POLYOXYETHYLENE-i-POLYOXYPROPYLENE-6-POLYOXYETHYLENE-g-POLY(ACRYUC ACID) POLYMERS (SMART HYDROGEL~(TM)) AS A CARRIER IN CONTROLLED DELIVERY OF PROTEINS AND PEPTIDES

摘要

The explosive development of protein and peptide drugs has ushered in a need for effective delivery systems for such drugs. Two decades of studies of protein delivery from polymeric systems have revealed the great poten-tial of gels that respond to environmental stimuli, such as temperature, pH, etc.1 The mechanism of the release is affected by polymer design. "Intelligent" amphiphilic copolymers emerge as a novel approach in the application of thermodynamically stable self-assembling lyophilic colloids to protein and peptide delivery. Here, we introduce the paradigm of ther-mally reversible gels (TRG) for protein and peptide delivery. We developed a polymeric solution that is a free-flowing liquid at ambient temperature and gels at body temperature. Such TRG system would be easy to admin-ister in topical applications. Moreover, loading of such system with pro-teins could be achieved by simple mixing with already prepared standard polymer formulation. When gelled, the system releases the drug in a con-trolled manner. Temperature-gelling PEO-PPO-PEO triblock copolymers of polyethylene oxide) (PEO) and polypropylene oxide) (PPO), known as -Pluronic? surfactants were copolymerized with poly(acrylic acid) (PAA). The resulting copolymer, (Smart Hydrogel?) is easily administered into a desired body site and possesses increased retention time due to its bioadhe-sive properties 2. Smart Hydrogel? can be applied as a carrier gel in pro-tein and peptide delivery, as outlined below.