micelles of various surfactants and the reverse phenomenon was analyzed. This analysis has also been modelled conceptually as a different phase and the results have supported the above phenomenon. Our thermodynamic results are also able to predict the exact denaturation temperature as well as the structural order of water in the collagen in various environments. The hydrated volumes, Vh, of collagen in the above environments and intrinsic viscosity were also calculated. The low intrinsic viscosity, [eta], of collagen in an SDS environment compared to buffer and other surfactant environments suggested more workable systems in cosmetic and dermatological skin care preparations. The one and two-hydrogen-bonded models of this collagen in various environments have been analyzed. The calculated thermodynamic parameters varied with the concentration of collagen. The change of thermodynamic parameters from coil-coil to random-coil conformation upon denaturation of collagen were calculated from the amount of proline and hydroxyproline residues and compared with viscometric results. Thermodynamic results suggest that the stability of the collagen in the additive environments is in the following order: SDS greater than Tween-80 greater than buffer greater than CTAB.

Acetates↗
PubMed1995

Localization of dipyridamole molecules in ionic micelles: effect of micelle and drug charges.

The localization of the coronary vasodilator dipyridamole (DIP) in cationic cetyltrimethylammonium chloride (CTAC), anionic sodium dodecylsulfate (SDS) and zwitterionic N-hexadecyl-N,N-dimethyl-3-ammonio-1-propanesulfonate and lysophosphatidylcholine (HPS and LPC) micelles was investigated using fluorescence quenching by quenchers with known localization in the micelle (TEMPO and 5-doxyl and 12-doxyl stearic acids). The use of fluorescence quenching jointly with fluorescence and 1H-NMR spectral measurements shows that DIP molecules in both protonated and nonprotonated forms are localized in micelles near the region which separates their polar and nonpolar parts, the polarizable heteroaromatic cycle of DIP being close to the polar part and the nonpolar substituents penetrating the hydrophobic interior of the micelle. The electrostatic interaction between the protonated DIP molecules and micelle charges either moves DIP into the micelle interior (for cationic and zwitterionic micelles) or draws it closer to the micelle surface (for anionic ones). Our results could be relevant to the mechanism of DIP action since many data indicate the interaction of the drug with cell membranes. The ability of DIP to localize near the membrane surface with the substituents immersed into a hydrophobic moiety could be essential for the drug interaction with P-glycoprotein, which is responsible for mediation of the effects of several antitumour drugs.

Dipyridamole↗
PubMed2003

Micelle formation of sodium chenodeoxycholate and solubilization into the micelles: comparison with other unconjugated bile salts.

Micellization of sodium chenodeoxycholate (NaCDC) was studied for the critical micelle concentration (CMC), the micelle aggregation number, and the degree of counterion binding to micelle at 288.2, 298.2, 308.2, and 318.2 K. They were compared with those of three other unconjugated bile salts; sodium cholate (NaC), sodium deoxycholate (NaDC), and sodium ursodeoxycholate (NaUDC). The I(1)/I(3) ratio of pyrene fluorescence and the solubility dependence of solution pH were employed to determine the CMC values. As the results, a certain concentration range for the CMC and a stepwise molecular aggregation for micellization were found reasonable. Using a stepwise association model of the bile salt anions, the mean aggregation number (n) of NaCDC micelles was found to increase with the total anion concentration, while the n values decreased with increasing temperature; 9.1, 8.1, 7.4, and 6.3 at 288.2, 298.2, 308.2, and 318.2 K, respectively, at 50 mmol dm(-3). The results from four unconjugated bile salts indicate that the number, location, and orientation of hydroxyl groups in the steroid nucleus are quite important for growth of the micelles. Activity of the counterion (Na(+)) was determined by a sodium ion selective electrode in order to confirm the low counterion binding to micelles. The solubilized amount of cholesterol into the aqueous bile salt solutions increased in the order of NaUDC<NaC<NaCDC<NaDC. The first stepwise association or solubilization constants (K(1)) between a cholesterol monomer and a vacant micelle were evaluated at different bile salt concentrations. The constants were also determined for polycyclic aromatic compounds (benzene, naphthalene, anthracene, and pyrene). The corresponding DeltaG(0) value was most negative for cholesterol among the solubilizates studied, which indicated that cholesterol was thermodynamically stabilized most by solubilization into the bile salt micelles.

Bile Acids and Salts↗
PubMed2001

Separation and selectivity of benzophenones in micellar electrokinetic chromatography using sodium dodecyl sulfate micelles or sodium cholate modified mixed micelles.

