Small Micelles Research Articles

Cell-Selective Pore Forming Antimicrobial Peptides of the Prodomain of Human Furin: A Conserved Aromatic/Cationic Sequence Mapping, Membrane Disruption, and Atomic-Resolution Structure and Dynamics.

Antimicrobial peptides are promising molecules in uprising consequences of drug-resistant bacteria. The prodomain of furin, a serine protease, expressed in all vertebrates including humans, is known to be important for physiological functions. Here, potent antimicrobial peptides were mapped by extensive analyses of overlapping peptide fragments of the prodomain of human furin. Two peptides, YR26 and YR23, were active against bacterial cells including MRSA-resistant Staphylococcus aureus and Staphylococcus epidermis 51625. Peptides were largely devoid of hemolytic and cytotoxic activity. Bacterial cell killing occurred as a result of the disruption of the permeability barrier of the lipopolysaccharide (LPS)-outer membrane and fragmentation of LPS into small micelles. Furthermore, antibacterial peptides specifically interacted with the negatively charged lipids causing membrane leakage and fusion. The YR26 peptide in sodium dodecyl sulfate micelles demonstrated a long-helix-turn-short-helix structure exhibiting restricted backbone motions. The cell-selective activity of the furin peptides and their unique mode of action on membranes have a significant potential for the development of therapeutics.

Self-Assembly and Chiral Recognition of Chiral Cationic Gemini Surfactants.

Chiral cationic gemini surfactants 1,4-bis(dodecyl- N, N-dimethylammonium bromide)-2,3-butanediol (12-4(OH)2-12) including racemate, mesomer, and two enantiomers were synthesized and their self-assembly in aqueous solution has been comparatively investigated by tensiometry, conductometry, 1H NMR, small-angle neutron scattering, cryogenic transmission electron microscopy, and cryogenic scanning electron microscopy. The chirality at spacer induces different self-assembly behaviors due to the hydrogen-bonding interaction between the hydroxyl groups at the chiral centers. The stereochemistry of the spacer has little effect on the release of the counterions from the surfactant headgroups and on the molecular packing at the air-water interface. The critical micelle concentration (CMC) decreases in the order of racemate > enantiomer > mesomer. Above the CMC, the aggregates of enantiomers transit from small spherical micelles to rodlike and wormlike micelles with increasing concentration, whereas the mesomer and racemate aggregates transform from spherical micelles to rodlike micelles and platelet-like aggregates. The differences may be because the mesomer and racemate molecules mainly form intermolecular hydrogen bonds between the -OH groups, but the enantiomer molecules dominantly form intramolecular hydrogen bonds. Furthermore, it was found that the chiral micelles formed by the enantiomers exhibit enantioselection ability for bilirubin (BR) enantiomers. The recognition capability can be adjusted by the micellar structure, i.e., the rodlike micelles are better than either small spherical micelles or wormlike micelles, which might possess different chiral cavities, controlling BR shape and location. These results demonstrate that the aggregates of chiral gemini surfactants can be used to mimic the chiral recognition in biological membrane.

UV-Responsive Behavior of Multistate and Multiscale Self-Assemblies Constructed by Gemini Surfactant 12-3-12·2Br- and trans- o-Methoxy-cinnamate.

