Aliphatic polyesters with pendent unsaturation and poly(ethylene glycol) groups: Synthesis, characterization, and encapsulation studies
Aliphatic polyesters are widely used in biomaterial applications including drug delivery and tissue engineering because they are both biocompatible and biodegradable. However, these materials are primarily semi-crystalline, hydrophobic, solids at biologically relevant temperatures and lack functionality for altering their properties. Consequently methods to incorporate functional groups pendent to aliphatic polyesters and thereby tune their properties are sought. Pendent functionalization presents a significant challenge as the degradable nature of the polyester backbone severely limits the chemistry that can be performed without inducing degradation. The focus of this thesis is the preparation of pendent-functionalized aliphatic polyesters by controlled methods to give well-defined materials with a diverse range of functional moieties and physical properties.
Pendent functionalization was achieved through the synthesis of α-substituted lactone monomers, followed by Sn(II) mediated ring-opening polymerization and post-polymerization modifications. Lactone monomers substituted with allyl, cyclopentene, and acetylene groups were prepared and their homo-/copolymerization chemistry was studied. Post-polymerization modifications that could be achieved without degradation or cross-linking were explored to give polyesters with dramatically altered properties relative to conventional aliphatic polyesters. Water-soluble PEG-grafted polyesters, as well as, polyesters with pendent oligopeptide sequences and drug moieties were prepared. The suitability of these materials for biomaterial applications was evaluated by cytotoxicity testing using mouse fibroblasts and human red blood cells. The application of the pendent-functionalized polyesters as polymer-drug conjugates and cross-linked microparticles was also explored.