Influence of the Formulation Parameters on the Particle Size and Encapsulation Efficiency of Resveratrol in PLA and PLA-PEG Blend Nanoparticles: A Factorial Design.

Polymeric nanoparticles are colloidal systems that promote protection and modification of physicochemical characteristics of a drug and that also ensure controlled and extended drug release. This paper reports a 2(3) factorial design study to optimize poly(lactide) (PLA) and poly(lactide)-polyethylene glycol (PLA-PEG) blend nanoparticles containing resveratrol (RVT) for prolonged release. The independent variables analyzed were solvent composition, surfactant concentration and ratio of aqueous to organic phase (two levels each factor). Mean particle size and RVT encapsulation efficiency were set as the dependent variables. The selected optimized parameters were set as organic phase comprised of a mixture of dichloromethane and ethyl acetate, 1% of surfactant polyvinyl alcohol and a 3:1 ratio of aqueous to organic phase, for both PLA and PLA-PEG blend nanoparticles. This formulation originated nanoparticles with size of 228 ± 10 nm and 185 ± 70 nm and RVT encapsulation efficiency of 82 ± 10% and 76 ± 7% for PLA and PLA-PEG blend nanoparticles, respectively. The in vitro release study showed a biphasic pattern with prolonged RVT release and PEG did not influence the RVT release. The in vitro release data were in favor of Higuchi-diffusion kinetics for both nanoformulations and the Kossmeyer-Peppas coefficient indicated that anomalous transport was the main release mechanism of RVT. PLA and PLA-PEG blend nanoparticles produced with single emulsion-solvent evaporation technology were found to be a promising approach for the incorporation of RVT and promoted its controlled release. The factorial design is a tool of great value in choosing formulations with optimized parameters.