Photoresponsive systems with adjustable self-assembly morphologies and tunable rheological properties have aroused widespread concern of researchers in recent years because of their prospect applications in controlled release, microfluidics, sensors, and so forth. In this paper, we combine a cationic Gemini surfactant 12-3-12·2Br- and trans-2-methoxy-cinnamate ( trans-OMCA) together to create a representative UV-responsive self-assembly system. The system displays abundant self-assembly behaviors, and the self-assemblies with different states and different scales including wormlike micelles, vesicles, and lyotropic liquid crystals (LCs) as well as an aqueous two-phase system (ATPS) are observed even at lower surfactant concentration. The UV-responsive behavior of the formed self-assemblies is investigated systematically. The results have shown that the photoisomerization of OMCA from trans form to cis form under UV light irradiation alters the hydrophobicity and steric hindrance effect of OMCA and thus affects the molecular packing at the micellar interface and further leads to the transformation of assembly morphologies. The long wormlike micelles can gradually transform into much shorter rodlike micelles under UV irradiation and companied by the decrease of solution viscosity by 2 orders of magnitude. In addition, the vesicles can evolve into multistate self-assembly structures including the ATPS, wormlike micelles, rod-like micelles, and small spherical micelles depending on the UV irradiation time. The ATPS and its adjacent anisotropic LC phase can respectively combine into a single phase and separate into ATPS under UV irradiation. The morphologies of assemblies in the 12-3-12·2Br-/ trans-OMCA mixed system can be tailored by adjusting the system composition and duration of UV light irradiation on purpose. The photoresponsive system with abundant self-assembly behaviors and tunable rheological properties has wide application prospect in numerous fields such as drug delivery, materials science, smart fluids, and so forth, and the macroscopic phase separation and combination provide novel strategies for effective separation and purification of certain substances.

DOTA Functionalized Cross-Linked Small-Molecule Micelles for Theranostics Combining Magnetic Resonance Imaging and Chemotherapy.

Herein, a new theranostic nanoplatform was built by introducing DOTA on the surface of the cross-linked small molecular micelles. This nanoplatform consisted of three parts: (1) Hydrophobic alkyl chain functioned with alkenes as cross-linkable part to ensure the robust stability in vivo; (2) Hydrophilic DOTA for not only gadolinium ions complexion as MR imaging contrast agents but also platinum ions complexion as drug carriers; (3) Cisplatin as antitumor drug and MR imaging amplifier simultaneously. The metal loading content of the resulting Pt/Gd@DOTA-CSMs was up to 12 and 14 wt % for Gd(III) and Pt(II), respectively. The longitudinal relaxation rate of Gd@DOTA-CSMs (8.46 mM-1 s-1) was 2.6 times than that of the clinical Gd-DTPA (3.23 mM-1 s-1). When cisplatin was involved, not only great antitumor efficiency was achieved, but higher longitudinal relaxation rate of Pt/Gd@DOTA-CSMs (11.17 mM-1 s-1) was carried out due to the extension of rotational correlation time. The experiments of Balb/c mice bearing 4T1 xenograft indicated that Pt/Gd@DOTA-CSMs had better antitumor activity, lower side effect than clinically used cisplatin, and greater MR imaging than Gd-DTPA. All the results proved that the nanoplatform of DOTA-CSMs held remarkable potential in the field of therapeutics.

Synergistic Interaction and Aggregation Behavior in a Mixture of a Tripolar Zwitterionic Surfactant and an Anionic Surfactant

AbstractThe aggregation behavior of a tripolar zwitterionic surfactant (C14C6Tri) with sodium dodecyl sulfate (SDS) in aqueous solution at various molar fractions was investigated using surface tension, turbidity, dynamic light scattering, ζ potential, and cryogenic transmission electron microscopy. The C14C6Tri carries 2 cationic ammonium headgroups and 1 anionic sulfonate headgroup, and the 2 ammonium headgroups are linked by a 6‐methylene chain while the sulfonate group is connected with one of the ammonium headgroups by a 3‐methylene chain. The surface activity parameters, the composition of mixed micelles, and the interaction parameter (β) were evaluated using an ideal mixing model and the regular solution model. The strong synergistic effect between C14C6Tri and SDS leads to a striking reduction in the critical micellar concentration and surface tension values. Both the interaction parameters at the air–water interface (βσ) and in the mixed micelles (β m) are large negative values. Moreover, the aggregate structures of the C14C6Tri/SDS mixture can be regulated by changing the molar fraction and the concentration. Upon increasing the molar fraction of SDS, the aggregate transitions take place from spherical micelles to vesicles, rod‐like micelles, and spherical micelles at a total surfactant concentration of 2.00 mM, while only small spherical micelles exist as the total surfactant concentration increases to 20.00 mM. The large headgroup, multi‐binding sites and variable conformation of C14C6Tri are responsible for the abundant aggregation behaviors.

