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A kinetic study was carried out to monitor the time-dependent formation of surfactant-stabilized polymeric nanoparticles prepared by controlled phase separation. The nanoparticles were made of poly(methylmethacrylate) or polystyrene and several ionic and nonionic surfactants. The dispersion was prepared by fast mixing a solution of the polymers in organic solvents with a solution of a surfactant in water. We observed the formation of well-defined nanoparticles measured by time-resolved small-angle x-ray scattering (TR-SAXS). Our results suggest that the kinetics for the formation of nanoparticles comprising ionic surfactants is much faster (in the range of milliseconds) than that for nanoparticles comprising nonionic surfactants (on the time scales of several seconds). We were able to observe the transformation of particle surface from transient structure to hard sphere one in real time. Some systems manifest a plethora of structural changes that demands further experimental research.

Stable polymeric nanoparticles were prepared by self-assembly of poly(ethylacrylic acid) homopolymers. The mechanism of the self-assembly is based on heating a solution of thermoresponsive partiall...

A new approach to polymer self-assembly is presented where stable polymeric nanoparticles are formed from homopolymers of one type only and without any assembly triggering additives. The mechanism of the self-assembly is based on the following idea. A thermosensitive polymer solution is heated, the solvent quality gradually worsen upon heating and polymer―polymer contacts are preferred over polymer―solvent contacts, which leads to the formation of polymer assemblies. Upon subsequent cooling to laboratory temperature, the assemblies should eventually dissolve, however, this is not the case due to the fact that polymer chains brought to a close proximity at elevated temperatures become hydrogen-bonded. In addition, hydrogen bonds strengthen upon cooling. As a result, stable nanoparticles are obtained. This mechanism is illustrated on poly(ethylacrylic acid) (PEA) homopolymers, which create a thermoresponsive system at certain degrees of ionization. Nanoparticles are resistant to agglomeration and macroscopic phase separation during heating as well as upon cooling down. The size of nanoparticles can be monitored during the growth and custom-tailored by tuning critical parameters, especially the temperature and time of heating. Nanoparticles are stable over long periods of time. They are stable in a broad range of salt concentrations, including physiological conditions, and possess a mild acceptable degree of polydispersity. Investigation of PEA solution properties, monitoring of the self-assembly process as well as a detailed characterization of nanoparticles were performed by static, dynamic, and electrophoretic light scattering. A comparison with the most related polymers (poly(methacrylic acid) and poly(propylacrylic acid)) was also performed.

New, hydrophilic polymers and copolymers based on HPMA, carrying reactive thiazolidine-2-thione groups either situated at the polymer chain end or randomly distributed along the chains bound to the polymer backbone via spacers containing reductively degradable disulfide linkages, have been developed for an efficient and intracellularly removable coating of gene-delivery vectors. Amino-group-bearing PS-latex nanoparticles and self-assembled poly(L-lysine)/DNA complexes were used as models for gene-delivery viral and nonviral vectors to study the coating reaction with reactive HPMA-based (co)polymers. It is shown that modification of the particles was effective, resulting in an increase in the M w and R h of the particles, which depend on the polymer length and its detailed structure. Incubation of the coated particles in buffers modeling the intracellular environment induced unshielding of the vectors and release of the polymer layer from their surface.

It is shown that very pure sodium hyaluronate (HA) contains small amounts of strongly scattering impurities not detectable on mass scale by refractometric detection, but clearly detectable using low angle light scattering detection during a static bulk light scattering experiment. Size filtration of its solutions does not remove these impurities, only reduces their amount depending on filter porosity. Complete removal of these particle impurities, independent of filter porosity, is achieved by hydrophobic adsorption on hydrophobic filter membranes. Using 0.1 M NaCl as a mobile phase, size exclusion chromatography (SEC) column removes the impurities by hydrophobic adsorption as well; molar masses obtained from both techniques thus agree when hydrophobic filters are used in bulk light scattering experiments. Diverse hydrodynamic flow retardation effects including slalom chromatography behavior are shown to substantially bias molar mass distributions obtained for ultra-high molar mass (UHM) HA, unle...

Various conjugates of anticancer drug doxorubicin (Dox) covalently bound by the hydrolytically degradable hydrazone bond to the drug carrier based on N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers were synthesised. Structure of the conjugates differed in the type and the content of hydrophobic substituent (dodecyl, oleic acid and cholesterol moieties) introduced into the polymer structure. In aqueous solutions the conjugates self-assembled into high-molecular-weight supramolecular structures, such as polymeric micelles or stable hydrophilic nanoparticles 13-37 nm in diameter, depending on the type and the content of hydrophobic substituents. Treatment of mice bearing EL-4 T cell lymphoma with the conjugates in the therapeutic regime of drug administration (i.v.) resulted in significant tumour regression with up to 100% of long-term survivors, depending on the dose and the detailed structure of the carrier. The nanoparticles formed by the conjugate bearing cholesterol moiety exhibited prolonged blood circulation and enhanced tumour accumulation indicating an important role of the EPR effect in excellent anticancer activity of the conjugate.

