Synthesis and Characterization of a Polymeric Nanoparticles of a Potent Anticancer Agent (Combretastatin)
An-Najah National University
Background: Pharmaceutical nanotechnology is an emerging technology that proved its effectiveness in decreasing the side effects and improving the therapeutic outcomes of chemotherapeutic drugs. Combretastatin (CA4) is natural and potent antitubuline chemotherapeutic agent but it showed cardiotoxicity. Purpose: The aim of this research was to formulate and characterizeCA4 polymeric nanoparticles (NPs), to assess its release kinetic, and to evaluate the in vitro cytotoxic activity of the obtained NPs. Method: CA4 was synthesized using Perkin reaction. Nano-precipitation and emulsion evaporation methods were used to produce the desired NPs. The obtained NPs were characterized for shape, particle size, zeta-potential, encapsulation efficiency% (EE%), drug loading% (DL%), and drug release. Cytotoxicity and IC50 of the free CA4and the loaded NPs were determined using two cancer cell lines Caco-2 and HeLa. Results: Emulsion evaporation method was capable to produce spherical shaped CA4 loaded NPs with EE% 50.84%, DL% 1.13%, mean average particle size 203.25 nm, and zeta-potential -38.50mV.The NPs showed sustained release pattern. Korsmeyer-Peppas was adopted to describe the release mechanism of CA4 from our NPs, with n value higher than 1, which indicates a Super case II transport. In vitro cytotoxicity on Caco-2 and HeLa cells demonstrated better cytotoxic and IC50 of CA4 loaded NPs than the free CA4. Conclusion:CA4 loaded polymeric NPs were successfully produced and showed satisfactory characteristics such as EE%, particle size and shape, zeta potential, and sustained release pattern. In addition, an improvement in the cytotoxic and IC50 of CA4 loaded NPs was demonstrated. This suggests that these NPs could be used to improve the safety, effectiveness, and patient compliance. However, in vivo studies should be conducted to prove these interesting findings.