The separation and selectivity of nine benzophenones in micellar electrokinetic chromatography (MEKC) using sodium dodecyl sulfate (SDS) micelles or sodium cholate (SC) modified mixed micelles were investigated in the pH range 6.5-8.0. The results indicate that the combined effects of buffer pH and SC concentration can greatly affect the separation and selectivity of benzophenones, particularly for benzophenones possessing a hydroxyl substituent at the 4-position of the aromatic ring with respect to the carbonyl moiety when using SDS-SC mixed micelles. Better separability can be obtained with SDS-SC mixed micelles than with SDS micelles. Complete separation of nine benzophenones in MEKC can be achieved with an appropriate choice of buffer pH and the concentration of SDS micelles or SC modified mixed micelles. The dependence of the migration order of those benzophenones based on their structures and solute-micelle interactions is discussed.

Benzophenones↗
PubMed2003

Polyion complex micelles from plasmid DNA and poly(ethylene glycol)-poly(L-lysine) block copolymer as serum-tolerable polyplex system: physicochemical properties of micelles relevant to gene transfection efficiency.

Polyion complex (PIC) micelles composed of the poly(ethylene glycol)-poly(L-lysine) (PEG-PLL) block copolymer and plasmid DNA (pDNA) were investigated in this study from a physicochemical viewpoint to get insight into the structural feature of the PIC micellar vector system to show practical gene transfection efficacy particularly under serum-containing medium. The residual ratio (r) of the lysine units in PEG-PLL to the phosphate units of pDNA in the system significantly affects the size of the PIC micelles evaluated from dynamic light scattering, being decreased from approximately 120 to 80 nm with an increase in the r value for the region with r > or = 1.0. The zeta potential of the complexes slightly increased with r in the same region, yet maintained a very small absolute value and leveled off to a few mV at r approximately 2.0. These results suggest that the micelles are most likely to take the core-shell structure with dense PEG palisades surrounding the PIC core to compartmentalize the condensed pDNA. Furthermore, an increasing r value in the region of r > or = 1 induces a rearrangement of the stoichiometric complex formed at r=1.0 to the non-stoichiometric complex composed of the excess block copolymer. The association number of pDNA and the block copolymer in the micelle was estimated from the apparent micellar molecular weight determined by static light scattering measurements, indicating that a single pDNA molecule was incorporated in each of the micelles prepared from the PEG (Mw=12,000 g/mol)-PLL (polymerization degree of PLL segment: 48) (12-48) block copolymer at r=2.0. These 12-48/pDNA micelles showed a gene expression comparable to the lipofection toward cultured 293 cells, though 100 microM chloroquine was required in the transfection medium. Notably, even in the presence of serum, the PIC micelles achieved appreciable cellular association to attain a high gene expression, which is in sharp contrast with the drastic decrease in the gene expression for lipoplex system in the presence of serum. A virus-comparable size (approximately 100 nm) with a serum-tolerable property of the PIC micelles indeed suggests their promising feasibility as non-viral gene-vector systems used for clinical gene therapy.

Biocompatible Materials↗
PubMed2006

Block copolymer micelles as delivery vehicles of hydrophobic drugs: micelle-cell interactions.

One-third of drugs in development are water insoluble and one-half fail in trials because of poor pharmacokinetics. Block copolymer micelles are nanosized particles that can solubilize hydrophobic drugs and alter their kinetics in vitro and in vivo. However, block copolymer micelles are not solely passive drug containers that simply solubilize hydrophobic drugs; cells internalize micelles. To facilitate the development of advanced, controlled, micellar drug delivery vehicles, we have to understand the fate of micelles and micelle-incorporated drugs in cells and in vivo. With micelle-based drug formulations recently reaching clinical trials, the impetus for answers is ever so strong and detailed studies of interactions of micelles and cells are starting to emerge. Most notably, the question arises: Is the internalization of block copolymer micelles carrying small molecular weight drugs an undesired side effect or a useful means of improving the effectiveness of the incorporated drugs?

Drug Delivery Systems↗
PubMed1990

Rapid (1 hour) high performance gel filtration chromatography resolves coexisting simple micelles, mixed micelles, and vesicles in bile.

