Tuning the Formation and Degradation of Layer-by-Layer Assembled Polymer Hydrogel Microcapsules

Abstract

Engineered polymer capsules are finding widespread importance in the delivery of encapsulated toxic or fragile drugs. The effectiveness of polymer capsules as therapeutic delivery vehicles is often dependent on the degradation behavior of the capsules because it is often necessary to release the encapsulated drugs at specific times and in certain locations. Herein we investigate the parameters that govern the formation and degradation of a recently introduced new class of polymer hydrogel capsules based on disulfide cross-linked poly(methacrylic acid). We report a new and efficient method for the synthesis of thiol-functionalized poly(methacrylic acid) (PMA(SH)), the main component of the capsules. Polymeric capsules were synthesized by the layer-by-layer deposition of PMA(SH) and poly(vinylpyrrolidone) (PVPON) on silica particle templates, followed by cross-linking the PMA(SH) layers and removing PVPON and the template particles. The disulfide cross-links provided a redox-active trigger for degradation that was initiated by a cellular concentration of glutathione. We demonstrate that increasing the degree of PMA(SH) thiol modification affords direct control over the thickness of the polymer film and the degradation rate of the polymer capsules. Furthermore, the degradation rate of the PMA(SH) capsules was independent of film thickness, suggesting a bulk erosion process.

Capsosomes with Multilayered Subcompartments: Assembly and Loading with Hydrophobic Cargo

“…This assembly was capped with a layer of PMA c , and the membrane of the carrier capsule consisting of poly(N-vinyl pyrrolidone) (PVP) and thiol-modified poly-(methacrylic acid) (PMA SH ) was built up via hydrogen bonding (Scheme 1). These two polymers were chosen as building blocks for the carrier capsule because disulfide-stabilized PMA capsules [29][30][31] are nontoxic, [32] (bio)degradable [33] and have been successfully applied to encapsulate genes, [8,34] peptides, [31] a monolayer of intact enzyme-loaded liposomes, [20,35] and drug-loaded oil droplets. [12] When the thiols in the polymer film are cross-linked and the silica template is removed, capsosomes containing multiple layers of liposomes are obtained.…”

The essential materials paradigms for regenerative medicine

“…These include features of pore architecture, including pore size, 24 shape, 25 and distribution, 26 elasticity, including moduli 27 and time-dependent deformation, 28 the surface energetics parameters such as hydrophobic-hydrophilic balance and molecular mobility. 29 In addition, the chemical functionality, 30 environmental responsiveness with respect to pH, 31 stress 32 and temperature, 33 the surface topography at micro-and nano-scale, 34 and biodegradation mechanisms such as hydrolysis and enzymatic degradation 35 and the rates of degradation 36 and metabolism of degradation products 37 will all play a role. Biological functionalization may be imparted by, for example, growth factors (e.g., nerve growth factor, 38 proteins such as laminin, 39 peptide motifs, 40 cellular antigens (CD molecules), genes/transcription factors or oxygen generating species).…”

Synthesis, characterization, and in vitro biocompatibility study of novel disulfide cross‐linked hydrogels based on poly(amic acid)

“…They can swell or completely dissolve once the disulfide bonds are cleaved by reducing reagents such as dithiothreitol (DTT), N-acetyl-cysteine, or glutathione. [16][17][18] In the previous study, we have performed preliminary research on the degradation of the disulfide bonds and PEG cross-linked PAA hydrogels. 19 In this research, the structure of PAA and hydrogels are characterized in detail.…”