Abstract

Purpose: The purpose of our present study was to investigate the feasibility of prolonged delivery of a small synthetic peptide, MEP421, with a biodegradable PLGA microsphere depot formulation. Methods: MEP421 loaded PLGA microspheres were prepared by the conventional W₁/O/W₂ double emulsion-solvent evaporation method and the in vitro and in vivo drug release profiles from PLGA microspheres were investigated. Results: MEP421 loaded PLGA microspheres with a suitable particle size (mean diameter about 20–35 μm based on the preparation conditions) and high entrapment efficiency (>90%) were prepared. The in vitro release study showed sustained drug release over 30 d with obvious “burst release” in the first 24 h. Such “burst release” could be decreased by introducing high viscosity grade PLGA into the microsphere matrix. The results of our present studies also showed a good correlation (r=0.9746) between in vitro and in vivo drug release. Conclusions: MEP421 PLGA microspheres can be uniformly suspended in aqueous medium for subcutaneous injection, and may be used for sustained chronic delivery of MEP421 to Alzheimer’s patients.


Keywords:  PLGA   Microspheres   MEP421   Sustained release   Double emulsion-solvent evaporation