Biodegradable polymeric microspheres with "open/closed" pores for sustained release of human growth hormone

Abstract

A new approach for attaining Sustained release of protein is introduced, involving a pore-closing process of preformed porous PLGA microspheres. Highly porous biodegradable poly(D,L-lactic-co-glycolic acid) (PLGA) microspheres were fabricated by a single water-in-oil emulsion solvent evaporation technique using Pluronic F127 as an extractable porogen. Recombinant human growth hormone (rhGH) was incorporated into porous microspheres by a simple solution dipping method. For their controlled release, porous microspheres containing hGH were treated with water-miscible solvents in aqueous phase for production of pore-closed microspheres. These microspheres showed Sustained release patterns over an extended period; however, the drug loading efficiency was extremely low. To overcome the drug loading problem, the pore-closing process was performed in an ethanol vapor phase using a fluidized bed reactor. The resultant pore-closed microspheres exhibited high protein loading amount as well as sustained rhGH release profiles. Also, the released rhGH exhibited structural integrity after the treatment. (c) 2006 Elsevier B.V. All rights reserved.