Comparative study of (Asp)7-CHOL-modified liposome prepared using pre-insertion and post-insertion methods for bone targeting in vivo
Comparative study of (Asp)7-CHOL-modified liposome prepared using pre-insertion and post-insertion methods for bone targeting in vivo
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DOI：
10.1080/1061186x.2016.1212201
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发表时间：
2017-01-01
影响因子：
4.5
通讯作者：
Zheng, Yu
中科院分区：
文献类型：
--
作者：
Zhang, Lijing;Cao, Hua;Zheng, Yu
由于骨组织的结构和结构，将药物定向输送到骨组织是非常具有挑战性的。天冬氨酸是一种具有代表性的骨靶向寡肽，其7个重复序列被优先用于骨疾病的靶向治疗。本研究合成了天冬氨酸7-胆固醇((Asp)7-Chol)，并采用预先(L前)和后(L后)两种方法成功地制备了阿霉素(DOX)的(Asp)7-Chol修饰脂质体。根据脂质体的粒径、Zeta电位和载药率对处方进行优化。此外，用羟基磷灰石(HA)吸收法评价了(Asp)7-Chol修饰脂质体的骨亲和力。结果表明，(Asp)7-Chol修饰的脂质体具有良好的HA吸附性能，L前的HA结合率略高于L-L后。然而，L给药后的包封率高于给药前。体内成像进一步表明，L治疗前的骨靶向效率高于L治疗后，这与体外实验结果一致。总之，(Asp)7-Chol修饰的脂质体显示出良好的骨靶向活性，这表明它们作为骨病靶向治疗的药物输送系统具有潜力。
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.