We describe the use and validation of Superose 6, a high performance gel filtration medium for rapid, high resolution separation and sizing of coexisting simple micelles, mixed micelles, and vesicles in bile. We fractionated model biles (1.7-4.2 g/dl total lipid concentration, 0.15 M NaCl) composed of lecithin (L), cholesterol (Ch), and the common bile salt taurocholate (TC) using Superose 6 gel filtration columns (1.0 cm diameter, 30 cm length, 0.5 ml model bile application, 1.0 ml fractions) pre-equilibrated and eluted with 2.5-10.0 mM TC. Lipid particle sizes were determined by quasielastic light scattering and lipid compositions by conventional analyses. In the absence of L and Ch, pure TC "biles" (32.2 mM), when eluted in the presence of 7.5 mM TC, yielded a single peak of particles (mean hydrodynamic radii, Rh values of 11-15 A), consistent with simple TC micelles. Model biles containing L and TC ([L] = 13.8 mM, [TC] = 32.2 mM) were fractionated with baseline resolution into TC-L mixed micelles, (Rh values of 30-40 A) and simple TC micelles. In agreement with the ternary TC-L-H2O phase diagram (Mazer, N. A., et al. 1980. Biochemistry. 19: 601-615), the proportions of simple and mixed micelles were inversely related to L concentrations ([L] = 0-32.2 mM) and correlated positively with eluant TC concentration. Superose 6 gel fractionation of model biles "super-saturated" with Ch (TC:L:Ch molar ratio 27:63:10, total lipid concentration 3 g/dl) yielded high resolution separation of vesicles (Rh value of 320 A) from mixed micelles of TC-L-Ch (Rh values of 40-50 A) and simple TC micelles (Rh values of 11-15 A). At an eluant TC concentration of 7.5 mM, Ch-rich vesicles (Ch/L molar ratio = 1.6) separated that contained 40% of total Ch, 9% of total L, and no TC, accurately reflecting predictions of the quaternary L-Ch-TC-H2O metastable phase diagram (Mazer, N. A., and M. C. Carey. 1983 Biochemistry. 22: 426-442). This suggested that a 7.5 mM TC concentration approximated the intermicellar concentration under the experimental conditions. We also fractionated an identical model bile using conventional Sephacryl S-300, a medium generally used to study model and native biles. Compared with Superose 6, the Sephacryl S-300 column of equivalent size yielded particle separations with lower resolution and speed (30 h v l h).(ABSTRACT TRUNCATED AT 400 WORDS)

Bile↗
PubMed1997

The interaction of quinone and detergent with reaction centers of purple bacteria. I. Slow quinone exchange between reaction center micelles and pure detergent micelles.

The kinetics of light-induced electron transfer in reaction centers (RCs) from the purple photosynthetic bacterium Rhodobacter sphaeroides were studied in the presence of the detergent lauryldimethylamine-N-oxide (LDAO). After the light-induced electron transfer from the primary donor (P) to the acceptor quinone complex, the dark re-reduction of P+ reflects recombination from the reduced acceptor quinones, QA- or QB-. The secondary quinone, QB, which is loosely bound to the RC, determines the rate of this process. Electron transfer to QB slows down the return of the electron to P+, giving rise to a slow phase of the recovery kinetics with time tau P approximately 1 s, whereas charge recombination in RCs lacking QB generates a fast phase with time tau AP approximately 0.1 s. The amount of quinone bound to RC micelles can be reduced by increasing the detergent concentration. The characteristic time of the slow component of P+ dark relaxation, observed at low quinone content per RC micelle (at high detergent concentration), is about 1.2-1.5 s, in sharp contrast to expectations from previous models, according to which the time of the slow component should approach the time of the fast component (about 0.1 s) when the quinone concentration approaches zero. To account for this large discrepancy, a new quantitative approach has been developed to analyze the kinetics of electron transfer in isolated RCs with the following key features: 1) The exchange of quinone between different micelles (RC and detergent micelles) occurs more slowly than electron transfer from QB- to P+; 2) The exchange of quinone between the detergent "phase" and the QB binding site within the same RC micelle is much faster than electron transfer between QA- and P+; 3) The time of the slow component of P+ dark relaxation is determined by (n) > or = 1, the average number of quinones in RC micelles, calculated only for those RC micelles that have at least one quinone per RC (in excess of QA). An analytical function is derived that relates the time of the slow component of P+ relaxation, tau P, and the relative amplitude of the slow phase. This provides a useful means of determining the true equilibrium constant of electron transfer between QA and QB (LAB), and the association equilibrium constant of quinone binding at the QB site (KQ+). We found that LAB = 22 +/- 3 and KQ = 0.6 +/- 0.2 at pH 7.5. The analysis shows that saturation of the QB binding site in detergent-solubilized RCs is difficult to achieve with hydrophobic quinones. This has important implications for the interpretation of apparent dependencies of QB function on environmental parameters (e.g. pH) and on mutational alterations. The model accounts for the effects of detergent and quinone concentration on electron transfer in the acceptor quinone complex, and the conclusions are of general significance for the study of quinone-binding membrane proteins in detergent solutions.

Benzoquinones↗