A new pathway for the synthesis of HPMA graft copolymers was developed and their self-assembly into hybrid hydrogels was investigated. Linear water-soluble polyHPMA was chosen as the polymer backbone, whereas coiled-coil forming peptides, covalently attached to the backbone, formed the grafts. Peptides of different chain lengths were chosen for evaluation. The results revealed that graft length greatly affected gelation ability. At least four heptads were needed to facilitate the hybrid system to form hydrogels under the experimental conditions used. The major factors affecting the kinetics of hydrogel self-assembly were concentration and temperature.

The time course of self-assembly of a hybrid hydrogel system was investigated using dynamic light scattering (DLS) techniques. The self-assembling system consisted of a hydrophilic synthetic N-(2-hydroxypropyl)methacrylamide (HPMA) polymer backbone and a pair of oppositely charged peptide grafts (CCE and CCK). These two distinct pentaheptad peptides were anticipated to act as physical cross-linkers by the formation of antiparallel coiled-coil heterodimers. Equimolar mixture of HPMA graft copolymers CCE-P and CCK-P solutions (where P is the HPMA copolymer backbone) with total concentration from 1.25 to 10 mg/mL were measured at a scattering angle 90 degrees and room temperature. A critical extension of average relaxation time was observed with increasing concentration and incubation time. To reveal the role of coiled-coil grafts in the self-assembly process, a pair of modified random coil peptides, CCEw and CCKy, was designed. The DLS evaluation of HPMA copolymer conjugates (CCEw-P and CCKy-P) at total concentration of 10 mg/mL demonstrated that no association occurred after 28 h of incubation. Moreover, addition of a competing peptide (CCK) or a denaturant (guanidium chloride, GndHCl) to the self-assembled CCE-P/CCK-P hydrogels resulted in partial disassembly or collapse of the hydrogel clusters. These results correlated to changes in the secondary structure of peptides (grafts) as measured by circular dichroism spectroscopy (CD). These investigations supported the hypothesis that the self-assembly of CCE-P/CCK-P into hybrid hydrogels is mediated by the formation of coiled-coil heterodimers.

New method of synthesis of water-soluble polymer-drug conjugates, exhibiting remarkable anticancer activity in mice models, has been developed. In the conjugates, an anticancer drug doxorubicin (DOX) is attached to a polymer carrier based on N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer via a hydrolytically labile hydrazone bond. New methacrylamide-type comonomers, containing either hydrazide group or hydrazon of DOX, were used for copolymerization with HPMA. In contrast to the synthetic procedure described earlier the new method is simpler, cheaper, and results in a better-defined conjugate structure. The conjugates are fairly stable in buffer at pH 7.4 (model of blood stream) but release DOX under mild acid conditions modeling the tumor microenvironment. The conjugates showed significant in vivo antitumor activity in treatment of T-cell lymphoma EL-4 bearing mice with up to 100% long-term survivors. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008

pH-sensitive micelles formed by interchain hydrogen bonding of poly(methacrylic acid)-block-poly(ethylene oxide) copolymers were prepared and investigated at pH < 5. Both M w and R h of the micelles increase with decreasing pH of the solution, displaying an asymptotic tendency at low pH values. The observed micelles are well-defined nanoparticles with narrow size distributions (polydispersity ΔR h /R h ≤ 0.05) comparable with regular diblock copolymer micelles. The CMCs occur slightly below c=1×10 -4 g.mL -1 . The micelles are negatively charged and their time stability is lower than that of regular copolymer micelles based purely on hydrophobic interactions.

Two hydrophilic polymer systems, multivalent N-(2-hydroxypropyl)methacrylamide-based copolymers bearing thiazolidine-2-thione (TT) reactive groups randomly distributed along the polymer chain and monovalent semitelechelic pHPMA with the TT end group, were designed for surface modification of gene delivery vectors, namely, DNA polyelectrolyte complexes (PECs) and adenoviruses. In this study, the amino group-modified polystyrene latex nanoparticles were selected as a suitable model of a nanoparticulate delivery system bearing NH2 groups on the surface. The coating process was monitored by changes in molecular weight and hydrodynamic parameters of the nanoparticles by light scattering methods. It was shown that for study of the coating process the model latex particles are more suitable than the original PEC vectors due to better chemical and physical stability of latexes. The results obtained in the model study (reaction conditions, methods of evaluation) suggest an optimal polymer structure and a method of efficient and complete coating of nanoparticle surface well applicable to the real gene delivery vectors.

Solutions of poly(N-isopropylacrylamide) (PNIPA) with ionic and nonionic surfactants were investigated by light scattering methods at temperatures 15–45 °C. In contrast to previous studies, where surfactants were used in excess, lower concentrations of surfactants were used. The formation of well-defined nanoparticles of PNIPA was observed on heating above the lower critical solution temperature. The effect of PNIPA and surfactant concentrations, and molecular weight of PNIPA on nanoparticle parameters and on the phase transition temperature of PNIPA solutions were investigated. An interpretation based on stabilization of PNIPA nuclei by surfactants was suggested.

