Controlled release of recombinant insulin-like growth factor from a novel formulation of polylactide-co-glycolide microparticles

The purpose of the current study was to develop a controlled-release delive ry system for recombinant insulin-like growth factor (rhlGF-1). Polylactide -co-glycolide (PLG) microparticles with entrapped rhlGF-1 were prepared by a novel emulsion based solvent evaporation process. Microparticles with two loading levels of rhlGF-1 were prepared (4 and 20% w/w). The integrity of released rhlGF-1 was characterized by RP-HPLC, SDS-PAGE and a bioactivity a ssay. In vitro and in vivo release profiles of rhlGF-1 from these micropart icles were also evaluated. Reproducible batches of microparticles with 4% a nd 20% w/w loading of rhlGF-1 were prepared, with excellent encapsulation e fficiency (81 and 85% of total protein respectively entrapped). The protein retained integrity after the microencapsulation process as evaluated by RP -HPLC. SDS-PAGE and bioactivity assay. The in vitro profiles exhibited a si gnificant burst release of rhlGF-1 (20-30%), followed by controlled release of protein for up to 28 days. A similar level of burst release was observe d in vivo, followed by controlled release of protein for 14-18 days. In add ition, there was a surprisingly close correlation between in vitro and in v ivo release rates. PLG microparticles with entrapped rhlGF-1 are a promisin g delivery system which may allow rhlGF-1 to be used for a broad range of t herapeutic indications. (C) 2001 Elsevier Science B.V. All rights reserved.