Geometrical and Structural Dynamics of Imatinib within Biorelevant Colloids.

Solubilization of lipophilic drugs is essential for efficient uptake. We detail the solubilization of imatinib in simulated gastrointestinal fluids containing taurocholate (TC) and lecithin (L) and reflecting fasted versus fed states using NMR spectroscopy, X-ray diffractometry, transmission electron microscopy, and dynamic light scattering analysis. Imatinib concentration impacted colloidal geometries and molecular dynamics in a fasted state. At drug substance concentrations up to 250 μM, imatinib was mainly engulfed within the core of >110 nm in diameter vesicles. At higher drug concentrations, the colloids collapsed to <40 nm, and imatinib migrated into the shell of the micelles, mainly being associated with the lipophilic face of TC but not with L. Simulating the fed state resulted in the formation of small micelles independent of the drug concentration. Furthermore, a hydrogel was formed, effectively keeping the drug substance in an amorphous state even when stressed by drying. In conclusion, this study detailed the fascinating dynamics of colloidal structures and molecular assembly as a function of imatinib concentration in biorelevant conditions. This approach may provide a blueprint for the rational development of future pharmaceutical formulations, taking the molecular interactions with bile salts/phospholipids into account.

Self-Healing and Multistimuli-Responsive Hydrogels Formed via a Cooperation Strategy and Their Application in Detecting Biogenic Amines.

We reported here a new platform of supramolecular hydrogels cross-linked by the cooperation of metal-ligand coordination and hydrophobic interaction. A salicylaldehyde benzoyl hydrazone-terminal poly(ethylene glycol) (2SBH-PEG) was synthesized and formed small micelles in an aqueous environment. Addition of Ni2+ connected the low-molecular-weight 2SBH-PEG into a metallopolymer via metal-ligand coordination and led to micelle aggregation, resulting in gelation due to the enhancement of hydrophobic interaction. The forming hydrogel, Ni-PEGel, exhibited rapid self-healing ability and reversible pH-responsive property. Because of the containing metal coordination bond, it was also sensitive to the strong competing ligands, such as ethylenediaminetetraacetic acid (EDTA)and pyridine. In addition, Ni-PEGel showed colorimetric changes when exposed to biogenic amine (BA) vapor. The color development of Ni-PEGel toward BAs makes it a good candidate in monitoring food spoilage.

A comparison of the self-assembly behaviour of sodium N-lauroyl sarcosinate and sodium N-lauroyl glycinate surfactants in aqueous and aqueo-organic media

Self-assembly of surfactants is influenced by various intermolecular interactions and molecular structure, which dictate packing of molecules in the aggregate and its microstructure. Hydrogen-bonding between amide groups plays a key role in the self-assembly process of N-acyl amino acid surfactants (NAAS). The self-assembly properties of two NAAS, sodium N-lauroyl sarcosinate (SLS) and sodium N-lauroyl glycinate (SLG) that differ only in the head-group structure were compared in aqueous and aqueo-organic media by using a number of methods, including surface tension fluorescence, dynamic light scattering, calorimetry, and microscopy. It was observed that aggregate formation is more favoured in SLG. Studies revealed that while SLS formed small spherical micelles, SLG produced unilamellar vesicles in pH 7 buffer above critical micelle concentration at 25 °C. The stability of SLG vesicles with respect to pH and temperature was also investigated. Furthermore, both SLG and SLS were found to gelify aquo-organic mixtures of varying composition upon heat-cool treatment. Their gelation behaviour was compared by measuring minimum gelation concentration, molecular packing, and morphology and mechanical stability of the thermoreversible gels. The difference in self-assembly behaviour in water as well as in aqueo-organic mixtures was attributed to the steric repulsion and hydrogen-bonding interaction at the head-group of the molecules.

