Influence of experimental parameters on the characteristics of poly(lactic acid) nanoparticles prepared by a double emulsion method.

Nanoparticles were prepared by the double emulsion method (w/o/w), using methylene chloride as an organic solvent and polyvinyl alcohol (PVA) or human serum albumin (HSA) as a surfactant. Experimental parameters such as the preparation temperature, the solvent evaporation methods, the internal aqueous phase volume, the surfactant concentration and the polymer molecular weight were investigated for particle size, the zeta potential, the residual surfactant percentage and the polydispersity index. Preparation parameters leading to particles with well-defined characteristics such as an average size around 200 nm and a polydispersity index lower than 0.1 were identified. The conditions were optimized to ensure protein encapsulation: a cool temperature, a short processing time, a sufficient internal aqueous phase and careful washing. It appeared that the higher the surfactant concentration in the external aqueous phase was, the smaller the particles, the lower the polydispersity index and the higher the residual amount of surfactant were. For PVA or HSA, the agreement between the convenient surfactant concentration and its critical aggregation concentration could be emphasized. Otherwise, an increased polymer molecular weight led both to a slightly decreased particle size and to a lower polydispersity index. Moreover, multilayer absorption of PVA which does not depend on Poly(lactic-acid) molecular weight was exhibited. Finally, the zeta potential resulted from the polymer molecular weight and the residual PVA.