A robust systematic design: Optimization and preparation of polymeric nanoparticles of PLGA for docetaxel intravenous delivery.

ABSTRACT

Poly (lactide-co-glycolide) (PLGA) is a biocompatible, biodegradable, and non-toxic polymer used in a variety of biomedical and pharmaceutical applications. Polymeric nanoparticles prepared from PLGA have been extensively used as delivery vehicles of various chemotherapeutic agents. The variability of PLGA polymer and nanoparticle fabrication process potentially results in variability of particle characteristics. Nanoparticle characteristics determine nanoparticles' performance when used as drug delivery systems. Having control on nanoparticle's characteristics grants control over the fate of nanoparticles and the associated drug. Here, L16 Taguchi experimental design was used to evaluate the effect of polymer characteristics and fabrication variables on PLGA nanoparticles. The design was used to determine an optimized preparation condition for PLGA nanoparticles as an intravenous delivery system for docetaxel. An emulsification-solvent-evaporation method was used to fabricate nanoparticles. Docetaxel concentration, organic phaseaqueous phase ratio, polymer molecular weight, polymer terminus, lactideglycolide ratio, and Poly(vinyl alcohol)(PVA) concentration were selected as main determinants. First two factors were evaluated at 4 levels and the rest at 2 levels. Particle-important characteristics including size, polydispersity index (PDI), surface charge (zeta potential), and docetaxel loading-efficiency were determined. Factors affecting nanoparticle characteristics were ranked according to level of effectiveness. Factors that affected nanoparticle properties with statistical significance were identified. Models to predict nanoparticle characteristics were built. An optimized fabrication method was identified and used to prepare PLGA nanoparticles for docetaxel delivery.