Development and Characterization of Docetaxel-Loaded Nanoparticles for Docetaxel-Resistant Castration-Resistant Prostate Cancer

The objective of the present study is to develop novel docetaxel nanoparticles to treat docetaxel-resistant castration-resistant prostate cancer. Oils and surfactants used to prepare docetaxel nanoparticles were selected based on the solubility test. Docetaxel nanoparticles were prepared by an emulsion method using Migloyl 812 as the oil phase and D-alpha-tocopheryl polyethylene glycol 1000 succinate as the surfactant phase. The nanoparticles were characterized in terms of particle size, zeta potential, polydispersity index, long-term stability, drug loading, drug entrapment efficiency, in vitro release study, differential scanning calorimetry analysis, and cytotoxicity studies in the sensitive and resistant castration-resistant prostate cancer cell lines of PC3 and DU145. All tested nanoparticles had particle size less than 120 nm with narrow size distribution. Docetaxel nanoparticles were physically stable at 4 degrees C over six months. Drug entrapment efficiency was over 93%, with drug loading of 3.5% (drug/total excipients, w/w). The result of differential scanning calorimetry showed that docetaxel was present as amorphous in docetaxel nanoparticles. The cytotoxicity studies demonstrated that the IC50 values of docetaxel nanoparticles and free docetaxel for the sensitive cell lines were comparable. For the docetaxel-resistant cell lines, docetaxel nanoparticles significantly reduced the IC50 values when compared to those of free docetaxel. Therefore, docetaxel nanoparticles have potential to treat docetaxel-resistant castration-resistant prostate cancer.