Novel composite microparticles for protein stabilization and delivery

The aim of this work was to develop a novel composite alginate/poly(lactic-co-glycolic) acid microparticulate system for protein stabilization and delivery using bovine insulin as model drug. Alginate particles, prepared by ionic gelation, were embedded into PLGA microparticles using the solvent diffusion evaporation technique. Actual loading was determined by micro-BCA protein assay for total insulin and by reversed phase-high performance liquid chromatography for soluble insulin. insulin loaded composite microparticles showed reproducible encapsulation efficiency with a higher soluble insulin content when compared to conventional microparticles. Bovine insulin in vitro release studies and adsorption behavior were investigated in 10 mM glycine buffer (pH 2.8) at 37 degrees C. The stability of bovine insulin, solubilized in the above mentioned buffer, was studied as well. In this case, bovine insulin showed to be instable at the investigated conditions and 55% of insulin was lost after 7 days. However, composite microparticle release, characterized by a low burst effect, lasted up to 4 months. Moreover, no significant peptide adsorption on blank PLGA or blank composite microparticles was observed while, a strong interaction between alginate particles and bovine insulin was detected. (c) 2008 Elsevier B.V. All rights reserved.