Short polypeptides with four pentad repeats, (VPGVG)(4) and (VPAVG)(4), were synthesised by manual fluorenylmethoxycarbonyl/tert-butyl (Fmoc/t-Bu) solid phase peptide synthesis using a convergent approach. In the next step, the peptides were coupled via their N-terminus with activated semi-telechelic poly(ethylene glycol) O-(N-Fmoc-2-aminoethyl)-O'-(2-carboxyethyl)undeca(ethylene glycol) (Fmoc-PEG-COOH) to yield monodisperse Fmoc-PEG-peptide diblock copolymer. Both the presence of the terminal hydrophobic Fmoc group and the hydrophilic PEG chain in the copolymers were shown to play a crucial role in their self-associative behaviour, leading to reversible formation of supramolecular thermoresponsive assemblies. The peptides and their PEG derivatives were characterised by HPLC, NMR and MALDI-TOF MS. The associative behaviour of the peptides and their PEG derivatives was studied by dynamic light scattering, MAS NMR and phase contrast microscopy. [image: see text]

Poly(adipoyl chloride-alt-cystamine) nanoparticles covalently coated with poly(ethylene oxide) (M w = 2,000 or 5,000) were prepared as a model of glutathione-degradable drug, protein, or deoxyribonucleic acid delivery systems. The polyamide forming the micellar core has disulfide bonds in the main chain and thus its degradation gives low molecular weight products. The degradation of nanoparticles by the action of glutathione in the reduced or oxidized forms was monitored by time dependencies of the light scattering intensity at 37 °C in media modeling intracellular environment. The lifetimes of nanoparticles were determined. The reductive degradation of the nanoparticles by the reaction with reduced glutathione is an order of magnitude faster than their spontaneous degradation. The effect of nanoparticle concentration and solution pH was also investigated.

Solutions of poly(N-isopropylacrylamide) (PNIPA) with added sodium dodecyl sulfate (SDS) were investigated by light scattering methods at temperatures of 15-40°C. The formation of well-defined nanoparticles of PNIPA was observed on heating at low SDS additions. The effects of PNIPA and SDS concentrations and the molecular weight of PNIPA on nanoparticle parameters were investigated. An interpretation based on stabilization of PNIPA nuclei by SDS was suggested.

The size, aggregation number and other quantities which characterize the formation of micelles in a bidisperse solution of block copolymers which are chemically identical but have different block asymmetries has been studied in a selective solvent using LS and SANS techniques. Experimental results for the comicellization of two chemically identical block copolymers (high molecular weight, PS-PI, and a low molecular weight dPS-PI with a deuterated PS block) and two slightly incompatible copolymers (high molecular weight PS-HPI, and dPS-PI) in decane, a selective solvent for PI, are reported. Individually, each of the PS-HPI and PS-PI copolymers formed micelles with a PS core, which were stable over the entire temperature range covered by the experiments (25-70°C). The small copolymer, dPS-PI, formed micelles with a highly swollen core at low temperatures and was molecularly dispersed above the critical micelle temperature (47 °C). Comicellization was observed for both pairs of copolymers studied over a broad range of mixing ratios. The mixed micelles were comprised of large copolymer (PS-HPI or PS-PI) and a portion of the small copolymer (dPS-PI). The amount of adsorbed dPS-PI copolymer increased with increasing weight fraction of this copolymer and decreased with increasing temperature. The critical comicellization temperature was estimated as 70 and 60 °C for the comicelles based on PS-HPI and PS-PI copolymers, respectively. The SANS data suggest that the small copolymer does not form a shell coating the PS core of the initial micelle, but is instead incorporated into the core where it forms a layer of mixed dPS and PS chains.

Multishell particles were prepared by γ-radiation-induced polymerization of methyl methacrylate (MMA) in polystyrene-block-poly(methacrylic acid) (PS-b-PMA) aqueous micellar solution and their structure was studied by small-angle neutron scattering (SANS). Before polymerization, almost all MMA molecules are distributed in aqueous phase and only 1% of MMA is accumulated inside the micelles. The newly formed polymer (PMMA) is deposited on the surface of PS cores of the original micelles. The effect of the MMA concentration, micelle concentration, absorbed radiation dose, and absorbed dose rate on the characteristics of the resulting particles was examined. The thickness of the PMMA shell (20-218 A for the presented series of samples) can be easily controlled by variation of monomer and/or micelle concentration. Universal plots of the core volume (PS+PMMA) and SANS curve were presented. These plots facilitate choosing proper monomer and micelle concentrations and detecting possible irregularities in the parameters of the resulting particles.

Dynamic light scattering was used to investigate the dynamics of sodium poly(styrene sulfonate) and fully neutralized poly(acrylic acid) gels as a function of the degree of swelling and weight ratio of cross-linking agent. It was shown that the collective diffusion coefficient increases with increasing degree of swelling and that the diffusion coefficient shows stronger concentration dependence than predicted by scaling arguments. For gel samples measured at the swelling equilibrium, the diffusion coefficient increases with increasing gel concentration for both gel systems.