1-Butanol as a Solvent for Efficient Extraction of Polar Compounds from Aqueous Medium: Theoretical and Practical Aspects.

The extraction of polar molecules from aqueous solution is a challenging task in organic synthesis. 1-Butanol has been used sporadically as an eluent for polar molecules, but it is unclear which molecular features drive its efficiency. Here, we employ free energy simulations to study the partitioning of 15 solutes between water and 1-butanol. The simulations demonstrate that the high affinity of polar molecules to the wet 1-butanol phase is associated with its nanostructure. Small inverse micelles of water are able to accommodate polar solutes and locally mimic an aqueous environment. We verify the simulations based on partition coefficients between water and 1-octanol, and include a blind prediction of the water/1-butanol partition coefficient of cyclohexane-1,2-diol. The calculations are in excellent agreement with experiment, reaching root-mean-square deviations below 0.7 kcal/mol. Actual extractions of cyclohexane-1,2-diol from buffer solutions that mimic cell lysates and suspensions in biocatalytic reactions further exemplify our findings. The yields highlight that extractions with 1-butanol can be significantly more efficient than the conventional protocol based on ethyl acetate.

A theoretical investigation of the influence of the second critical micelle concentration on the solubilization capacity of surfactant micelles

The solubilization of hydrophobic components by surfactants that form microemulsion droplets has been investigated from a theoretical point of view. By means of combining thermodynamics of self-assembly to form small systems with bending elasticity theory, we have been able to demonstrate a strong correlation between the second critical micelle concentration (CMC2) of surfactant micelles and their solubilization capacity (σ). The correlation may be rationalized as a consequence of all three bending elasticity constants spontaneous curvature (H0), bending rigidity (kc) and saddle-splay constant (k¯c) showing similar trends with respect to the two quantities, i.e. σ increases and CMC2 decreases with decreasing values of kcH0 and increasing values of kc and k¯c, respectively. As a result, we demonstrate that the solubilization capacity is predicted to always be higher for a gemini surfactant with CMC2 = 11 mM as compared with a gemini surfactant with CMC2 = 18 mM. The predicted correlation between solubilization capacity and CMC2 agrees with experimental observations showing that surfactants forming larger micelles in general have better solubilization capacity than surfactants forming smaller micelles. The theory also demonstrates, in agreement with experiments, that σ is raised in the entire range of surfactant concentrations, below as well as above CMC2, regardless of micelle size. Consequently, our theory predicts that small micelles formed below CMC2 increase in size, whereas large rodlike or wormlike micelles formed above CMC2 decrease in size, as a hydrophobic solubilizate is added to a micellar solution.

Effective treatment of the primary tumor and lymph node metastasis by polymeric micelles with variable particle sizes

Nanoparticles (NPs) offer new solutions for the diagnosis and treatment of tumors. However, the anti-tumor effect has not been greatly improved. Tumors are easily spread through the lymphatic system while the traditional NPs (~100 nm) can hardly reach lymph nodes for the treatment of metastasis. In addition, the NPs with fixed particle size cannot achieve efficient “penetration” and long-term “retention” simultaneously. Herein, we established “transformable” micelles modified with azide/alkyne groups for click chemical reaction. Not surprisingly, the small micelles (~25 nm) could effectively target lymph nodes, limiting the growth of the metastases associated with their size-regulated abilities to extravasate from the vasculature. Tumor lymph node metastasis dropped by 66.7%. After reaching primary tumors, cycloaddition reaction occurred between groups on micelles, resulting in the formation of aggregates. The strategy resulted in improved retention of the micelles in 4 T1 cells both in vitro and in vivo owing to the decreasing of nanoparticle exocytosis and minimizing the backflow to the bloodstream. Enhanced cytotoxicity on 4 T1 cells and improved antitumor efficacy were also observed. S-PTX (+) exhibited 76.23% tumor suppression, and tumor mass at the end of the treatment also showed the best tumor inhibitory effect. In conclusion, this drug delivery system provides a strategy for effective treatment of the primary tumor and lymphatic metastasis.

