The synthesis and study of polyphosphazenes for potential biomedical applications

This thesis describes the synthesis and investigation of novel polyphosphazenes for potential applications in the field of biomedicine. Specifically, this research focuses on the synthesis of (1) biodegradable polyphosphazenes bearing imidazolyl or ethyl glycinato side groups, (2) stable, pH-sensitive polyphosphazene hydrogels with methoxyethoxyethoxy and oxybenzoate side chains, and (3) polyphosphazenes bearing tyrosine-based side units.; A series of ethyl glycinato- and imidazolyl-substituted polyphosphazenes with p-methylphenoxy as a cosubstituent was synthesized to obtain biodegradable polymers with varying ratios of the side groups. The degradation products of these polymers are relatively nontoxic and would include glycine, ethanol, imidazole, phosphates and ammonia. The rate of degradation can be controlled by modifying the ethyl glycinato or imidazolyl content of the polymers. These polymers were investigated as potential substrates for skeletal tissue regeneration. The polymers were found to support the growth and proliferation of osteoblast-like cells comparable to or better than 50:50 poly(lactide-co-glycolide). The polyphosphazenes were also studied as matrices for the delivery of a small molecule drug (colchicine) and a macromolecular model (inulin).; The synthesis and characterization of pH-sensitive polyphosphazene hydrogels are described. A series of polyphosphazenes bearing methoxyethoxyethoxy and oxybenzoate side groups in varying ratios was synthesized. The oxybenzoate group was introduced to impart pH-sensitive behavior to the polymer. The alkylether unit was used to provide sites for radiation cross-linking and for enhanced water solubility. The cross-linked polymers swelled in aqueous media to yield hydrogels that exhibited pH-dependent swelling behavior. The release of a dye, Biebrich Scarlet, from the hydrogels was examined as model for the controlled release of bioactive agents.; Polyphosphazenes bearing tyrosine-based side groups have been synthesized. The tyrosine derivatives were linked to the phosphazene backbone either through tyrosine's amino group or the oxygen atom attached to its phenyl ring. A trimer model with tyrosine attached via the oxygen atom exhibited a pH-dependent solubility behavior consistent with the presence of a Zwitterionic species. At the polymer level, such pH-sensitive behavior was not observed due to the high water solubility of the alkylether cosubstituent. In the presence of Ca{dollar}sp{lcub}2+{rcub}{dollar}, the polymer formed a hydrogel. These polymers have potential applications in microencapsulation and drug delivery.