Evaluation of synthetically and naturally derived polymers for drug delivery and adhesion reduction applications

Abstract

Polymeric materials have a wide application of use in biomedical applications. The evaluations of several polymers (synthetically and naturally derived) are presented in this dissertation as drug/protein delivery vehicles and solid adhesion barriers. A blended polymer matrix consisting of poly(ethylene glycol)-grafted-chitosan (PEG-g-CHN) and poly(lactic-co-glycolic acid) (PLGA) was used to produce microspheres for therapeutic protein delivery. The release kinetics of a model protein was also investigated as PEG-g-CHN content was varied. A hamster cheek pouch microvascular model was utilized to evaluate the inflammatory potential of both the PEG-g-CHN/PLGA microspheres and released basic fibroblast growth factor (bFGF). We found the protein release rate is regulated by PEG-g-CHN content, and the bFGF released from the microspheres did not produce an inflammatory response in the hamster cheek pouch blood vessels. Next, in order to reduce post surgical abdominal adhesions in rats, we evaluated the efficacy of two different barrier materials: crosslinked hyaluronan (HA) films and oxidized dextran/N-carboxyethyl chitosan (Odex/CEC) hydrogel. Use of either barrier resulted in significantly lower adhesion severity scores than untreated animals. Finally, microgels composed of Odex/CEC were synthesized to deliver anti-inflammatory drugs (guanidinoethyl disulfide) with the goal of reducing nitric oxide production and oxidative damage following injury. The microgels were characterized after synthesis by measuring the release kinetics of drug and effective diameter. The inflammatory potential of the microgels were evaluated using both a macrophage cell culture model and a murine subdermal implantation model. The drug release kinetics experiments demonstrated a burst release of drug within 24 hours in vitro and moderate drug release up to 9 days. The microgels with and without encapsulated drug produced a mild inflammatory response in vitro when the particles were co-incubated with macrophage cells. The results of the subdermal implantation study suggested that the drug attracted more inflammatory cells into the implant site compared with the microgel vehicle alone, but produced less capsule fibrosis with the high dose of drug. Overall, the results presented in this dissertation indicate that the polymers studied were promising materials for use as drug/protein delivery vehicles and adhesion barriers.