Formulation and characterization of combretastatin A4 loaded PLGA nanoparticles

Abstract

Pharmaceutical nanotechnology is an emerging technology that proved its effectiveness in decreasing the side effects and improving the therapeutic outcomes of chemotherapeutic drugs. Combretastatin A4 (CA4) is a natural potent tubulin polymerization inhibitor. However, it suffers from low water solubility with various side effects. The aim of this study was to formulate and characterize poly(lactide-co-glycolide) (PLGA) nanoparticles loaded with CA4, to assess its release kinetics and to evaluate the in vitro cytotoxic activity of the obtained nanoparticles. CA4 was synthesized according to a previous protocol. Nano-precipitation and emulsion evaporation methods were used to produce the desired drug-loaded PLGA nanoparticles. The obtained nanoparticles were characterized for shape, particle size, zeta-potential, encapsulation efficiency (EE), drug loading (DL) and release kinetics. Cytotoxicity and IC50 of the free CA4 and the loaded nanoparticles were determined using Caco-2 cancer cell lines. PLGA nanoparticles produced by the emulsion evaporation method exhibited higher EE and DL (51% and 1%, respectively) than those prepared by the nanoprecipitation method and hence were selected for further release and cytotoxicity studies. The nanoparticles showed sustained release pattern, following zero-order kinetics. In vitro cytotoxicity studies demonstrated the superiority of CA4 loaded nanoparticles over the corresponding free CA4. CA4 loaded nanoparticles were successfully produced and showed satisfactory characteristics. In addition, an improvement in the cytotoxic and IC50 of CA4 loaded NPs was demonstrated. This suggests that these nanoparticles could be used to improve the safety, effectiveness, and patient compliance, which will be further investigated by in vivo studies