title: Improved Bioavailability and Antitumor Effect of Docetaxel by TPGS Modified Proniosomes: In Vitro and In Vivo Evaluations.
abstract: A novel oral drug delivery system, TPGS modified docetaxel proniosomes (DTX-TPGS-PNs), was designed to enhance the oral bioavailability and antitumor efficiency of the poorly water-soluble drug docetaxel. DTX-TPGS-PN niosomes were 93 ± 6.5 nm in size, -18.53 ± 1.65 mV in zeta potential and exhibited spherical morphology, with an encapsulation efficiency of 97.31 ± 0.60%. The system showed sustained release in both simulated gastric and intestinal fluid. The results of caco-2 monolayer, everted gut sac model and improved single-pass intestinal perfusion model transport studies showed that DTX-TPGS-PN niosomes could significantly improve the absorption of DTX. The pharmacokinetics study suggested the absolute bioavailability of DTX-TPGS-PN niosomes were 7.3 times that of DTX solution. In addition, a higher antitumor efficacy than DTX solution was demonstrated in MCF-7 and MDA-MB-231 cells in vitro and in MCF-7 tumor-bearing mice model in vivo. Our results demonstrated DTX-TPGS-PN is promising in enhancing the bioavailability and efficiency of poorly water-soluble drug DTX, and the potential of proniosomes as stable precursors for oral drug delivery.
authors.affiliation: Murad Research Center for Modernized Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People's Republic of China.
authors.forename: Helong
authors.initials: H
authors.lastname: Liu
authors.affiliation: Murad Research Center for Modernized Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People's Republic of China.
authors.forename: Liangxing
authors.initials: L
authors.lastname: Tu
authors.affiliation: Murad Research Center for Modernized Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People's Republic of China.
authors.forename: Yongxin
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Murad Research Center for Modernized Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People's Republic of China.
authors.forename: Zefang
authors.initials: Z
authors.lastname: Dang
authors.affiliation: Murad Research Center for Modernized Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People's Republic of China.
authors.forename: Luting
authors.initials: L
authors.lastname: Wang
authors.affiliation: Murad Research Center for Modernized Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People's Republic of China.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Du
authors.affiliation: Murad Research Center for Modernized Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People's Republic of China.
authors.forename: Jianfang
authors.initials: J
authors.lastname: Feng
authors.affiliation: Murad Research Center for Modernized Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People's Republic of China.
authors.forename: Kaili
authors.initials: K
authors.lastname: Hu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D001682:Biological Availability; D001943:Breast Neoplasms / Q000188:drug therapy; D018938:Caco-2 Cells; D004195:Disease Models, Animal; D000077143:Docetaxel; D004337:Drug Carriers / Q000008:administration & dosage / Q000378:metabolism*; D006801:Humans; D008081:Liposomes / Q000008:administration & dosage / Q000378:metabolism*; D051379:Mice; D043823:Taxoids / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D016896:Treatment Outcome; D014810:Vitamin E / Q000008:administration & dosage / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008081:Liposomes; D043823:Taxoids; D014810:Vitamin E; D000077143:Docetaxel; C014225:tocophersolan