The mechanism of PLA microparticle formation by water-in-oil-in-water solvent evaporation method

Microparticles containing ovalbumin as a model protein drug were prepared using poly(L-lactide; PLA) with a water-in-oil-in-water emulsion/solvent evaporation technique. The dispersed phase was PLA dissolved in dichloromethane (DCM), and the continuous phase was water-containing polyvinyl pyrolidone (PVP) as stabilizer with sodium chloride. Microparticle characteristics, loading efficiencies, protein distribution in microparticles, and in-vitro release properties were investigated. The OVA leaking into the continuous phase during the formation of microparticle by DCM evaporation was also evaluated. Results show that OVA was successfully entrapped in the microparticles with trapping efficiencies up to 72%, loading level 8.7% w/v, and particle size 14 microm. The semi-solid suspension changes to a solid particle happened during a 10-min period. Total protein-leaking amount was reduced after addition of NaCl in the continuous aqueous phase, which resulted from reducing the solidification time and protein-leaking rate. Using 5% w/v NaCl in the continuous phase resulted in higher loading content (87.2 +/- 1.0 microg/mg), and loading efficiency (72.2%), which resulted from more protein in the deeper layer (50.2 +/- 2.3 microg/mg) and higher microparticle yield (75.2%) than without NaCl (loading content: 74.0 +/- 1.0 microg/mg; loading efficiency 51.8%; deeper layer content: 18.3 +/- 3.5 microg/mg; yield: 63.6%). These results constitute a step forward in the improvement of existing technology in controlling protein encapsulation and delivery from microparticles prepared by the multiple emulsion solvent evaporation method.