Chain terminal group leads to distinct thermoresponsive behaviors of linear PNIPAM and polymer analogs

Poly(alkylacrylamides), most notably poly(N-isopropylacrylamide) (PNIPAM), are widely studied thermoresponsive polymers. Linear PNIPAM, poly(N-n-propylacrylamide) (PNnPAM) and poly(N-cyclopropylacrylamide) (PNCPAM) were synthesized via RAFT polymerization to obtain polymers with low dispersity and varying terminal groups. The polymers were studied with a combination of small-angle neutron scattering (SANS), turbidimetry measurements, and dissipative particle dynamics (DPD) simulations to determine the influence of terminal group and monomer structure on assembly and thermoresponsive behavior in solution. Large scale, fractal assemblies (larger than 1 μm) are observed below the critical temperature for polymers terminated with short hydrophobic groups, but for long hydrophobic terminal groups, polymers formed small micelles (ca. 15 nm). The two cases give rise to two distinct thermoresponsive behaviors: the fractal assemblies display the traditional coil-to-globule behavior, whereas the corona of the micelles collapsed well below the critical temperature due to n-clustering, while the micelles remained in solution. The results indicate that, despite making up only a small fraction of the polymer, the terminal groups play a large role in both the conformation and assembly of PNIPAM and its analogs below the critical temperature, and hints at the possibility of new design strategies for thermoresponsive materials.

Persistent optical hole-burning spectroscopy of nano-confined dye molecules in liquid at room temperature: Spectral narrowing due to a glassy state and extraordinary relaxation in a nano-cage.

Persistent optical hole-burning spectroscopy has been conducted for a dye molecule within a very small (∼1 nm) reverse micelle at room temperature. The spectra show a spectral narrowing due to site-selective excitation. This definitely demonstrates that the surroundings of the dye molecule are in a glassy state regardless of a solution at room temperature. On the other hand, the hole-burning spectra exhibit large shifts from excitation frequencies, and their positions are almost independent of excitation frequencies. The hole-burning spectra have been theoretically calculated by taking account of a vibronic absorption band of the dye molecule under the assumption that the surroundings of the dye molecule are in a glassy state. The calculated results agree with the experimental ones that were obtained for the dye molecule in a polymer glass for comparison, where it has been found that the ratio of hole-burning efficiencies of vibronic- to electronic-band excitations is quite high. On the other hand, the theoretical results do not explain the large spectral shift from the excitation frequency and small spectral narrowing observed in the hole-burning spectra measured for the dye-containing reverse micelle. It is thought that the spectral shift and broadening occur within the measurement time owing to the relaxation process of the surroundings that are hot with the thermal energy deposited by the dye molecule optically excited. Furthermore, the relaxation should be temporary because the cooling of the inside of the reverse micelle takes place with the dissipation of the excess thermal energy to the outer oil solvent, and so the surroundings of the dye molecule return to the glassy state and do not attain the thermal equilibrium. These results suggest that a very small reverse micelle provides a unique reaction field in which the diffusional motion can be controlled by light in a glassy state.

Polyelectrolyte micelles in salt‐free solutions: Micelle size and electrostatic potential

ABSTRACTThe structural and electrical characteristics of polyelectrolyte micelles formed by diblock copolymers with one charged block and one solvophobic block are studied by the means of molecular dynamics simulations using the Primitive model at different Bjerrum lengths. The properties of interest are the mean aggregation number, the shape, the electrical potential as a function of the distance of the micelle's center of mass and the zeta potential. We found that for partially charged short A blocks the micelles’ mass distribution function is at least bimodal, indicating the coexistence of small and large micelles in agreement with theoretical and experimental findings. The zeta potential is not a monotonic function of the length of the charged block. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2018, 56, 924–934

