Curcumin delivery from poly(acrylic acid-co-methyl methacrylate) hollow microparticles prevents dopamine-induced toxicity in rat brain synaptosomes.

The potential of poly(methyl methacrylate-co-acrylic acid) (PMMA-AA) copolymers to form hollow particles and their further formulation as curcumin delivery system have been explored. The particles were functionalized by crosslinking the acrylic acid groups via bis-amide formation with either cystamine (CYS) or 3,3'-dithiodipropionic acid dihydrazide (DTP) which simultaneously incorporated reversibility due to the presence of disulfide bonds within the crosslinker. Optical micrographs showed the formation of spherical hollow microparticles with a size ranging from 1 to 7 µm. Curcumin was loaded by incubation of its ethanol solution with aqueous dispersions of the cross-linked particles and subsequent evaporation of the ethanol. Higher loading was observed in the microparticles with higher content of hydrophobic PMMA units indicating its influence upon the loading of hydrophobic molecules such as curcumin. The in vitro release studies in a phosphate buffer showed no initial burst effect and sustained release of curcumin that correlated with the swelling of the particles under these conditions. The capacity of encapsulated and free curcumin to protect rat brain synaptosomes against dopamine-induced neurotoxicity was examined. The encapsulated curcumin showed greater protective effects in rat brain synaptosomes as measured by synaptosomal viability and increased intracellular levels of glutathione.

Injectable biocompatible and biodegradable pH-responsive hollow particle gels containing poly(acrylic acid): the effect of copolymer composition on gel properties.

The potential of various pH-responsive alkyl (meth)acrylate ester- and (meth)acrylic acid-based copolymers, including poly(methyl methacrylate-co-acrylic acid) (PMMA-AA) and poly(n-butyl acrylate-co-methacrylic acid) (PBA-MAA), to form pH-sensitive biocompatible and biodegradable hollow particle gel scaffolds for use in non-load-bearing soft tissue regeneration have been explored. The optimal copolymer design criteria for preparation of these materials have been established. Physical gels which are both pH- and redox-sensitive were formed only from PMMA-AA copolymers. MMA is the optimal hydrophobic monomer, whereas the use of various COOH-containing monomers, e.g., MAA and AA, will always induce a pH-triggered physical gelation. The PMMA-AA gels were prepared at physiological pH range from concentrated dispersions of swollen, hollow, polymer-based particles cross-linked with either cystamine (CYS) or 3,3'-dithiodipropionic acid dihydrazide (DTP). A linear relationship between particle swelling ratios, gel elasticity, and ductility was observed. The PMMA-AA gels with lower AA contents feature lower swelling ratios, mechanical strengths, and ductilities. Increasing the swelling ratio (e.g., through increasing AA content) decreased the intraparticle elasticity; however, intershell contact and gel elasticity were found to increase. The mechanical properties and performance of the gels were tuneable upon varying the copolymers' compositions and the structure of the cross-linker. Compared to PMMA-AA/CYS, the PMMA-AA/DTP gels were more elastic and ductile. The biodegradability and cytotoxicity of the new hollow particle gels were tested for the first time and related to their composition, mechanical properties, and morphology. The new PMMA-AA/CYS and PMMA-AA/DTP gels have shown good biocompatibility, biodegradability, strength, and interconnected porosity and therefore have good potential as a tissue repair agent.

pH-responsive physical gels from poly(meth)acrylic acid-containing crosslinked particles: the relationship between structure and mechanical properties.

