Docetaxel prodrug liposomes for tumor therapy: characterization, in vitro and in vivo evaluation. (3rd May 2016)

• Record Type: Journal Article
• Authors: Ren, Guolian; Liu, Dan; Guo, Weiling; Wang, Menglin; Wu, Chunnuan; Guo, Mengran; Ai, Xiaoyu; Wang, Yongjun; He, Zhonggui
• Is Part Of: Drug delivery. Volume 23:Number 4(2016:May)
• Page Start: 1272
• Page End: 1281
• Publication Date: 2016-05-03
• Subjects: Docetaxel -- liposome -- pharmacokinetics -- prodrug -- redox-responsive; Drug delivery systems -- Periodicals; Drug targeting -- Periodicals; 615.05
• DOI: 10.3109/10717544.2016.1165312
• Languages: English
• ISSNs: 1071-7544

Abstract

Abstract: There is a strong desire to develop docetaxel (DTX) formulation with good therapeutic effectiveness in view of serious adverse reactions of the commercial formulation of DTX (Taxotere®). In this study, a redox-responsive DTX-vitamin E prodrug was successfully formulated into liposomes with the drug loading of 4.14% ± 0.10%. Compared with DTX liposomes, the DTX prodrug liposomes (DPLs) showed good stability for 30-d shelf life and during dilution with different media. In vitro antitumor activity of DPLs on human prostatic carcinoma PC-3 cells and human lung cancer A549 cells was evaluated using cytotoxicity and apoptosis assays. In spite of a decrease in in vitro antitumor activity, the in vivo pharmacokinetic study reveals that DPLs exhibit significantly longer DTX plasma half-life ( t 1/2, 1.38-fold) and higher bioavailability (AUC0− t, 14.49-fold) compared with DTX liposomes. The antitumor activity of DPLs to the A549 tumor xenograft model showed selective accumulation in tumor tissue, significant inhibition the growth of the tumors and a much lower toxicity as seen in body weight loss, compared with DTX-Solution. Taken together, the results showed that DPLs is a promising strategy for DTX antitumor delivery.