A novel polymeric micellar pH-sensitive system for delivery of doxorubicin (DOX) is described. Polymeric micelles were prepared by self-assembly of amphiphilic diblock copolymers in aqueous solutions. The copolymers consist of a biocompatible hydrophilic poly(ethylene oxide) (PEO) block and a hydrophobic block containing covalently bound anthracycline antibiotic DOX. The starting block copolymers poly(ethylene oxide)-block-poly(allyl glycidyl ether) (PEO-PAGE) with a very narrow molecular weight distribution (Mw/Mn ca. 1.05) were prepared by anionic ring opening polymerization using sodium salt of poly(ethylene oxide) monomethyl ether as macroinitiator and allyl glycidyl ether as functional monomer. The copolymers were covalently modified via reactive double bonds by the addition of methyl sulfanylacetate. The resulting ester subsequently reacted with hydrazine hydrate yielding polymer hydrazide. The hydrazide was coupled with DOX yielding pH-sensitive hydrazone bonds between the drug and carrier. The resulting conjugate containing ca. 3 wt.% DOX forms micelles with Rh(a)=104 nm in phosphate-buffered saline. After incubation in buffers at 37 degrees C DOX was released faster at pH 5.0 (close to pH in endosomes; 43% DOX released within 24 h) than at pH 7.4 (pH of blood plasma; 16% DOX released within 24 h). Cleavage of hydrazone bonds between DOX and carrier continues even after plateau in the DOX release from micelles incubated in aqueous solutions is reached.

We have examined solutions of a polystyrene-polybutadiene pentablock copolymer in n-heptane, a strongly selective solvent for polybutadiene. Small angle neutron scattering from 7 to 15% samples reveals domains about 10 nm in radius formed by the association of ∼200 polystyrene blocks. Dynamic light scattering measurements on 8 and 9% samples showed three modes: a fast diffusive mode related to the collective diffusion in semidilute solutions/gels; a relaxational mode related to the local dynamics of polystyrene domains trapped in the gel formed by bridging the domains with the polybutadiene chains; and a very slow diffusive mode. The relaxational dynamics persisted over the entire temperature range, becoming faster with increasing temperature, indicating a decreased microviscosity at higher temperatures. The slow dynamics seems to be connected with heterogeneities in the physical gel due to microsyneresis and almost disappeared above 50 °C. Macroscopic phase separation into two liquid phases was observed in a dilute solution of the un-associated copolymer, and into a liquid and gel phase at higher concentrations. The absence of flower-like micelles in dilute solutions and the macroscopic phase seperation suggest that the gels in the pentablock are formed by random association of multiplet domains and not by bridging of micellar domains.

Novel diblock copolymers designed for the preparation of micellar drug delivery systems, consisting of hydrophobic poly(allyl glycidyl ether) (PAGE) and hydrophilic poly(ethylene oxide) (PEO), were prepared, and their self-assembly into micellar structures was studied. Copolymers differing in the length of the polymer blocks were purified and characterized. These amphiphilic copolymers with narrow molecular weight distributions were prepared through the anionic polymerization of allyl glycidyl ether with PEO monomethyl ether sodium salt as the macroinitiator. The PAGE–PEO copolymer readily formed small micelles with narrow size distributions via simple dissolution in water. The addition of pendant double bonds to the hydrophobic part of the chain was intended for further covalent modifications. Catalytic hydrogenation, the radical crosslinking of the micelle core, and the addition of thiol to double bonds of the copolymer were examples of such modifications that were proved to proceed with a quantitative yield for this copolymer. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 95: 201–211, 2005

Summary: The exchange of sodium polymethacrylate (Na-PMA) for anionic surfactant sodium dodecylsulfate (SDS) in a polyelectrolyte complex of Na-PMA and poly(L-lysine) (PLL) was studied by light scattering techniques. The exchange reaction proceeds inside the complex particles without any aggregation. It causes swelling of the particles and the formation of thick polymer shell around them. In order to prove the formation of the shell, the colloidal stability of the particles in salt solutions was studied. The addition of SDS to a complex solution dramatically increases colloid stability. The stability was found to be independent of the mixing ratio of the initial complex, depending only on the molecular weight of Na-PMA and slowly decreasing with time. The mechanism of the exchange reaction was proposed. The addition of SDS causes fast substitution of charged units of Na-PMA for surfactant molecules in the complex and formation of the PLL/SDS complex stabilized by hydrophobic interactions between aliphatic chains of SDS. The Na-PMA chains cannot be released sufficiently fast from the particles due to entanglements of the chains inside the particles. They build a thick stabilizing shell around the particles and lead to their swelling. This shell protects the particles against coagulation at relatively high salt concentrations. However, such state of the particles does not correspond to thermodynamic equilibrium. Na-PMA is very slowly released from the particles, decreasing the density of stabilizing shell and stability of the particles in salt solutions. The possible application of ternary conjugates in drug delivery is discussed. Schematic representation of changes in structure and stability of Na-PMA/PLL complex particles upon the exchange of polyanion Na-PMA for negatively charged surfactant SDS.

The kinetics of the disorder−order transition (ODT) in a triblock of polystyrene (PS) and poly(ethylene-co-butylene) (PEB), in mineral oil, a selective solvent for the middle PEB block, was followed by time-resolved SAXS using both temperature ramp and rapid temperature quench techniques. Data analysis, using the Percus−Yevick interacting hard-sphere model plus Gaussians for the Bragg peaks in the ordered body-centered-cubic (bcc) state, shows that the core radius Rc, the hard-sphere volume fraction φ, and their interaction radius Rhs increased with decreasing temperature in the disordered state. At the ODT, φ reaches a maximum and Rc and φ change on ordering. The kinetics exhibits two stages corresponding to temperature equilibration and supercooling of the micellar fluid followed by nucleation and growth of the ordered state. The induction time for the onset of the second stage shows a minimum around the glass transition of the polystyrene cores.

