Processing of biodegradable polymers in supercritical carbon dioxide

The biodegradable polymer poly(lactide-co-glycolide) (PLGA) was processed with the nontoxic solvent, supercritical carbon dioxide (SC-CO₂). Novel processing techniques were developed to produce high purity PLGA biomaterials for use in biomedical applications. Microporous PLGA matrices designed for tissue engineering applications were produced by rapid depressurization of the polymer saturated with SC-CO₂. Protein was encapsulated within the porous matrices, including basic fibroblast growth factor, bFGF, an angiogenic growth factor known to promote new blood vessel growth in vivo. The biological activity of bFGF encapsulated within the porous PLGA matrices and released from the polymer upon exposure to an aqueous buffer was measured in vitro. Up to 60 percent of the encapsulated bFGF was released from PLGA in an active state. Treatment in SC-CO₂ did not have an adverse affect on the biological activity, as the percentage of recovered bFGF was comparable to alternative techniques. In addition, PLGA was synthesized by solution polymerization in SC-CO₂. Copolymers of lactide and glycolide were synthesized with weight-averaged molecular weights up to 30,000 and polydispersities of 2.3. The randomness of the copolymer chain was determined by calculating the average block lengths of glycolide and lactide. The molecular weight, polydispersity, and average block lengths of lactide and glycolide of PLGA synthesized in SC-CO₂ were comparable to biodegradable polymers made via bulk polymerization. Furthermore, PLGA synthesized in SC-CO₂ was purified by extracting unreacted monomer from the polymer phase. Biodegradable polymer processing in SC-CO₂ is proposed as a novel technique for producing high purity polymer for biomaterial applications.