title: Evaluation of glycosylated docetaxel-encapsulated liposomes prepared by remote loading under solubility gradient.
abstract: Docetaxel comprises one of the most effective anti-cancer drugs despite of serious side effects. Liposomes encapsulation is practically feasible to deliver the drug. However, due to the significant hydrophobicity, docetaxel will be integrated into the lipid bilayer resulting in poor encapsulation capacity. Here, we evaluated a remote loading strategy using a solubility gradient made between the two solvents for 7-glucosyloxyacetyldocetaxel, which has enhanced water solubility of docetaxel with a coupled glucose moiety. Therefore, 7-glucosyloxyacetyldocetaxel was more effectively encapsulated into liposomes with 71.0% of encapsulation efficiency than docetaxel. While 7-glucosyloxyacetyldocetaxel exhibited 90.9% of tubulin stabilisation activity of docetaxel, 7-glucosyloxyacetyldocetaxel encapsulated in liposomes significantly inhibited the growth of tumour in vivo with side effects less than unencapsulated drug. Collectively, the encapsulation of 7-glucosyloxyacetyldocetaxel into liposomes by remote loading under the solubility gradient is considered to be a promising application to prepare practical drug delivery system.
authors.affiliation: a Department of Medical Bioengineering, Graduate School of Natural Science and Technology , Okayama University , Okayama , Japan ;|b Japan Society for the Promotion of Science , Tokyo , Japan ;
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Shigehiro
authors.affiliation: a Department of Medical Bioengineering, Graduate School of Natural Science and Technology , Okayama University , Okayama , Japan ;
authors.forename: Wenjia
authors.initials: W
authors.lastname: Zhai
authors.affiliation: a Department of Medical Bioengineering, Graduate School of Natural Science and Technology , Okayama University , Okayama , Japan ;
authors.forename: Arun
authors.initials: A
authors.lastname: Vaidyanath
authors.affiliation: a Department of Medical Bioengineering, Graduate School of Natural Science and Technology , Okayama University , Okayama , Japan ;
authors.forename: Junko
authors.initials: J
authors.lastname: Masuda
authors.affiliation: a Department of Medical Bioengineering, Graduate School of Natural Science and Technology , Okayama University , Okayama , Japan ;
authors.forename: Akifumi
authors.initials: A
authors.lastname: Mizutani
authors.affiliation: a Department of Medical Bioengineering, Graduate School of Natural Science and Technology , Okayama University , Okayama , Japan ;
authors.forename: Tomonari
authors.initials: T
authors.lastname: Kasai
authors.affiliation: a Department of Medical Bioengineering, Graduate School of Natural Science and Technology , Okayama University , Okayama , Japan ;
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Murakami
authors.affiliation: c Faculty of Science , Okayama University of Science , Okayama , Japan ;
authors.forename: Hiroki
authors.initials: H
authors.lastname: Hamada
authors.affiliation: d Mouse Cancer Genetics Program , National Cancer Institute , Frederick , MD , USA ;
authors.forename: David S
authors.initials: DS
authors.lastname: Salomon
authors.affiliation: e Ensuiko Sugar Refining Co. Ltd , Tokyo , Japan ;
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Mikuni
authors.affiliation: f Faculty of Life Science , Kurashiki University of Science and the Arts , Kurashiki , Japan.
authors.forename: Yuhki
authors.initials: Y
authors.lastname: Seno
authors.affiliation: f Faculty of Life Science , Kurashiki University of Science and the Arts , Kurashiki , Japan.
authors.forename: Tadakatsu
authors.initials: T
authors.lastname: Mandai
authors.affiliation: a Department of Medical Bioengineering, Graduate School of Natural Science and Technology , Okayama University , Okayama , Japan ;
authors.forename: Masaharu
authors.initials: M
authors.lastname: Seno
mesh_terms: D000107:Acetylation; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D000077143:Docetaxel; D004339:Drug Compounding / Q000379:methods; D006031:Glycosylation; D006801:Humans; D008081:Liposomes / Q000737:chemistry; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D012995:Solubility; D043823:Taxoids / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D043823:Taxoids; D000077143:Docetaxel
keywords: Docetaxel; glycosylated docetaxel; liposome; remote loading method; solubility gradient