Synthetic gene delivery vectors based on polyelectrolyte complexes of nucleic acids and polycations are widely studied as safe substitutes of viral vectors. Here, we synthesized a series of thermor...

Comicellization of a diblock block copolymer polystyrene-block-hydrogenated polyisoprene, PS-HPI (M w 1.05 x 10 5 g mol -1 , the weight fraction of styrene wps 0.34), and triblock copolymer polystyrene-block-hydrogenated polybutadiene-block-polystyrene, PS-HPB-PS (M w 7.0 x 10 4 g mol -1 , ω PS 0.28), in selective solvents was investigated by static and dynamic light scattering methods at 25-70 °C. Decane was a selective solvent for HPI and HPB blocks and 1,4-dioxane for PS blocks. HPI and HPB blocks are incompatible. Only the diblock copolymer formed micelles in decane while the triblock was molecularly dissolved at low concentrations and the measurement temperatures. Both the copolymers formed micelles of different sizes in 1,4-dioxane solutions. Comicellization was observed at all weight fraction of PS-HPB-PS, X, in solutions of copolymer mixtures in both solvents. In contrast to mixtures of chemically identical diblock copolymers with different molecular weights of the constituent blocks in selective solvents, small changes of micellar parameters resulting from comicellization were found in the copolymer mixtures under study. This is due to different constitution of the copolymers and their partial incompatibility. The X dependence of the molecular weight and size of comicelles in decane at low values ofXwas successfully described by adsorption of the PS-HPB-PS copolymers on micelles of the PS-HPI copolymer. The large PS-HPI copolymers were accommodated in small micelles of the PS-HPB-PS copolymer in 1,4-dioxane solutions with an excess of the PS-HPI.

We have used small-angle x-ray scattering (SAXS), and small-angle neutron scattering (SANS) to study the micelle structure of a polystyrene-block-poly(ethene-co-butene)-block-polystyrene triblock copolymer in dilute - semidilute solutions in solvents selective for either the outer styrene block (dioxane) or for the middle block (heptane or tetradecane) Measurements of equilibrium structure factors showed that micelles were formed in both types of selective solvents. In the case of dioxane, the micelles are isolated whereas in the case of heptane or tetradecane, a bridged micellar structure may be formed at higher copolymer concentrations. In both cases we observed an ordered cubic structure of insoluble domains (micellar cores) at high concentrations (> 8 %). The micellar scattering function was fit to the Percus-Yevick interacting hard-sphere model The temperature dependence of the core radius, the hard-sphere interaction radius and the volume fraction of hard spheres were obtained We also used synchrotron-based time-resolved SAXS to examine the kinetics of ordering of the micelles on a cubic lattice for many different temperature jumps into the ordered cubic phase starting from the disordered micellar fluid phase in different solvents at different concentrations. The time evolution of the structure changes was determined by fitting the data with Gaussians to describe the structure factor of the ordered Bragg peaks and the Percus-Yevick structure factor was used to describe the micellar fluid. The time dependence of the peak intensities and widths as well as of the micellar parameters will be presented The results showing the kinetics of the transformation from the fluid to the ordered phase were analyzed using the Mehl-Johnson-Avrami theory of nucleation.

Suitable experimental techniques and theoretical deconvolution and simulation procedures applicable to determination of concentration profiles of paramagnetic particles by ESRI technique and for subsequent determination of diffusion coefficients of paramagnetic tracers in the sample were proposed. The macroscopic diffusion coefficients, D, of paramagnetic tracers in cross-linked 2-hydroxyethyl methacrylate (HEMA) gels equilibrium-swollen with methanol and in polyHEMA methanolic solutions were measured by one-dimensional electron spin resonance imaging (1D ESRI). Both types of the matrix were characterized by dynamic correlation length, Lh, determined by dynamic light scattering (DLS). The dependence of diffusion coefficients on concentration of polyHEMA in methanolic solutions was well fitted within both Phillies' and Petit's models at approximately the same level of accuracy. A slower diffusion of the tracers was found in HEMA gels compared with the solution containing the same concentration of polyHEMA ...

Three diblock copolymers of poly[ N -(2-hydroxypropyl)methacrylamide] (poly(HPMA)) and poly( n -butyl acrylate) (poly(BA)) with varying lengths of blocks were prepared by atom transfer radical polymerization. All copolymers were found to be soluble in dimethylformamide (DMF) and poorly soluble or insoluble in water. In water and mixed DMF/H 2 O solvents, the copolymers were dispersed in micellar form by controlled addition of water to DMF solutions of copolymers under continuous intensive stirring. The micellar solutions in water were prepared by dialysis of solutions in DMF/H 2 O (95 vol% of H 2 O) against water. Solution properties of diblock copolymers of poly(HPMA) and poly(BA) were studied using static and dynamic laser light scattering to characterize the behavior of the copolymers at the supramolecular level. The effects of preparation mode, organic solvent (DMF) and copolymer chemical composition on the formation of micelles were studied. While a slower mixing procedure was optimal for copolymers with short poly(HPMA) blocks, a faster mixing was more suitable for copolymers having longer poly(HPMA) blocks. Finally, the dimensions of micelles in water were evaluated. The most compact micelles were prepared from copolymers having short hydrophilic poly(HPMA) blocks. On the other hand, the copolymer with the longest poly(HPMA) block formed micelles with the smallest size and the lowest density.

