Tuning the properties of pH-responsive and redox sensitive hollow particles and gels using copolymer composition

Abstract

Biodegradable pH-responsive hollow polymer particles offer excellent potential for preparing high performance biomaterials. Unfortunately, the established methods for pH-responsive hollow particle preparation are laborious and difficult to scale up. Recently, we reported that pH-responsive hollow particles could be prepared using solvent evaporation [Bird et al., Chem. Commun., 2011, 47, 1443. Here, we greatly expand and extend that work by investigating four new pH-responsive hollow particle systems based on poly(MMA-co-MAA) (methyl methacrylate and methacrylic acid) and poly(EA-co-MAA) (EA is ethyl acrylate). The hollow polymer particles were crosslinked with cystamine after preparation to give redox sensitive, biodegradable, hollow particles. For one of the systems a remarkable particle-in-hollow particle morphology was observed. The pH-triggered swelling of the hollow particles was studied and pH-triggered release of a model solute from these new hollow particles was demonstrated. The dispersions formed physical gels in the physiological pH range. The hollow particle physical gels had elastic modulus values as high as 4000 Pa at low total polymer concentrations. The swelling properties of the particles and the mechanical properties of the gels were tuneable using copolymer composition. The particles and gels could be disassembled with glutathione. The properties of these new gel-forming dispersions imply they have good potential for future application as injectable gels for regenerative medicine.

Injectable Biocompatible and Biodegradable pH-Responsive Hollow Particle Gels Containing Poly(acrylic acid): The Effect of Copolymer Composition on Gel Properties

“…Compared to the corresponding MAA-containing crosslinked particles, 31,32,34 Q max values for the PMMA-AA/CYS and PMMA-AA/DTP particles are lower. This is unexpected in terms of the higher hydrophilicity of AA relative to MAA.…”

“…At pH 6.0, large particles with D h from 2725 to 4789 nm were observed which increased from 5337 to 5560 nm as the pH was increased to 7.0 (Table S1, Figure S6, Supporting Information). pH-Triggered particle swelling has also been reported in PMMA-MAA and PEA-MAA particles cross-linked with either CYS or DTP, 31,32,34 where the swelling process was attributed to electrostatic repulsion between negatively charged carboxylate groups in the polymers which are effectively held together by their cross-links. 56,57 As the pH increases, the disulfide groups, which are present in CYS and DTP, undergo hydroxide ion-mediated cleavage.…”

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

“…Preparation and characterisation of PMMA-MAA and PEA-MAA non-crosslinked particles Dispersions of PMMA-29MAA-, PMMA-38MAA-, PMMA-65MAA-, PEA-30MAA-and PEA-65MAA-based non-crosslinked particles were prepared by the sequential emulsication-solvent evaporation protocol described previously (Scheme 1a). 21 An important discovery in this work was that the rate of addition of the copolymer solution greatly affected the dispersion stability. In this study an optimized addition rate of the CH 2 Cl 2 -MeOH/ copolymer solution was established (10 ml min À1 ), which was much lower than that employed previously 53 and resulted in the formation of homogeneous, colloidally stable particle dispersions ( Fig.…”

“…The polydispersity of the samples was due to the turbulent shear ow during the high shear mixing. 21,39 If required, the polydispersity could be reduced by fractionation.…”

Shear Induced Morphological Transformation of Large Compound Micelles Formed by Glutathione End‐capped Poly(4‐vinylpyridine)

“…[5][6][7][8][9] Among the assemblies, those that are responsive to environmental stimuli are especially interesting since they can be used as smart carrier for controlled drug release, chemical and biological sensors and so on. [10][11][12][13][14][15] Usually, the smart assemblies are responsive to pH, temperature, light, magnetic field and so on. Compared to those conventional smart assemblies, shear-responsive ones are newly emerged [16] and have attracted more and more attention as they could be used as carriers for drug delivery in biological systems and other circumstances where shear force exists.…”