Influence of process conditions on the mean size of PLGA nanoparticles

Investigation was carried out to determine the influence of process conditions on the volume mean size of PLGA nanoparticles intended as drug delivery vehicle for an injection formula of protein type therapeutic agent. Nanoparticles were produced by double emulsion-solvent evaporation method to encapsulate bovine serum albumin into the PLGA matrix material. At first aqueous BSA solution was dispersed by sonication into an organic phase composed of dichloromethane as solvent and dissolved PLGA. This first emulsion was dispersed in a second aqueous phase containing PVA emulsifier. Solid nanoparticles were obtained by evaporating the dichloromethane from the droplets. Size distribution of particles was determined by dynamic light scattering. It was found that volume mean particle size was influenced by several process variables, such as PVA concentration in the external phase, PLGA concentration in the organic phase, BSA concentration in the inner phase, volume ratio of the external and intermediate phases, and the time of sonication during the second emulsification. To elucidate their effects a 5-factorial 3-level experimental design and statistical analysis were carried out. Relationship between the mean particle size and process parameters was proposed.