Central Composite Design for Optimization of Zoledronic Acid Loaded PLGA Nanoparticles

Purpose Zoledronic acid (ZA) is one of the drugs used clinically for the treatment of osteoporosis, and its therapeutic effect is due to the inhibition of osteoclastic cells leading to bone resorption. The aim of this study is developing an optimization method for poly(lactide-co-glycolide) (PLGA) nanoparticles of ZA which is intended for local application to enable guided bone regeneration. Methods Three formulation parameters (ZA content, PLGA/Pluronic F68 ratio, and organic to aqueous phase ratio) were optimized to evaluate their effects on particle size (Y-1), polydispersity index (PDI) (Y-2), zeta potential (Y-3), and entrapment efficiency (Y-4) utilizing central composite experimental design (CCD). Interaction among components was studied by Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), and X-ray diffraction analysis. Morphology of nanoparticles was visualized with transmission electron microscopy (TEM). Stability studies of nanoparticles were also carried out for 6 months. Results The results revealed that formulation parameters significantly affected Y-1, Y-2, Y-3, and Y-4 of the nanoparticles. The developed quadratic model showed high correlation (R-2 > 0.84) between predicted response and evaluated parameters. Spherical nanoparticles with low mean particle size (< 106.0 nm) and high encapsulation efficiency (> 39.54%) were obtained with the optimized nanoparticle formulation and maintained colloidal stability for 6 months. Conclusions The use of CCD for the optimization of ZA-loaded PLGA nanoparticles has provided accessibility to the formulation with optimum properties with less experimental procedure and therefore presents an important model for predicting the properties of nanoparticles prepared with PLGA polymer commonly used in the field of drug delivery.