| This research focused on the synthesis of new polyanhydride homopolymers for controlled drug delivery applications. The ideal polymer would provide drug release rates comparable or superior to those of known polyanhydrides. The polymer would also be more easily processed at lower temperatures. The major approach to the desired material involved the synthesis of new hydrophobic, aromatic diacid monomers containing branched, aliphatic spacers. Thus, 1,3-bis( p-carboxyphenoxy)-2,2-dimethylpropane, 1,2-bis(p-carboxyphenoxy)propane (1PO), 1,2- or 2,2-bis(p-carboxyphenoxy)dipropylether (2PO), and 1,2- or 2,2-bis[1- or 2-(p-carboxyphenoxy)propoxy]propane and 1-[2-(p-carboxyphenoxy)propoxy]-2-[1-(p-carboxyphenoxy)propoxy]propane and 2-[2-(p-carboxyphenoxy)propoxy]-1-[1-(p-carboxyphenoxy)propoxy]propane (3PO) were synthesized using Mitsunobu and aromatic nucleophilic substitution reactions. The monomers were prepolymerized using acetic anhydride and then melt polymerized to obtain the corresponding homopolymers. Poly[1,3-bis( p-carboxyphenoxy)-2,2-dimethylpropane anhydride] contained a symmetrical aliphatic linkage, which resulted in a high degree of crystallinity and a high melting point. The other polyanhydrides, which contained one to three 1,2-propylene oxide units, were amorphous with Tgs ranging from 27–111°C. The Tg decreased as the number of propylene oxide units increased. Both P(1PO) and P(2PO) had Tgs in the optimum range for controlled release applications. Thus, the polymerization conditions used to prepare the polymers were optimized to obtain the highest molecular weight products. The molecular weight and mass loss of polymer discs were monitored and used to determine the rates of hydrolysis and erosion. Drug release rates were determined by measuring the amount of methylene blue released from methylene blue-containing discs. The highly hydrophobic aromatic homopolymers displayed an erosion profile with long induction periods (3–10 weeks). During the induction period, the molecular weight decreased continuously. When the weight average molecular weight (MW) of P(1PO) reached approximately 9200 g/mol (a 43% decrease) the polymeric devices began to erode. When the MW of P(2PO) reached approximately 5700 g/mol (a 68% decrease), the devices began to erode. The release of methylene blue was not as controlled as the release of other agents from injection molded polyanhydride samples. This was attributed to the sub-optimum processing conditions that could not produce well consolidated samples. |
