Lifang Wu1, Cui Tang, Chunhua Yin. 1. State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China. wlfang2008@sina.com
Abstract
BACKGROUND: As a promising anticancer drug, severe side-effects of current clinical formulations for paclitaxel have restricted its use, developing a better technical-economical formulation for paclitaxel delivery is needed. METHOD: In this study, the compound of folate-poly(ethylene glycol) (PEG)-phosphatidylethanolamine was synthesized and characterized with Fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy. The solid-liquid lipid nanoparticle (SLLN) for paclitaxel modified with folate and poly(ethylene glycol) (folate-PEG-SLLN) was prepared and characterized. Morphology of folate-PEG-SLLN was examined by transmission electron microscopy. The particle size and zeta potential were performed by Zetapals. Encapsulation efficiency was analyzed by HPLC. The in vitro drug release of paclitaxel was investigated via membrane dialysis. The in vivo pharmacokinetics was measured with male Sprague-Dawley rats. Treatment efficiency was investigated with the mouse with sarcoma180 ascites tumor. RESULTS: Paclitaxel loaded on the newly designed binary SLLN showed a longer and sustained in vitro releasing property. More importantly, S180 tumor-bearing mice treated with paclitaxel-loaded SLLN exhibited higher tumor inhibition rate, comparing with animals administered with paclitaxel injection alone (45.3% and 37.3%, respectively). CONCLUSION: The newly developed paclitaxel delivery system may have improved in vivo antitumor activity. The results demonstrated a great interest to use folate-mediated SLLN as a prospective drug delivery system for paclitaxel.
BACKGROUND: As a promising anticancer drug, severe side-effects of current clinical formulations for paclitaxel have restricted its use, developing a better technical-economical formulation for paclitaxel delivery is needed. METHOD: In this study, the compound of folate-poly(ethylene glycol) (PEG)-phosphatidylethanolamine was synthesized and characterized with Fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy. The solid-liquid lipid nanoparticle (SLLN) for paclitaxel modified with folate and poly(ethylene glycol) (folate-PEG-SLLN) was prepared and characterized. Morphology of folate-PEG-SLLN was examined by transmission electron microscopy. The particle size and zeta potential were performed by Zetapals. Encapsulation efficiency was analyzed by HPLC. The in vitro drug release of paclitaxel was investigated via membrane dialysis. The in vivo pharmacokinetics was measured with male Sprague-Dawley rats. Treatment efficiency was investigated with the mouse with sarcoma180 ascites tumor. RESULTS:Paclitaxel loaded on the newly designed binary SLLN showed a longer and sustained in vitro releasing property. More importantly, S180 tumor-bearing mice treated with paclitaxel-loaded SLLN exhibited higher tumor inhibition rate, comparing with animals administered with paclitaxel injection alone (45.3% and 37.3%, respectively). CONCLUSION: The newly developed paclitaxel delivery system may have improved in vivo antitumor activity. The results demonstrated a great interest to use folate-mediated SLLN as a prospective drug delivery system for paclitaxel.