Association and phase behavior of hydrophobically modified photoresponsive poly(acrylamide)s in the presence of ionic surfactant

 The extent of association between the cationic surfactant TTAB and a series of hydrophobically modified polyacrylamides (HPAMs) containing an N-n-alkyl and substituted azobenzene hydrophobic sidegroup has been studied utilizing a cationic surfactant-selective membrane electrode. Binding of TTAB to the polymer hydrophobes is found to increase with increasing hydrophobicity of the hydrophobe. In the presence of electrolyte, aqueous solutions of HPAMs and ionic surfactant exhibit an associative phase separation. The temperature or clearing point (CP) at which the system goes from a one phase to two-phase system are reported. The area of the two-phase region is found to increase with increasing electrolyte concentration, hydrophobicity of the hydrophobe for the high molecular weight HPAMs, and decreasing hydrophobicity for low molecular weight HPAMs. Exposure of HPAMs containing an azobenzene hydrophobe to UV light results in a decrease in interaction between the hydrophobe and surfactant and a corresponding decrease in the CP due to conversion of azobenzene from the more hydrophobic trans form to the less hydrophobic cis isomer. Received: 23 September 1996 Accepted: 11 March 1997     

Phase separation in aqueous mixtures of hydrophobically modified cellulose derivatives with their nonmodified analogues

Mixtures of hydrophobically graft-modified cellulose derivatives and their nonmodified analogues have been studied in aqueous solution. A qualitatively similar behavior was found in the phase behavior of nonionic as well as of cationic polymer systems. Over a large range of total polymer concentrations and mixture ratios the solutions phase separated into two phases of similar polymer concentration, with one of the phases enriched in the hydrophobically modified polymer. From the manufacturing process the cellulose derivatives investigated are likely to contain polymer chains with a rather continuous distribution in degrees of substitution and, possibly, substitution patterns. This causes a complex phase behavior that cannot be adequately described by a ternary representation. The multicomponent nature became apparent from composition analyses of the phases in equilibrium. It may thus be more appropriate to view the phase separation as a fractionation. A phase of small relative volume with a highly enhanced hydrophobe content (compared to the original hydrophobically modified polymer sample) was created. This was particularly obvious in more dilute solutions. Sometimes the phase separation was difficult to observe because the phases in equilibrium had similar polymer concentrations and, therefore, similar refractive indices. The observations presented here call for the attention of producers and users of these types of polymers. Received: 6 July 2000 Accepted: 6 September 2000     

Influence of hydrophobe content and salt concentration on dilute solution behaviour of hydrophobically modified ionic polymers from diallylammonium salts/sulfur dioxide cyclocopolymerization: Light scattering and fluorescence spectroscopy

Novel hydrophobically modified polyelectrolytes were synthesized using the cyclocopolymerization of sulfur dioxide, N,N-diallyl-N-carboethoxymethylammonium chloride and the hydrophobic monomer N,N-diallyl-N-octadecylammonium chloride. Aggregation of these polymers in aqueous solutions was characterized in the dilute regime by static light scattering and fluorescence spectroscopy as a function of hydrophobe content and NaCl concentration. Copolymers were observed to associate at very low concentrations (0.005 wt%). The copolymer is capable of associating at this very low polymer concentration because of the extended length of the hydrophobic monomer (C₁₈) that can reach far enough from the backbone to avoid electrostatic repulsion. Aggregation of the polymers increased with increasing hydrophobe content. Upon addition of salt, the apparent molecular weight of polymer aggregates decreased as a result of neutralization of the charges. At high salt concentrations, the size of the polymer aggregates was observed to increase again as a result of increased polarity of the solvent that resulted in more hydrophobic association.     

The Level of Hydrophobic Substitution and the Molecular Weight of Amphiphilic Poly-L-lysine-Based Polymers Strongly Affects Their Assembly into Polymeric Bilayer Vesicles