A time-resolved small-angle light scattering apparatus equipped with azimuthal integration by means of a conical lens or software analysis of scattering patterns detected with a CCD camera was developed. Averaging allows a significant reduction of the signal-to-noise ratio of scattered light and makes this technique suitable for investigation of phase separation kinetics. Examples of applications to time evolution of phase separation in concentrated statistical copolymer solutions and dissolution of phase-separated domains in polymer blends are given.

The temperature dependence of dynamic properties of solutions of a triblock copolymer with polystyrene outer blocks and a middle block of fully hydrogenated polybutadiene (M w =7.0×10 4 g mol −1 , mass fraction of PS 0.28) was studied in a selective solvent for the middle block, n-heptane. In dilute solutions, a gradual decomposition of the flower-like micelles was observed on heating. A more complex behavior was observed in semidilute solutions of the copolymer where three dynamic processes can be reliably extracted from the correlation functions. The fast mode corresponds to the collective diffusion mode of physically interconnected micelles, the broad middle mode is probably due to the tracer diffusion of polydispersed clusters (animal-like structures) formed by random association of the triblock copolymer and the slow mode is probably related to the diffusion of aggregates of insoluble polystyrene impurities. The crossover from relaxational to diffusive behavior was found for samples with c>5.5% ( w / v ). The scattered light intensity measurements revealed a phase transition for the solution with the concentration 4% (w/v) at a temperature of 79±2°C, which was related to the phase separation of polystyrene homopolymer present in a small amount in the copolymer used.

The concentration dependence of the self-diffusivity of a hydrogenated polystyrene-block-polybutadiene-block-polystyrene triblock copolymer in an n-heptane solution (c = 0.58−6.9 g/100 mL) was investigated using the pulsed field gradient NMR at 20−35 °C. The solvent is a preferential solvent for the middle block. At low concentrations, micelle-like aggregates (flowers) are observed. With increasing concentration larger aggregates (animals) are formed. These aggregates show a tendency to anomalous diffusion: exchange of micelles between the aggregated and the nonaggregated state as well as restricted diffusion. At the highest concentrations, individual diffusion of insoluble domains (nodes) is observed, but no transient network behavior. The width of the distribution of self-diffusivities corroborates the findings. Our results are in agreement with light scattering results published previously.

The self-diffusion of a polystyrene-b-poly(ethylene-co-propylene) diblock copolymer dissolved in a preferential solvent for the aliphatic block, n-decane, was investigated by pulsed field gradient NMR. The diblock copolymer forms micelles in solution, the structure of the solid polymer being preserved in the native solution because the polystyrene is in the glassy state. The equilibrium state is attained upon heating which again freezes in upon cooling to room temperature. The hydrodynamic radius of the micelles decreases by about 50% during this heating–cooling process. The concentration dependence of the self-diffusivity shows typical colloidlike behaviour, and it can be described by a Vogel–Fulcher–Tammann-like equation. No indications of crystallization at higher concentrations are observed in the micellar solution because the micellar sizes are slightly polydisperse. The self-diffusivity was measured up to the glasslike state, where in-cage- diffusion and dynamic heterogeneities could be detected.

This study investigated the effects of the speed of component mixing, total concentration of polymers and ionic strength of solvents on formation of interpolyelectrolyte complexes (IPECs) of calf thymus DNA with diblock copolymers of N-(2-hydroxypropyl)methacrylamide (HPMA) and 2-(trimethylammonio)ethyl methacrylate (TMAEMCl). The diblock copolymer consisting of a poly(HPMA) block (A) and poly(TMAEMCl) polycation block (B) with pendant quaternary ammonium groups and with molecular weight of A block higher than that of B was used in the study. Poly(TMAEMCl) polycation were used for comparison. Static and dynamic light scattering methods were used for characterisation of complexes. The apparent mass-average molecular weights, Mwa, and hydrodynamic radii, RHa, of slightly overcompensated IPECs (ϕ=[cation units]/[DNA negative charges]=1.1) prepared by fast mixing of components were found to be only slightly smaller than those prepared by slow mixing. Both Mwa and RHa of IPECs prepared under stoichiometric conditions (ϕ=1) decreased with decreasing total polymer concentration, cT, approaching Mw and RH of single DNA complexes which are the most suitable ones for DNA uptake into cells. The presence of NaCl in solutions resulted in a significant increase in Mwa and RHa of IPECS.

