A Combined Micelle and Poly(Serinol Hexamethylene Urea)-Co-Poly(N-Isopropylacrylamide) Reverse Thermal Gel as an Injectable Ocular Drug Delivery System

We have developed an in situ-gelling polymer system comprised of drug-loaded micelles encapsulated within a reverse thermal gel (RTG) as an injectable ocular drug delivery system. The RTG chemistry employs a novel poly(N-isopropylacrylamide) (PNIPAAm) polymer--designed to permit complete physiological clearance of the system during degradation--coupled to a poly(serinol hexamethylene urea) (PSHU) backbone, which was designed to mimic natural materials. Inclusion of drug-loaded micelles significantly improved release kinetics of the poorly-soluble corticosteroid triamcinolone acetonide; the combined system is projected to sustain release for approximately one year based on in vitro testing. Both the RTG and micelles were well tolerated after intravitreal injection in rats.