With the aim of producing new materials for drug and gene delivery, the variables associated with the preparation of poly-L-lysine-based vesicles were investigated. Amphiphilic poly-L-lysine graft copolymers with varying levels of grafted methoxypolyethylene glycol (mPEG) and palmitic acid were synthesized using two-step grafting reactions of the macromonomer, mPEG-p-nitrophenyl carbonate (mPEG, MW=5,000), and palmitic acid N-hydroxysuccinimide ester onto poly-L-lysine hydrobromide (MW=4,000 and 19,600). Polymers were characterized by gel permeation chromatography/light scattering. (1)H NMR, and an assay for unreacted varepsilon-amino groups. Polymeric unilamellar vesicles were produced by probe sonication of the amphiphilic poly-L-lysine-based polymers in the presence of cholesterol. Vesicles were characterized by electron microscopy and photon correlation spectroscopy. Vesicle formation was favored by a low molecular weight and a low level of palmitoyl substitution. A vesicle formation index has been derived, F ~ H/L DP, where H is the %molar level of unreacted L-lysine units, L is the %molar level of substituted palmitoyl units, and DP is the square root of the degree of polymerization of the polymer. Additionally, the size of these vesicles may be controlled by controlling the initial molecular weight of the parent poly-L-lysine/resulting amphiphilic polymer. Hence, amphiphilic poly-L-lysine-based polymers of molecular weight=89,000 and 25,000 produced polymeric vesicles of z-average mean diameter 570 nm and 252 nm, respectively. Vesicle encapsulation efficiency for the hydrophilic macromolecule, fluorescein isothiocyanate-dextran (MW=4,400), increased with vesicle size. Copyright 2001 Academic Press.     

Network formation of catanionic vesicles and oppositely charged polyelectrolytes. Effect of polymer charge density and hydrophobic modification

In nonequimolar solutions of a cationic and an anionic surfactant, vesicles bearing a net charge can be spontaneously formed and apparently exist as thermodynamically stable aggregates. These vesicles can associate strongly with polymers in solution by means of hydrophobic and/or electrostatic interactions. In the current work, we have investigated the rheological and microstructural properties of mixtures of cationic polyelectrolytes and net anionic sodium dodecyl sulfate/didodecyldimethylammonium bromide vesicles. The polyelectrolytes consist of two cationic cellulose derivatives with different charge densities; the lowest charge density polymer contains also hydrophobic grafts, with the number of charges equal to the number of grafts. For both systems, polymer-vesicle association leads to a major increase in viscosity and to gel-like behavior, but the viscosity effects are more pronounced for the less charged, hydrophobically modified polymer. Evaluation of the frequency dependence of the storage and loss moduli for the two systems shows further differences in behavior: while the more long-lived cross-links occur for the more highly charged hydrophilic polymer, the number of cross-links is higher for the hydrophobically modified polymer. Microstructure studies by cryogenic transmission electron microscopy indicate that the two polymers affect the vesicle stability in different ways. With the hydrophobically modified polymer, the aggregates remain largely in the form of globular vesicles and faceted vesicles (polygon-shaped vesicles with largely planar regions). For the hydrophilic polycation, on the other hand, the surfactant aggregate structure is more extensively modified: first, the vesicles change from a globular to a faceted shape; second, there is opening of the bilayers leading to holey vesicles and ultimately to considerable vesicle disruption leading to planar bilayer, disklike aggregates. The faceted shape is tentatively attributed to a crystallization of the surfactant film in the vesicles. It is inferred that a hydrophobically modified polyion with relatively low charge density can better stabilize vesicles due to formation of molecularly mixed aggregates, while a hydrophilic polyion with relatively high charge density associates so strongly to the surfactant films, due to strong electrostatic interactions, that the vesicles are more perturbed and even disrupted.     

新型疏水缔合聚合物P(AM/POEA)与表面活性剂的相互作用

采用粘度法、荧光探针和透射电镜研究了新型疏水缔合聚合物P(AM/POEA)和表面活性剂SDS和CTAB在水溶液中的相互作用. 聚合物P(AM/POEA)结构中, 疏水体(2-苯氧乙基丙烯酸酯)呈嵌段状无序地分布在聚丙烯酰胺主链上. 这类聚合物很容易和表面活性剂相互作用, 通过疏水缔合, 形成混合胶束状聚集体, 导致溶液粘度剧增. 随聚合物溶液中SDS的加入, 溶液粘度发生大幅度起伏变化, 出现最大值. 粘度最大值对应的表面活性剂浓度c_S,max位于表面活性剂CMC附近, 并发现它的位置不随聚合物微结构而变化. 然而它们缔合作用的增粘程度却与聚合物疏水体含量X_H及疏水嵌段尺寸N_H有关. 在实验浓度范围内, X_H和N_H愈大, 溶液的粘度越高. 此外用透射电镜直接观察到聚合物/表面活性剂体系中聚集体的交联结构形貌.     

