title: Docetaxel prodrug liposomes for tumor therapy: characterization, in vitro and in vivo evaluation.
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 (t1/2, 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.
authors.affiliation: a School of Pharmacy, Shenyang Pharmaceutical University , Shenyang , China .|b School of Pharmacy, Shanxi Medical University , Shanxi , China .
authors.forename: Guolian
authors.initials: G
authors.lastname: Ren
authors.affiliation: c Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University , Shenyang , China .
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
authors.affiliation: a School of Pharmacy, Shenyang Pharmaceutical University , Shenyang , China .
authors.forename: Weiling
authors.initials: W
authors.lastname: Guo
authors.affiliation: a School of Pharmacy, Shenyang Pharmaceutical University , Shenyang , China .
authors.forename: Menglin
authors.initials: M
authors.lastname: Wang
authors.affiliation: d Department of Pharmacy , Tianjin Medical University Cancer Institute and Hospital , Tianjin , China , and.
authors.forename: Chunnuan
authors.initials: C
authors.lastname: Wu
authors.affiliation: a School of Pharmacy, Shenyang Pharmaceutical University , Shenyang , China .
authors.forename: Mengran
authors.initials: M
authors.lastname: Guo
authors.affiliation: e College of Pharmacy, Nankai University , Tianjin , China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Ai
authors.affiliation: a School of Pharmacy, Shenyang Pharmaceutical University , Shenyang , China .
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: a School of Pharmacy, Shenyang Pharmaceutical University , Shenyang , China .
authors.forename: Zhonggui
authors.initials: Z
authors.lastname: He
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D000077143:Docetaxel; D004337:Drug Carriers / Q000494:pharmacology; D006801:Humans; D008081:Liposomes; D008175:Lung Neoplasms / Q000737:chemistry / Q000188:drug therapy*; D053758:Nanoparticles / Q000737:chemistry*; D043823:Taxoids / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000494:pharmacology*; D014810:Vitamin E / Q000737:chemistry* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008081:Liposomes; D043823:Taxoids; D014810:Vitamin E; D000077143:Docetaxel
keywords: Docetaxel; liposome; pharmacokinetics; prodrug; redox-responsive