Zhang Lijing, Cao Hua, Zhang Jiaxin, Yang Chengli, Hu Tingting, Li Huili, Yang Wu, He Gu, Song Xiangrong, Tong Aiping, Guo Gang, Li Rui, Jiang Yu, Liu Jiyan, Cai Lulu, Zheng Yu
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.
J Drug Target. 2017 Feb;25(2):149-155. doi: 10.1080/1061186X.2016.1212201. Epub 2016 Aug 2.
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.
由于骨组织的结构和构造，将药物特异性递送至骨组织极具挑战性。天冬氨酸的七重复序列是一种代表性的骨靶向寡肽，优先用于骨疾病的靶向治疗。在本研究中，合成了天冬氨酸七聚体-胆固醇（(Asp)7-CHOL），并使用预插入法（pre-L）和后插入法（post-L）成功制备了负载阿霉素（DOX）的(Asp)7-CHOL修饰脂质体。根据脂质体的粒径、ζ电位和载药效率对制剂进行了优化。此外，采用羟基磷灰石（HA）吸附法评估了(Asp)7-CHOL修饰脂质体的骨亲和力。结果表明，(Asp)7-CHOL修饰脂质体表现出优异的HA吸附能力；pre-L的HA结合能力略高于post-L。然而，post-L的DOX包封率高于pre-L。体内成像进一步表明，pre-L的骨靶向效率高于post-L，这与体外结果一致。总之，(Asp)7-CHOL修饰脂质体表现出优异的骨靶向活性，表明它们有潜力用作骨疾病靶向治疗的药物递送系统。
