Preparation, Characterization and Evaluation of Docetaxel-loaded, Folate-conjugated PEG-liposomes

Abstract

  For the purpose of enhancing the anticancer potency of docetaxel, a novel excipient, cholesterol-PEG-folate (α-(3.beta) cholest-5-en-3-ω-folic acid-poly (oxy-1, 2-ethanediyl)), was synthesized and used for the preparation of liposomes (folate-conjugated PEG-liposomes). The in vitro release properties, in vitro cytotoxicity, in vivo pharmacokinetics and distribution, as well as in vivo potency of the liposomes were evaluated. These liposomes were able to control the release of the loaded drug. Docetaxel-loaded, folate-conjugated PEG-liposomes were more cytotoxic to MCF-7cells than ordinary PEG-liposomes. The pharmacokinetic parameters of folate-conjugated PEG-liposomes were studied in rats. Compared to docetaxel solution, the folate-conjugated PEG-liposomes enhanced the t_1/2 of docetaxel by 6.74-fold. The biodistributions of docetaxel in the heart, brain and kidneys decreased when delivered in liposomes. The folate-conjugated PEG-liposomes could significantly enhance tumor accumulation of docetaxel and antitumor activity in tumor-bearing mice (p<0.05). The precent results indicate that these folate-conjugated PEG-liposomes might enhance the potency while preventing the side effects of docetaxel.