Atom transfer radical polymerization of n‐butyl methacrylate in an aqueous dispersed system: A miniemulsion approach

Ultrasonication was applied in combination with a hydrophobe for the copper‐mediated atom transfer radical polymerization of n‐butyl methacrylate in an aqueous dispersed system. A controlled polymerization was successfully achieved, as demonstrated by a linear correlation between the molecular weights and the monomer conversion. The polydispersities of the polymers were small (weight‐average molecular weight/number‐average molecular weight < 1.5). The influence of several factors, including ultrasonication, the amount of the surfactant, and the nature of the initiator, on the polymerization kinetics, molecular weight, and particle size was studied. The polymerization rate and molecular weights were independent of the number of particles and only depended on the atom transfer equilibrium. The final particle size, however, was a function of all the parameters. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 4724–4734, 2000     

Slow Reorganization of Small Phosphatidylcholine Vesicles upon Adsorption of Amphiphilic Polymers

Static or dynamic light scattering measurements were performed in parallel, on dilute mixtures of DPPC/DPPA vesicles (typical radius 60 nm) and hydrophobically modified polymers. This technique gave evidence of the slow kinetics involved in both the reorganization of an adsorbed polymer layer and the membrane breakage. Hours, or sometimes days, were required in order to follow the variation of both the hydrodynamic radius and the scattering intensity at intermediate stages. Images of the intermediate species were collected using freeze-fracture electron microscopy (FFEM). Comparison of different polymers (of varying molecular weight or structure) revealed the prime importance of hydrophobicity on the disruption of membranes. Although the presence of a few percent of pendant alkyl chains along the polymer backbone induced adsorption to membranes, only the association with the more hydrophobic ones (>25 mol% of pendant octyl groups) resulted in small mixed objects of micellar size (radius about 10 nm). The drop of the mean radius of intermediate structures formed upon the vesicle breakage was also sensitive to temperature. A tentative mechanism was proposed on the basis of kinetics and FFEM studies. Copyright 2001 Academic Press.     

Association of octyl-modified poly(acrylic acid) onto unilamellar vesicles of lipids and kinetics of vesicle disruption

Water-soluble polymers containing a few hydrophobic anchors are known to bind onto lipid vesicles and are used as stabilizers of liposome-based formulas. In contrast, polymers with high hydrophobicity destabilize the lipid bilayers. With macromolecules of intermediate hydrophobic/hydrophilic balance, a gradual sweep of the stabilization-destabilization capacity can be achieved and is considered as promising triggered systems for drug release, although the mechanism of permeabilization and membrane breakage using polymers is essentially conjectural to date. As a model system, we used short octyl-modified poly(acrylic acid)s (MW 8000 g/mol) sensitive to pH, temperature, and ionic strength in conjunction with small unilamellar vesicles mainly comprised of DPPC or egg-PC. Kinetics of vesicle fragmentation was followed using static and dynamic light scattering. Polymer adsorption was studied by nonradiative energy transfer between pyrene-labeled lipids and a naphthalene-modified polymer. The permeability of the vesicles was characterized by calcein leakage experiments. The key findings were (i) the lack of coupling between the density of bound polymer and the rate of disruption and (ii) the qualitative difference depending on whether the polymer contains or not isopropyl side groups. Point i relates to the increase of the rate of polymer adsorption with increasing bulk polymer concentration, while the breakage is essentially unaffected. Point ii relates to the stabilization of large membrane fragments (Stokes radius ca. 40 nm) in the presence of a polymer with no isopropyl side groups, while micelle-like assemblies (Stokes radius 8 nm) containing the lipids are obtained with an isopropyl-containing polymer of similar hydrophobicity. Both polymers display similar efficiency at disrupting small vesicles. The mechanism of polymer-induced disruption appears to differ markedly from the disruption steps now recognized for conventional (molecular) surfactant and is discussed on the basis of data obtained with different membrane fluidity, polymer structure, concentration, and hydrophilicity.     

新型疏水缔合丙烯酰胺/2-苯氧乙基丙烯酸酯共聚物的合成与性质

采用胶束共聚方法合成了一种新型的疏水缔合共聚物 ,它由丙烯酰胺 (AM)和少量的 2 苯氧乙基丙烯酸酯 (POEA) (<1 0mol% )组成 ,具有良好的水溶性 .当溶液浓度超过一定值c 后 ,由于分子间的疏水缔合 ,产生很大的增粘作用 .研究了不同聚合条件下包括单体浓度、投料比和SMR值对聚合物的结构和性能的影响 .实验结果表明 ,聚合物的粘度性质和缔合行为取决于其分子量的大小、疏水单体含量及其嵌段的长度和分布 .     

