Novel Nanoparticle Formulation For Cancer Therapy

Cancer is the leading cause of death worldwide. Docetaxel is one of the best antineoplastic drugs in past decades, which has excellent therapeutic effects against a wide spectrum of cancers. However its applications are limited due to the current formulation for docetaxel, which is associated with severe side effects in humans. Drug-loaded nanoparticles can provide a way of sustained and controlled drug delivery to improve the therapeutic effects and reduce the side effects. In this study, we formulated docetaxel-loaded nanoparticles with two kinds of novel biodegradable copolymers, which were synthesized by us recently, in order to achieve high drug encapsulation efficiency, desired drug release profiles, good biocompability, and improvement of drug permeability across cancer cell membranes, which could result in high cellular uptake and good cytotoxicity.Synthetic biodegradable polymers have been widely utilized as the polymeric matrix materials of drug delivery systems. Traditional linear polyesters such as PCL, PLA and PLGA, which have been approved by FDA, have disadvantages to be used for drug delivery systems such as too high hydrophobicity and too slow degradation. Thus, the surface modification on these materials must be done to improve their quality. TPGS has amphiphilic structure and large surface area, which make it become an excellent solubilizer, emulsifier and bioavailability enhancer of hydrophobic drugs. We took such advantages of TPGS to synthesize PCL-PLA-TPGS and PLGA-TPGS, which could be expected to improve the formulation for docetaxel. The obtained copolymers were characterized by NMR, FT-IR, GPC and TGA.The docetaxel-loaded nanoparticles were prepared by a modified solvent extraction/evaporation method and characterized with FESEM, DSC, HPLC, LLS, and Zeta potential analyzer. The results revealed that the drug EE of nanoparticles was improved greatly with 0.03% TPGS as emulsifier. The size of such nanoparticles was found to be around 200 nm. The nanoparticles were spherical in shape and appeared smooth within the FESEM resolution level.The drug-loaded nanoparticles could release drug at an appropriate rate, which could meet the therapeutic needs better. In vitro cellular uptakes of such nanoparticles were investigated by CLSM, demonstrating the fluorescence PLGA-TPGS nanoparticles could be internalized by human cervix carcinoma cells (HeLa). MTT assay indicated that drug-free nanoparticles were biocompatible, and the docetaxel-loaded nanoparticles had significant cytotoxicity against Hela cells. The cytotoxicity against HeLa cells for drug-loaded nanoparticles was in time- and concentration-dependent manner.In conclusion, two kinds of copolymers could be acted as a novel and potential biocompatible polymeric matrix material applicable to nanoparticle-based drug delivery system for cancer chemotherapy.