Protein-loaded poly( dl-lactide-co-glycolide) microparticles for oral administration: formulation, structural and release characteristics

Abstract

FITC-labelled bovine serum albumin has been entrapped in sub-5 micron particles of poly( dl-lactide-co-glycolide copolymer) (PLG) using a water-in-oil-in-water (w/o/w) emulsification-solvent evaporation technique. The concentration of PVA stabiliser in the external continuous phase was found to affect not only the particle size, size distribution and protein content but also the release characteristics and internal structure of the microparticles. The importance of primary emulsification was underlined by the finding that the protein content of microparticles with mean size 1 μm could be increased from about 1% w/w to around 12% w/w by increasing the amount of protein added to the primary emulsion and the homogenisation time in this stage. Under conditions of low stabiliser concentration, multi-nucleate particles formed by polymer precipitation and envelopment of the droplets of the primary w/o emulsion. In this case surface protein loading was of the order of 30% w/w. Under conditions of high PVA stabiliser concentration, disruption of the primary emulsion occurred, resulting in sub-micron particles which were characterised by a high surface protein loading of the order of 70% w/w. A mechanism for protein microencapsulation is presented which is heavily influenced by the shear stresses induced during the process of secondary emulsification. This can explain certain aspects of the relationship between microparticle size and size distribution, protein content and release and the structural characteristics of microparticles produced using the w/o/w emulsification/solvent evaporation technique.