Effect of polymer characteristics on structure of polymer-liposome complexes

In the current study, we examined the effect of polymer characteristics on the structure of complexes formed between poly(methacrylic acid-co-n-alkyl methacrylate) and with phosphatidylcholine/cholesterol liposomes. We varied the polymer concentration in the vesicles, the preparation concentration of lipid and polymer components during preparation, the molecular weight of the polymer chain, the molecular weight of the polymer's hydrophobic side groups and their mole fraction. The vesicle behavior indicated polymer-free bilayers and bilayers complexed with polymer coexisted at low polymer concentrations. As the polymer concentration exceeds a critical level, however, the system became homogeneous, indicating bilayer uniformity of the bilayer. As the polymer content was raised, the vesicle size and fluidity increased, and the transition temperature decreased. We found that the vesicle size mostly affects the membrane fluidity. We also found that the thermal properties (transition temperature and the magnitude of heat capacity of the peak, DeltaCp) are governed by the effects of the polymer on the structure of bilayer. The length of the alkyl chain of the polymer is shown to significantly affect the structure of polymer-liposome complexes, as did the chain molecular weight and mole concentration of hydrophobic group in the polymer.     

Binding of surfactants to hydrophobically modified polymers

Recent progress in the understanding of the binding of surfactants to hydrophobically modified polymers (HMP), and the consequences of such binding, is reviewed. HMP are water-soluble polymers onto which low proportions of hydrophobic sidechains (hydrophobes) have been grafted. In an aqueous environment, the HMP hydrophobes associate among themselves and with added surfactant molecules into micelle-like aggregates. An HMP may therefore be considered as a ‘modified surfactant’, and the binding of surfactants to HMP is analogous to the mixed micellisation in mixed surfactant solutions. The binding isotherm gives the concentration of free (monomeric) surfactant and the stoichiometry of the HMP/surfactant complex at different total compositions. In mixtures involving ionic surfactants, it is found that the free surfactant often dominates, and gives important contributions to the ionic strength. Characteristic properties of HMP/surfactant mixtures may be related to stoichiometries of the mixed complexes. Thus, the maximum in solution viscosity, which is commonly found in HMP/surfactant mixtures, occurs at a similar hydrophobe stoichiometry (ratio of bound surfactant to HMP hydrophobe) for many different systems, although the total concentrations of surfactant at the maximum may vary by orders of magnitude, depending on the surfactant cmc. The solubility of a complex of oppositely charged HMP and surfactant is related to the charge stoichiometry of the complex. The phase separation/redissolution phenomena occurring in the bulk solution influence the HMP adsorption to surfaces and the forces between surfaces with adsorbed HMP.     

Polymer-surfactant and protein-surfactant interactions

The phase behavior and some physicochemical properties of homopolymers (HP) and hydrophobically modified (HMP) polymers, as well as of polyelectrolytes (PE) and proteins (PR), in the presence of aqueous surfactants, or their mixtures, are discussed. Mixing the above components gives rise to the formation of organized phases, whose properties are controlled by polymer and/or surfactant content, temperature, pH, and ionic strength. Depending on the nature, concentration, and net charge of both solutes, molecular solutions, polymer-surfactant complexes, adsorption onto micelles and vesicles, gels, liquid crystalline phases, and precipitates are observed. Such rich polymorphic behavior is the result of a complex balance between electrostatic, excluded volume, van der Waals, and other contributions to overall system stability. It is also modulated by the molecular details and architecture of both the polymer and the surfactant. Different experimental methods allow investigation of the above systems and getting information on the nature of polymer-surfactant interactions (PSI). Surface adsorption and thermodynamic methods, together with investigation of the phase diagrams, give information on the forces controlling PSI and on the existence of different phases. Conductivity, QELS and viscosity allow estimating the size and shape of polymer-surfactant (protein-surfactant) complexes. Optical microscopy, cryo-TEM, AFM, NMR, fluorescence, and relaxation methods give more information on the above systems. Use of the above mixtures in controlling gelation, surface covering, preparing dielectric layers, and drug release is suggested.     

Gel formation in systems composed of drug containing catanionic vesicles and oppositely charged hydrophobically modified polymer

The aim of this study was to explore if mixtures of drug containing catanionic vesicles and polymers give rise to gel formation, and if so, if drug release from these gels could be prolonged. Catanionic vesicles formed from the drug substances alprenolol or tetracaine, and the oppositely charged surfactant sodium dodecyl sulphate were mixed with polymers. Three polymers with different properties were employed: one bearing hydrophobic modifications, one positively charged and one positively charged polymer bearing hydrophobic modifications. The structure of the vesicles before and after addition of polymer was investigated by using cryo-TEM. Gel formation was confirmed by using rheological measurements. Drug release was studied using a modified USP paddle method. Gels were observed to form only in the case when catanionic vesicles, most likely with a net negative charge, were mixed with positively charged polymer bearing lipophilic modifications. The release of drug substance from these systems, where the vesicles are not trapped within the gel but constitute a founding part of it, could be significantly prolonged. The drug release rate was found to depend on vesicle concentration to a higher extent than on polymer concentration.     