Phase behaviour, micellar structure and linear rheology of tetrablock copolymer Tetronic 908

Tetronics are X-shaped block-copolymers of polyethylene oxide and polypropylene oxide, which self-assemble into micelles and can undergo a sol-gel transition; these transitions are dependent on temperature, concentration but also pH, due to the central diamine group of the tetrablock. We report the nanoscale morphologies underlying these different phases and the rheology of the systems for a very large, highly hydrophilic block copolymer, Tetronic 908, through the combined use of oscillatory rheology, steadyblock-state and time-resolved fluorescence, small-angle neutron scattering (SANS), dynamic light scattering (DLS) and Fourier transform infrared attenuated total reflectance (FTIR-ATR). At low concentrations, SANS reveal core-shell micelles of ca. 10 nm radius, presenting a dehydrated core and a highly hydrated shell, with relatively small aggregation numbers (Nagg ≈ 13). The micelles are notably affected by the pH, due to the protonation of the central amine spacer at low pH (pH ≈ 2), which shifts micellization to higher temperature, with smaller micelles than at natural pH. In the intermediate concentration regime (10–15%), micelles become smaller (Nagg ≈ 5), and present a higher hydration of the core. In the high concentration regime, Tetronic 908 undergoes a sol-gel transition above a threshold temperature, which is fully inhibited at acidic pH. SANS data from the gel phase reveal a BCC order of tightly packed spheres. Temperature sweeps in oscillatory rheology show a shift of the onset of gelation towards lower temperatures as concentration increases, an increase in the elastic modulus G′ and an expansion of gel region over a larger range of temperatures. SANS and rheology reveal that at pH below the natural pH (ca. 8), gelation is shifted to higher temperatures, but the morphology of the gels is similar, while under highly acidic conditions the gelation is fully suppresed.

Solubilization ability of N,N-dimethyl-N-alkyladamantylammonium bromide

Adamantane is difficult to dissolve in water owing to its bulky steric hydrocarbon structure. We designed a novel amphiphilic molecule by introducing an alkyl chain and a cation group into an adamantyl group. N,N-dimethyl-N-alkyladamantylammonium bromide (CnAdAB; n is the alkyl chain length, where n=10, 12, and 14) dissolves easily in water by forming micelles above the critical micelle concentration. Aggregates of this surfactant series form small nonspherical micelles several nanometers in size with relative small aggregation number; 53 (n=10), 59 (n=12), and 63 (n=14) at the typical concentration. Small-angle X-ray scattering measurement showed that the micellar structure of C12AdAB was changed slightly by solubilization of naphthalene and stearic acid. Moreover, the solubilization ability of the aggregates was studied using naphthalene and long-alkyl-chain fatty acids (myristic, palmitic, and stearic acids). The same solubilization experiments were performed using typical cationic surfactants (dodecyltrimethylammonium bromide and a gemini surfactant) for comparison. The molar solubilization ratios indicate that the CnAdAB series can solubilize the aromatic compound naphthalene as well as the other surfactants, whereas they can barely solubilize the long-alkyl-chain fatty acids. The solubilization stability can be analyzed by estimating the Gibbs free energy change (ΔG0) for the transfer of solubilizate molecules to the aggregate phase. The gemini surfactant system showed the largest negative value of ΔG0 for both naphthalene and the fatty acids. On the other hand, solubilization of fatty acids into CnAdAB micelles was not advantageous energetically. These results indicate that the solubilization ability of CnAdAB surfactants is not generally suitable for solubilization of long-alkyl-chain fatty acids owing to the smallness of the micelles.