Gels that feature high internal porosity and have both high elasticity and ductility have potential to provide immediate load support and enable subsequent tissue regeneration of damaged soft tissue if combined with cells. Herein, we report results from a recent investigation of novel poly(methyl methacrylate-co-methacrylic acid), (PMMA-MAA) and poly(ethyl acrylate-co-methacrylic acid), (PEA-MAA) biodegradable, pH-sensitive particle gels which are with high porosity, elasticity and ductility. These gels formed at physiological pH range and are potentially injectable. The particles were prepared using solvent evaporation. They were functionalized by crosslinking the MAA groups of the particles via bis-amide formation with either cystamine (CYS) or 3,3'-dithiodipropionic acid dihydrazide (DTP) which simultaneously incorporated reversibility due to the presence of disulphide bonds within the crosslinker. The crosslinked particles were observed by dynamic light scattering to swell appreciably in size upon increasing the pH. Concentrated dispersions formed elastic and ductile physical gels within the physiological pH range. A key finding of this study was that for crosslinked particles of similar composition the formation of considerably more elastic and ductile gels was observed from the most lightly crosslinked particles. Furthermore, compared to the PMMA-MAA/CYS and PEA-MAA/CYS gels, those formed from DTP-crosslinked particles had higher elasticity, thicker pore walls and improved interconnectivity. For the PMMA-MAA/DTP gels an elastic modulus value as high as 100 kPa and a yield strain greater than 100% were observed for a gel containing only 5 wt% of particles. The improved mechanical properties of these new gel-forming dispersions imply that they now have good potential for future application as injectable gels for regenerative medicine.

Effect of polymer molecular weight and solution pH on the surface properties of sodium dodecylsulfate-poly(ethyleneimine) mixtures.

The effect of polymer molecular weight and solution pH on the surface properties of the anionic surfactant sodium dodecylsulfate, SDS, and a range of small linear poly(ethyleneimine), PEI, polyelectrolytes of different molecular weights has been studied by surface tension, ST, and neutron reflectivity, NR, at the air-solution interface. The strong SDS-PEI interaction gives rise to a complex pattern of ST behavior which depends significantly on solution pH and PEI molecular weight. The ST data correlate broadly with the more direct determination of the surface adsorption and surface structure obtained using NR. At pH 3, 7, and 10, the strong SDS-PEI interaction results in a pronounced SDS adsorption at relatively low SDS and PEI concentrations, and is largely independent of pH and PEI molecular weight (for PEI molecular weights on the order of 320, 640, and 2000 Da). At pH 7 and 10, there are combinations of SDS and PEI concentrations for which surface multilayer structures form. For the PEI molecular weights of 320 and 640 Da, these surface multilayer structures are most well-developed at pH 10 and less so at pH 7. At the molecular weight of 2000 Da, they are poorly developed at both pH 7 and 10. This evolution in the surface structure with molecular weight is consistent with previous studies, (1) where for a molecular weight of 25,000 Da no multilayer structures were observed for the linear PEI. The results show the importance with increasing polymer molecular weight of the entropic contribution due to the polymer flexibility in control of the surface multilayer formation.

Effect of architecture on the formation of surface multilayer structures at the air-solution interface from mixtures of surfactant with small poly(ethyleneimine)s.

The impact of ethyleneimine architecture on the adsorption behavior of mixtures of small poly(ethyleneimines) and oligoethyleneimines (OEIs) with the anionic surfactant sodium dodecylsulfate (SDS) at the air-solution interface has been studied by surface tension (ST) and neutron reflectivity (NR). The strong surface interaction between OEI and SDS gives rise to complex surface tension behavior that has a pronounced pH dependence. The NR data provide more direct access to the surface structure and show that the patterns of ST behavior are correlated with substantial OEI/SDS adsorption and the spontaneous formation of surface multilayer structures. The regions of surface multilayer formation depend upon SDS and OEI concentrations, on the solution pH, and on the OEI architecture, linear or branched. For the linear OEIs (octaethyleneimine, linear poly(ethyleneimine) or LPEI(8), and decaethyleneimine, LPEI(10)) with SDS, surface multilayer formation occurs over a range of OEI and SDS concentrations at pH 7 and to a much lesser extent at pH 10, whereas at pH 3 only monolayer adsorption occurs. In contrast, for branched OEIs BPEI(8) and BPEI(10) surface multilayer formation occurs over a wide range of OEI and SDS concentrations at pH 3 and 7, and at pH 10, the adsorption is mainly in the form of a monolayer. The results provide important insight into how the OEI architecture and pH can be used to control and manipulate the nature of the OEI/surfactant adsorption.