Photoinduced random association of HPMA copolymers containing photochromic spirobenzopyran (SBP) moieties in side-chain termini have been studied by static and dynamic light-scattering and spectroscopic methods. Experimental results gave evidence of photoinduced association in solvents with different polarity (water, dioxane). The driving force of this association is electrostatic dipole–dipole interactions between zwitterionic merocyanine forms of SBP molecules formed upon UV irradiation. The intermolecular association is only possible in solvents with a low thermodynamic quality for the copolymer close to its solubility limit. An increase in solvent quality or screening by co-ions suppresses the photoassociation. The kinetics of cluster formation and dissolution were also investigated by monitoring time dependences of the intensity of scattered light, hydrodynamic size and merocyanine absorbance. A common feature of all association processes is the initial growth of cluster sizes at short irradiation times followed by a plateau after the photostationary state of SBP moieties is achieved. In contrast to hydrodynamic diameter, the static light-scattering intensity increases monotonously, reflecting increasing mass and/or concentration of clusters. The dissolution was very slow in aqueous solutions. Both the formation and dissolution of clusters are faster in dioxane solutions. The kinetics of cluster dissolution was found to be twice as slow as the relaxation time of the spontaneous photochromic conversion of SBP moieties. © 1998 John Wiley & Sons, Ltd.

The self-assembly of calf thymus DNA with diblock copolymers of poly(N-(2-hydroxypropyl)methacrylamide) (HPMA) and polycations (PC) with amino or quaternary ammonium groups in their side chains was tested by static and dynamic light scattering methods in aqueous 0.15 M NaCl. We have observed formation of well defined clusters of single DNA interpolyelectrolyte complexes with hydrodynamic radii of about 300 nm. Long-term size stability of clusters has been found to be a function of chemical structure of PC and of diblock copolymer composition. The most stable clusters were obtained by DNA association with diblock copolymers consisting of a poly(HPMA) block (A) and polycation block (B) with quaternary ammonium groups in their side chains, with molecular weight of A block higher than that of B. In the opposite case, lower molecular weight of A block, slow aggregation of SIPEC clusters was observed. The micelle-like structure was proposed for these clusters.

The solution properties of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers containing various numbers of meso-chlorin e6 monoethylenediamine (Mce6) molecules attached to the copolymer via eithe...

The association of styrene−methyl methacrylate statistical copolymers in the selective solvent acetone (a thermodynamically good solvent for poly(methyl methacrylate and bad for polystyrene) was examined by static and dynamic light scattering methods. In dilute solutions, the dynamics was dominated by a single fast mode, whereas in semidilute solutions two modes were generally seen, with fast and slow mean relaxation times. The fast dynamic mode was related to the cooperative diffusion mode. The slow mode was associated with dynamics of polymeric clusters formed by the random association process. Experimental results were interpreted in terms of the coupling model of partly penetrating polydispersed clusters formed by random association of copolymers.

Dynamic properties of styrene-methyl methacrylate (MMA) statistical copolymer solutions in benzene, a solvent isorefractive with MMA, were studied by dynamic light-scattering spectroscopy (DLS) and by pulsed-field-gradient NMR (PFG-NMR). Two separate dynamic processes were found from the DLS results in the semidilute region. The fast process was related to the cooperation diffusion mode. The slow diffusive process was attributed to the dynamics of composition fluctuations. The diffusion coefficient of the slow process has the magnitude similar to the self-diffusion coefficient determined by PFG-NMR. Dynamic property of the slow polydispersity mode were qualitatively interpreted in terms of the theory developed for diblock copolymers.

Dissolution of polystyrene-block-poly(ethylene-co-propylene) (PS—PEP) in decane, a selective solvent for the PEP block, and dioxane, a selective solvent for the PS block, at room temperature leads to formation of metastable micellar structures, which convert into stable micelles with molar mass reduced several times after heating above ∼50°C. By comparing small-angle X-ray scattering (SAXS) and light scattering (LS) data, the following models of micellar structures are suggested: At room temperature, dissolution of PS— PEP in decane yields aggregates of micelles. These are detected by LS, while SAXS reflects the molar mass of individual micellar cores formed by PS blocks. At elevated temperature, these compound particles disaggregate and then reorganize into equilibrium micelles of reduced molar mass. Solutions of PS—PEP in dioxane at room temperature have a different character. The molar masses of the observed particles determined by SAXS are in a good agreement with LS results, so we can exclude aggregation of micelles in this solvent. Nevertheless, also here, after heat treatment, both SAXS and LS yield a molar mass that is about 5 times lower than that determined for unheated solutions. Metastable structures surviving from the solid-state morphology after dissolution in a selective solvent at room temperature may convert to classical equilibrium micelles only after heating.

Synchrotron-based time-resolved small-angle X-ray scattering was used to measure the early-stage spinodal decomposition kinetics in a highly viscous semidilute solution of polystyrene in dioctyl phthalate. Although strong nonlinearities in the kinetics were observed, a linear theory analysis could fit the evolution of the structure factor at short times and low wavenumbers. Nonlinearities become significant earlier at higher wavenumbers, which is consistent with recent computer simulation studies. From the linear theory analysis, the exponential relaxation rate of the structure factor R(q) was found to be linear in q 2 in the low-wavenumber region of the experiments, in agreement with mean-field theory for spinodal decomposition in polymer solutions. The wavenumber-dependent Onsager transport coefficient A(q), which is the Fourier transform of the nonlocal mobility in a polymer system, was determined to scale as q -4 . This q dependence, which is stronger than that predicted by existing theory, may be related to entanglement effects.