丙烯酰胺和表面活性大单体共聚物的合成及其性能研究

首先合成表面活性大分子单体丙烯酸聚氧乙烯（２３）－十二烷基酯（ＡＡ－ＰＯＥＬＥ）,再通过与丙烯酰胺共聚合的方法得到在水溶性聚合物聚丙烯酰胺分子结构中引入疏水基团的共聚物改性ＰＡＭ。因ＡＡ－ＯＰＥＬＥ单体具有表面活性,所以共聚合时无需添加乳化剂。当改性ＰＡＭ中疏水基团含量为１．１０ｍｏｌ％时,其水溶液表现出独特的流变性和增稠性,着重讨论了改性ＰＡＭ作为乳胶增稠剂的性能。     

Topology change by screening the electrostatic interactions in a polymer–surfactant system

We show that a neutral polymer (PEG) induces a topology transition of the bilayers of an ionic surfactant system (SDS–hexanol–brine), provided that the electrostatic interactions between membranes are screened. Hexanol is used as a cosurfactant in order to get a lamellar or a sponge phase, depending on the cosurfactant/surfactant mass ratio. Using brine as solvent, the addition of polymer triggers a transformation between flat or saddle-like bilayers into vesicles. This modification is not observed in pure water because of the electrostatic repulsion between membranes. The effect can be understood in terms of the modification of the membrane Gaussian modulus due to polymer adsorption and of the entropy gain of the adsorbed polymer when the membrane bends to form a vesicle.     

Macromolecular crowding improves polymer encapsulation within giant lipid vesicles

We report the effect of macromolecular crowding on encapsulation efficiency of fluorescently labeled poly(ethylene glycol) (PEG) and dextran polymers within individual giant lipid vesicles (GVs). Low concentrations of the fluorescently labeled polymers (82 nM to 186 pM) were mixed with varying concentrations of nonfluorescent polymers that served as crowding agents during vesicle formation by gentle hydration. Encapsulation efficiency of the fluorescently labeled polymers in individual GVs (EEind) was determined via confocal fluorescence microscopy. EEind for high molecular weight polymers (e.g., fluorescein isothiocyanate (FITC)-dextran 500 and 2000 kDa) increased substantially in the presence of several weight percent unlabeled PEG or dextran. For example, when 0.24 microM FITC dextran 500 kDa was encapsulated, addition of 3% PEG 8 kDa improved the mean concentration in the GVs from 0.14 microM (+/-50%) to 0.24 microM (+/-12%). Light scattering data indicate reduced hydrodynamic radii for polymers as a function of increasing polymer concentration, suggesting that the improvements in EEind result from polymer condensation due to macromolecular crowding. Polymeric cosolutes did not significantly impact EEind for lower molecular weight polymers (e.g., Alexa Fluor 488-PEG 20 kDa), which already encapsulated efficiently (EEind to approximately 1). However, for both the higher and lower molecular weight labeled polymers, cosolutes led to improved uniformity in EEind for vesicles within a batch. Methods for improving the value and homogeneity of EEind for polymeric solutes in lipid vesicles are important in a variety of applications, including the use of vesicles as microreactors and as vehicles for drug delivery.     

LDH as Nanofiller: Organic Modification and Dispersion in Polymers

Summary: Layered double hydroxide (LDH) is a relatively new class of layered crystalline clay materials to be used as nanofiller in various polymer matrices. We report here the organic modification of LDH by anionic surfactants having different sizes and functionalities. Subsequently, their dispersion in polymer is discussed and finally the characteristics of the polymer/LDH nanocomposites are investigated. LDH has been modified using regeneration method, which shows that irrespective of size and functionality of the anionic surfactant, organic modification can be carried out efficiently. However, it has been observed that alkyl sulfonate are more efficiently intercalated within LDH layers than other surfactants giving well defined crystal structure of the modified LDH. These modified LDH, when dispersed in polymers like maleic anhydride grafted polyethylene shows that not only the size of the surfactant, but also the functionality of the surfactant influences their dispersion in a non polar polymer matrix.     

选择性膜电极研究表面活性剂与大分子的相互作用

结合本实验室的工作介绍了表面活性剂选择性膜电极研究表面活性剂与大分子相互作用的实验装置和原理,并综述了表面活性剂选择性膜电极在研究离子型表面活性剂及其二元混合体系与不同类型大分子之间相互作用中的应用.讨论了大分子的分子量、外加盐和表面活性剂的结构对表面活性剂和大分子之间相互作用的影响结果.