Description |
Thermoplastic biodegradable hydrogels based on star-shaped PEO-PLA and PEO-PCL block copolymers were synthesized and investigated as an injectable, biodegradable drug delivery system. The rationale of using the star-shaped polymers is based on their unique physical properties in solution and bulk state. Star-shaped polymers are known to display small hydrodynamic volume and low melt and solution viscosities, even at high molecular weights. Such behaviors are important for the drug delivery applications, because they affect the system formulation, drug release, and polymer degradation. Star-shaped block copolymers were synthesized by a divergent method, where star-shaped PEO was synthesized first by an anionic polymerization of ethylene oxide initiated with metallated plurifunctional initiators. The block copolymers were prepared by the ring-opening polymerization of L-lactide and e-caprolactone in the presence of star-shaped PEO and catalytic amount of stannous octoate. Equilibrium swelling, thermal behavior, and solution properties of the synthesized star-shaped polymers were examined. The block copolymers were swollen in distilled water, and the degree of swelling decreased as the number of arms increased. The melting point, crystallinity, and phase separation decreased with the degree of branching. Solution viscosity of the star-shaped PEO, which correlates with the hydrodynamic volume, decreased with degree of branching. Solution viscosity of star-shaped PEO-PLA and PEO-PCL block copolymers in methylene chloride was also found to decrease as the number of arms increased. Polypeptide-loaded microspheres were prepared from star-shaped PEO-PLA and PEO-PLA block copolymers, and the drug release profiles were investigated in vitro. It was observed that the physical properties due to molecular architecture influenced the microsphere preparation and drug release. As the number of arms increased, the drug release was found to increase in the latter phase. It was concluded that this distinct release profile was due to an accelerated degradation of the highly branched polymer. The results obtained in this study demonstrate the unique properties of star-shaped polymers and their feasibility for polypeptide delivery. In conclusion, drug delivery system fabrication, drug release profiles, and the in vivo fate of the drug carrier can be improved by using thermoplastic biodegradable hydrogels based on star-shaped polymers. |