title: Comparative study of (Asp)7-CHOL-modified liposome prepared using pre-insertion and post-insertion methods for bone targeting in vivo.
abstract: Specific delivery of drugs to bone tissue is very challenging due to the architecture and structure of bone tissue. A seven-repeat sequence of aspartate, a representative bone-targeting oligopeptide, is preferentially used for targeted therapy for bone diseases. In this study, Asp7-cholesterol((Asp)7-CHOL) was synthesized and (Asp)7-CHOL-modified liposome loaded with doxorubicin (DOX) was successfully prepared using both pre-insertion (pre-L) and post-insertion (post-L) methods. The formulation was optimized according to particle size, zeta potential and the drug-loading efficiency of the liposome. In addition, the bone affinity of the (Asp)7-CHOL-modified liposome was evaluated using a hydroxyapatite (HA) absorption method. The results suggested that (Asp)7-CHOL-modified liposome show excellent HA absorption; pre-L showed slightly higher HA binding than post-L. However, post-L had a higher DOX entrapment efficiency than pre-L. In vivo imaging further demonstrated that pre-L showed a higher bone-targeting efficiency than post-L, which was consistent with in vitro results. In all, (Asp)7-CHOL-modified liposome showed excellent bone-targeting activity, suggesting their potential for use as a drug delivery system for bone disease-targeted therapies.
authors.affiliation: a State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy , West China Hospital, Sichuan University , Chengdu , PR China.
authors.forename: Lijing
authors.initials: L
authors.lastname: Zhang
authors.affiliation: a State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy , West China Hospital, Sichuan University , Chengdu , PR China.
authors.forename: Hua
authors.initials: H
authors.lastname: Cao
authors.affiliation: a State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy , West China Hospital, Sichuan University , Chengdu , PR China.
authors.forename: Jiaxin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: a State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy , West China Hospital, Sichuan University , Chengdu , PR China.
authors.forename: Chengli
authors.initials: C
authors.lastname: Yang
authors.affiliation: a State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy , West China Hospital, Sichuan University , Chengdu , PR China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Hu
authors.affiliation: a State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy , West China Hospital, Sichuan University , Chengdu , PR China.
authors.forename: Huili
authors.initials: H
authors.lastname: Li
authors.affiliation: a State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy , West China Hospital, Sichuan University , Chengdu , PR China.
authors.forename: Wu
authors.initials: W
authors.lastname: Yang
authors.affiliation: a State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy , West China Hospital, Sichuan University , Chengdu , PR China.
authors.forename: Gu
authors.initials: G
authors.lastname: He
authors.affiliation: a State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy , West China Hospital, Sichuan University , Chengdu , PR China.
authors.forename: Xiangrong
authors.initials: X
authors.lastname: Song
authors.affiliation: a State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy , West China Hospital, Sichuan University , Chengdu , PR China.
authors.forename: Aiping
authors.initials: A
authors.lastname: Tong
authors.affiliation: a State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy , West China Hospital, Sichuan University , Chengdu , PR China.
authors.forename: Gang
authors.initials: G
authors.lastname: Guo
authors.affiliation: a State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy , West China Hospital, Sichuan University , Chengdu , PR China.
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.affiliation: a State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy , West China Hospital, Sichuan University , Chengdu , PR China.|b Department of Pharmacy , Hospital of the University of Electronic Science and Technology of China and Sichuan Provincial People's Hospital , Chengdu , PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: a State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy , West China Hospital, Sichuan University , Chengdu , PR China.|b Department of Pharmacy , Hospital of the University of Electronic Science and Technology of China and Sichuan Provincial People's Hospital , Chengdu , PR China.
authors.forename: Jiyan
authors.initials: J
authors.lastname: Liu
authors.affiliation: a State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy , West China Hospital, Sichuan University , Chengdu , PR China.|b Department of Pharmacy , Hospital of the University of Electronic Science and Technology of China and Sichuan Provincial People's Hospital , Chengdu , PR China.
authors.forename: Lulu
authors.initials: L
authors.lastname: Cai
authors.affiliation: a State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy , West China Hospital, Sichuan University , Chengdu , PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zheng
mesh_terms: D000818:Animals; D001842:Bone and Bones; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000737:chemistry*; D004317:Doxorubicin; D016503:Drug Delivery Systems; D017886:Durapatite / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D046529:Microscopy, Electron, Transmission; D015394:Molecular Structure; D009842:Oligopeptides / Q000737:chemistry; D010316:Particle Size
chemical_list: C000626072:Asp7-cholesterol; D008081:Liposomes; D009842:Oligopeptides; D004317:Doxorubicin; D017886:Durapatite; D002784:Cholesterol
keywords: (Asp)7-CHOL; (Asp)7-CHOL-modified liposome; bone targeting; drug delivery system; hydroxyapatite