We examine the influence of the diverging concentration fluctuations near a spinodal on the dynamics of branched polymer solutions in the vicinity of a sol−gel transition. Dynamic light scattering ...

Solution properties of the statistical copolymers of alkyl methacrylates (AMA) with α-methyl-ω-hydroxy-poly(oxyethylene) methacrylates (MPOEMA) (nonionic polysoaps) were studied using static and dynamic ligh scattering as a function of monomer composition and concentration in aqueous and methyl cellosolve solutions. The solubility of the copolymers in water was found to be dependent on molar contant of AMA. While copolymers with low content of hexyl methacrylate (HMA) (0 and 20 mole %) were directly soluble in water, forming true solutions with a low content of large swollen aggregates, copolymers with a higher content of HMA or lauryl methacrylate (LMA) were not directly dispersable in water. A special procedure, the stepwise dialysis from methyl cellosolve solutions against water, had to be used to prepare them in the pseudomicellar form. The copolymers were directly soluble in methyl cellosolve and its water solution containing up to 60 vol.% of water. Nevertheless, the light scattering experiments were dominated by light scattering of swollen particles of aggregated copolymer molecules. The copolymers were not soluble in the mixtures containing 70-100 vol.% of water. Paramaters of aggregates in the mixture with 60 vol.% of water and in pure water were found to be very similar.

The association in aqueous solution and adsorption on polystyrene microspheres of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers containing photochromic azobenzene side chains were studied by light scattering and spectroscopic methods, respectively. Copolymers with a content of azobenzene in side chains, xa, 7 mol% were soluble in water only in the form of aggregates (pseudo-micelles) prepared by a slow increase in copolymer concentration. The adsorption plateau was greater for copolymers with xa 7 mol%. Moreover, the adsorption plateau for molecularly dissolved copolymer (xa 7 mol%). UV irradiation of HPMA copolymer influenced the self-association and adsorption properties due to cis-trans configuration changes of the azobenzene units in the side chains. It was found that aggregates have partially dissociated in response to UV irradiation. UV irradiation also has increased the copolymer adsorption. The effect has been small for molecularly dissolved copolymers (xa 7 mol%). Thus, irradiation induced a 60% increase in the adsorption for copolymers with xa = 11.5 and 12.5 mol% of azobenzene moieties. The changes of the copolymer adsorption upon irradiation have been related to changes in the inter- and intramolecular association and to conformation changes of adsorbed chains.

Branched polymers were prepared from the bifunctional 4,4'-diglycidyloxy-2,2-diphenylpropane (diglycidyl ether of bisphenol A) and hexafunctional poly(oxypropylene) diamine (Jeffamine T-403) at different distances from the gel point in the absence and presence of a diluent. Polymers with different amounts of intramolecular cycles were prepared by dilution during polymerization of the epoxide system with diglyme/butanol mixed solvent. The static and dynamic light scattering from dilute solutions of these epoxide samples was measured. The results are discussed in terms of existing gelation theories. The critical exponents of Mw lie between the values predicted by the Flory-Stockmayer and percolation theories and are shifted towards the percolation value with increasing fraction of intramolecular cycles. Polymer growth near the gelation threshold is discussed.

Polystyrene-block-poly(ethylene-co-propylene) solutions in decane have been investigated by dynamic and static light scattering. The dissolution of the diblock copolymer in a solvent, which is selective of aliphatic blocks, yields well-defined metastable micellar structures. These structures are converted into equilibrium micelles on heating and change into frozen micelles when cooled. A similar pattern is observed also in dioxane, which is a selective solvent for polystyrene blocks.

The solubility and association of water-soluble copolymers of N -(2-hydroxypropyl)methacrylamide (HPMA) containing both p -nitroaniline-terminated oligopeptide side-chains and N -2-hydroxyethylpiperazine- N ′-ethanesulfonic acid (HEPES) side-chains in aqueous solvents were investigated using light scattering methods. The weight-average molar masses, second virial coefficients, diffusion coefficients and hydrodynamic sizes of the copolymer molecules and their aggregates were studied as a function of the copolymer concentration, temperature and solvent pH. The copolymers with a low content ( p -nitroaniline were soluble molecularly in aqueous solutions. The water solubility was substantially enhanced by the presence of HEPES side-chains. The copolymers with a high content (∼7 mol%) of p -nitroaniline-containing side-chains associated in water, generally forming two types of micelles of different sizes. Micelle formation depended on hydrophobic and amphiphilic side-chain content, polymer concentration, temperature and solvent pH. Thus, macromolecules containing a higher amount of p -nitroaniline and a small amount of HEPES side-chains tended to form small, compact micelles with the hydrophobic p -nitroaniline molecules oriented into the core, while macromolecules with a high content of HEPES side-chains tended to form large micelles. The formation of large micelles was strongly dependent on solvent pH, due to the electrolyte behaviour of the HEPES moieties. The solution properties of the copolymers generally reflected the competition between these two association processes.