title: Controlled release of paclitaxel from photocrosslinked chitosan hydrogels and its subsequent effect on subcutaneous tumor growth in mice.
abstract: A photocrosslinkable chitosan (Az-CH-LA) aqueous solution containing paclitaxel resulted in an insoluble hydrogel within 30 s of ultrtaviolet light (UV)-irradiation. About 35-40% of the paclitaxel was released from the paclitaxel-incorporated chitosan hydrogel into phosphate buffered saline (PBS) within 1 day, after which gradual release occurred during 3 days under in vitro non-degradation conditions of the hydrogel. The paclitaxel remaining in the chitosan hydrogel retained its biological activity in vitro for at least 21 days, and was released from the chitosan hydrogel in vivo upon degradation of the hydrogel. The paclitaxel-incorporated Az-CH-LA hydrogel inhibited the growth of subcutaneously induced tumors with Lewis lung cancer (3LL) cells more effectively than those treated with only Az-CH-LA, only paclitaxel, and a non-treated group (control) for at least 11 days. Furthermore, paclitaxel-incorporated chitosan hydrogel markedly reduced the number of CD34-positive vessels in subcutaneous 3LL tumors, indicating a strong inhibition of angiogenesis. These results suggested that application of paclitaxel-incorporated Az-CH-LA hydrogel has an inhibitory activity on angiogenesis and tumor growth.
authors.affiliation: Department of Surgery II, National Defense Medical College, Tokorozawa, Saitama, Japan.
authors.forename: Kiyohaya
authors.initials: K
authors.lastname: Obara
authors.forename: Masayuki
authors.initials: M
authors.lastname: Ishihara
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ozeki
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Ishizuka
authors.forename: Takuya
authors.initials: T
authors.lastname: Hayashi
authors.forename: Shingo
authors.initials: S
authors.lastname: Nakamura
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Saito
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yura
authors.forename: Takemi
authors.initials: T
authors.lastname: Matsui
authors.forename: Hidemi
authors.initials: H
authors.lastname: Hattori
authors.forename: Bonpei
authors.initials: B
authors.lastname: Takase
authors.forename: Miya
authors.initials: M
authors.lastname: Ishihara
authors.forename: Makoto
authors.initials: M
authors.lastname: Kikuchi
authors.forename: Tadaaki
authors.initials: T
authors.lastname: Maehara
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D018827:Carcinoma, Lewis Lung / Q000098:blood supply / Q000473:pathology / Q000517:prevention & control*; D045744:Cell Line, Tumor; D048271:Chitosan / Q000737:chemistry*; D003692:Delayed-Action Preparations; D004058:Diffusion; D004337:Drug Carriers / Q000737:chemistry*; D004355:Drug Stability; D042783:Endothelial Cells / Q000187:drug effects; D020100:Hydrogels / Q000737:chemistry*; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D017239:Paclitaxel / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D010777:Photochemistry; D012878:Skin Neoplasms / Q000098:blood supply / Q000473:pathology / Q000517:prevention & control*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D020100:Hydrogels; D048271:Chitosan; D017239:Paclitaxel