title: Efficient drug delivery of Paclitaxel glycoside: a novel solubility gradient encapsulation into liposomes coupled with immunoliposomes preparation.
abstract: Although the encapsulation of paclitaxel into liposomes has been extensively studied, its significant hydrophobic and uncharged character has generated substantial difficulties concerning its efficient encapsulation into the inner water core of liposomes. We found that a more hydrophilic paclitaxel molecule, 7-glucosyloxyacetylpaclitaxel, retained tubulin polymerization stabilization activity. The hydrophilic nature of 7-glucosyloxyacetylpaclitaxel allowed its efficient encapsulation into the inner water core of liposomes, which was successfully accomplished using a remote loading method with a solubility gradient between 40% ethylene glycol and Cremophor EL/ethanol in PBS. Trastuzumab was then conjugated onto the surface of liposomes as immunoliposomes to selectively target human epidermal growth factor receptor-2 (HER2)-overexpressing cancer cells. In vitro cytotoxicity assays revealed that the immunoliposomes enhanced the toxicity of 7-glucosyloxyacetylpaclitaxel in HER2-overexpressing cancer cells and showed more rapid suppression of cell growth. The immunoliposomes strongly inhibited the tumor growth of HT-29 cells xenografted in nude mice. Notably, mice survived when treated with the immunoliposomes formulation, even when administered at a lethal dose of 7-glucosyloxyacetylpaclitaxel in vivo. This data successfully demonstrates immunoliposomes as a promising candidate for the efficient delivery of paclitaxel glycoside.
authors.affiliation: Department of Biotechnology, Graduate School of Natural Science and Technology, Okayama University, Okayama, Japan.
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Shigehiro
authors.affiliation: Department of Biotechnology, Graduate School of Natural Science and Technology, Okayama University, Okayama, Japan.
authors.forename: Tomonari
authors.initials: T
authors.lastname: Kasai
authors.affiliation: Department of Biotechnology, Graduate School of Natural Science and Technology, Okayama University, Okayama, Japan.
authors.forename: Masaharu
authors.initials: M
authors.lastname: Murakami
authors.affiliation: Department of Biotechnology, Graduate School of Natural Science and Technology, Okayama University, Okayama, Japan.
authors.forename: Sreeja C
authors.initials: SC
authors.lastname: Sekhar
authors.affiliation: Department of Biotechnology, Graduate School of Natural Science and Technology, Okayama University, Okayama, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Tominaga
authors.affiliation: Department of Biotechnology, Graduate School of Natural Science and Technology, Okayama University, Okayama, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Okada
authors.affiliation: Department of Biotechnology, Graduate School of Natural Science and Technology, Okayama University, Okayama, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kudoh
authors.affiliation: Department of Biotechnology, Graduate School of Natural Science and Technology, Okayama University, Okayama, Japan.
authors.forename: Akifumi
authors.initials: A
authors.lastname: Mizutani
authors.affiliation: Department of Biotechnology, Graduate School of Natural Science and Technology, Okayama University, Okayama, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Murakami
authors.affiliation: Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, Maryland, United States of America.
authors.forename: David S
authors.initials: DS
authors.lastname: Salomon
authors.affiliation: Ensuiko Sugar Refining Co., Ltd., Tokyo, Japan.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Mikuni
authors.affiliation: Faculty of Life Science, Kurashiki University of Science and the Arts, Kurashiki, Japan.
authors.forename: Tadakatsu
authors.initials: T
authors.lastname: Mandai
authors.affiliation: Faculty of Science, Okayama University of Science, Okayama, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Hamada
authors.affiliation: Department of Biotechnology, Graduate School of Natural Science and Technology, Okayama University, Okayama, Japan.
authors.forename: Masaharu
authors.initials: M
authors.lastname: Seno
mesh_terms: D000818:Animals; D004337:Drug Carriers; D005260:Female; D006027:Glycosides / Q000008:administration & dosage*; D019073:HT29 Cells; D006801:Humans; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry; D012995:Solubility
chemical_list: D004337:Drug Carriers; D006027:Glycosides; D008081:Liposomes; D017239:Paclitaxel