Effect of the morphology of adsorbed oleate on the wettability of a collophane surface

The adsorption of surfactants on a solid surface could alter its wettability, which offers a wide range of relevant applications such as mineral flotation, hydrophobic material preparation and nanomaterial dispersion. The morphology of adsorbed oleate on a collophane surface was visualized using the peakforce tapping mode of atomic force microscopy (AFM), and its effect on the wettability of collophane was analysed by contact angle measurements, adsorption measurements and molecular dynamics (MD) simulations. The AFM images demonstrated that the adsorbed structure varied with different oleate concentrations. First, the small cylindrical micelles with concomitant monolayer and bilayer structures were observed above the hemimicelle concentration (hmc) of 1 × 10−5 mol/L, which enhanced the hydrophobicity of the collophane surface, and the collophane surface was not completely covered with the oleate monolayer due to surface heterogeneity. Then, large cylindrical micelles with a major bilayer were formed as the critical micelle concentration (cmc) of 1 × 10−3 mol/L was approached, which decreased its hydrophobicity, and finally the formation of large cylindrical micelles with multilayer at the cmc caused the hydrophilicity of the collophane surface. Therefore, there was a suitable equilibrium concentration between the hmc and cmc for oleate as a collector during mineral flotation, and oleate could also be used as a dispersant for colloidal stability when its equilibrium concentration reached the cmc. The effect of the adsorbed structure on the wettability of collophane was also confirmed by MD simulations. This study provides a good understanding of the surface modification of particles by surfactants for flotation and dispersion applications.

Solution Self-Assemblies of Sequence-Defined Ionic Peptoid Block Copolymers.

A series of amphiphilic ionic peptoid block copolymers where the total number (1 or 3) and position of ionic monomers along the polymer chain are precisely controlled have been synthesized by the submonomer method. Upon dissolution in water at pH = 9, the amphiphilic peptoids self-assemble into small spherical micelles having hydrodynamic radius in ∼5-10 nm range and critical micellar concentration (CMC) in the 0.034-0.094 mg/mL range. Small-angle neutron scattering (SANS) analysis of the micellar solutions revealed unprecedented dependence of the micellar structure on the number and position of ionic monomers along the chain. It was found that the micellar aggregation number ( Nagg) and the micellar radius ( Rm) both increase as the ionic monomer is positioned progressively away from the junction of the hydrophilic and hydrophobic segments along the polymer chain. By defining an ionic monomer position number ( n) as the number of monomers between the junction and the ionic monomer, Nagg exhibited a power law dependence on n with an exponent of ∼1/3 and ∼3/10 for the respective singly and triply charged series. By contrast, Rm exhibited a weaker dependence on the ionic monomer position by a power law relationship with an exponent of ∼1/10 and ∼1/20 for the respective singly and triply charged series. Furthermore, Rm was found to scale with Nagg in a power-law relationship with an exponent of 0.32 for the singly charged series, consistent with a weakly charged ionic star-like polymer model in the unscreened regime. This study demonstrated a unique method to precisely tailor the structure of small spherical micelles based on ionic block copolymers by controlling the sequence and position of the ionic monomer.

Pluronic®-bile salt mixed micelles.

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

Disassembly of Multicompartment Polymer Micelles in Spatial Sequence Using an Electrostatic Field and Its Application for Release in Chronological Order

AbstractMulticompartment micelles (MCPs), comprising sequences of repeated elemental discoid parts connected by fasciculus, were formed by self‐assembly of polystyrene‐block‐poly(2‐vinyl pyridine)‐block‐poly(ethylene oxide). Using an electrostatic field, the MCPs can be disassembled through consequent release of small spherical micelles. During this disassembly process, release of loaded species can be achieved from the micelles in chronological order. Two location‐selected cargos (mitoxantrone (MTNT) and fluorescein isothiocyanate (FITC)) in the outer and inner compartments of the micelles can be released in chronological order. Under the applied electrostatic field (intensity: 16 kV cm−1), the loaded MTNT was rapidly released with more than 80 % release, whereas the loaded FITC was slowly released with less than 20 % release in 12 h. At a later stage (after more than 12 h), the loaded MTNT was slowly released with less than 20 % release, while the loaded FITC was rapidly released with more than 80 % release.