Controlled release of protein drugs from newly developed amphiphilic polymer-based microparticles composed of nanoparticles.

A novel formulation of biodegradable microparticles was developed for the sustained release of peptide and protein drugs. The microparticles were formed by the aggregation of protein nanoparticles through water-in-oil (W/O) emulsion-lyophilization and subsequent solid-in-oil-in-water (S/O/W) emulsion-solvent evaporation. Amphiphilic copolymers were used as an emulsifier in the W/O emulsion and matrix of the microparticles. Among the various copolymers investigated, poly(lactide-co-glycolide)-grafted dextran (Dex-g-PLGA) was chosen as the best candidate on the basis of the encapsulation efficiency and in vitro release profile, the near zero-order release without a significant initial burst, of human growth hormone (hGH). The release rate of hGH was controllable by changing the composition of Dex-g-PLGA. The in vivo release studies using normal mice revealed that the plasma concentration of hGH was maintained for 1week without a significant initial burst. The enhancement of biological activity of hGH by sustained release was confirmed by measuring the IGF-1 concentration and body weight of hypophysectomized mice. These results suggest the high potential of the newly developed microparticles for the sustained release of biopharmaceuticals. Copyright 2009 Elsevier B.V. All rights reserved.