| Biodegradable polyanhydrides are of interest as drug delivery devices due to their biocompatibility and excellent controlled release features. Therapeutic agents can be physically or chemically incorporated into a polymer. In this thesis, drug incorporation into a polymer occurs by either chemical insertion into the backbone or attachment as a pendant group.; A series of poly(anhydride-esters) that biodegrade into salicylic acid were synthesized where the molecule connecting the salicylic acid moieties (i.e., "linker") was modified to manipulate the polymer physical properties and degradation profiles. Polymers of high molecular weight (Mw) were obtained with linear alkyl chain linkers, while polymers containing aromatic linkers yielded lower Mw materials. Significantly, polymers containing the highest aliphatic content degraded faster than the ones with aromatic/aliphatic branched linkers.; Similarly, other bioactive agents were chemically incorporated to obtain polymeric prodrugs. Antioxidative phenolic compounds (e.g., vanillic and syringic acids) were incorporated into poly(anhydride-ester) backbones (67-78 wt %) to yield drug delivery systems for rapid, controlled drug-release applications (e.g., topical therapies). These aromatic prodrugs underwent fast in vitro drug release (5-7 days) and exerted no significant toxicity towards L929 fibroblasts. The relationship between the methoxy substitution on the phenols, the linker structure, and the polymer physical properties was assessed with respect to drug release. Thus, the steric hindrance of the methoxy groups decreased the Mw and increased the glass transition temperature (Tg) and solubility.; Other therapeutic compounds such as beta-lactam antibiotics (ampicillin and amoxicillin) were chemically inserted (up to nearly 82% by weight) into a polymer backbone to obtain prodrugs that may prevent local infections associated with medical devices. Antibiotics were chosen based on their wide use for the prophylaxis and treatment of bacterial infections as well as their thermal sensitivity; for polymer incorporation, solution polymerization methods were used. Polymers displayed antimicrobial properties against Escherichia coli and Staphylococcus aureus.; Lastly, a new synthetic methodology was developed to incorporate monofunctional phenolic antiseptics into a polymeric backbone as pendant group that expands the range of drugs that can be potentially incorporated while obtaining materials that may be useful as antiseptic coatings or topical disinfectants to prevent and control infection. |
