Study of poly(methacrylic acid) hydrogel capsules: structural properties and biomedical applications

© 2010 Dr. Siow-Feng ChongNanoengineered hydrogel capsules (HCs) fabricated from the layer-by-layer (LbL) technique have emerged as versatile multifunctional carrier systems. For successful biomedical applications, basic requirements such as controlled encapsulation and cargo release have to be fulfilled. Additionally, this includes control over capsule properties such as composition, stability, permeability, functionality and degradability. This thesis focuses on the study of polymer HCs obtained from the LbL technique by the sequential deposition of poly(methacrylic acid) (PMA) and poly(vinyl pyrrolidone) (PVPON) to form hydrogen-bonded multilayered films that disassemble above pH 7. To prevent disassembly, the multilayer was stabilized with disulfide linkages. Polymeric carriers crosslinked with disulfide linkages can be degraded in a reducing environment, such as that found in the cytosol, resulting in selective release of cargo upon internalization of HCs by cells. In particular, the suitability of PMA HCs for drug delivery applications are described, from encapsulation to delivery of vaccines to professional antigen presenting cells (APCs). The encapsulation procedures provide control over the loading of cargo within stable and degradable carriers. To enhance the feasibility of PMA HCs as potential carriers for fragile biomolecules, thiol–disulfide exchange was employed in replacement of the oxidation-stabilized HCs. With the developed approach, the encapsulation efficiency of PMA HCs was improved, allowing confinement of smaller, non-charged cargo. To assess the feasibility of PMA HCs for in vivo applications, the effect of surface functionality was investigated. This study included immobilizing poly(ethylene glycol) (PEG) onto the carrier and demonstration of decreased protein adsorption from the PEG-immobilized carrier. The presented studies have significantly contributed to the establishment of LbL capsules and, in particular, PMA HCs, as potential carrier vessels for diverse biomedical applications such as drug delivery vehicles, microreactors and artificial cells