Injectable and biodegradable phospholipid-based phase separation gel for sustained delivery of insulin
Injectable and biodegradable phospholipid-based phase separation gel for sustained delivery of insulin
复制标题
用于持续输送胰岛素的可注射且可生物降解的磷脂基相分离凝胶
DOI：
10.1016/j.colsurfb.2019.01.003
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Zhang Zhirong
中科院分区：
文献类型：
--
作者：
Zhang Ting;Luo Jingwen;Peng Qiang;Dong Jianxia;Wang Yunuo;Gong Tao;Zhang Zhirong
长期每日注射胰岛素治疗糖尿病，往往给患者带来极大痛苦。为了减少注射频率和提高患者的依从性，在本研究中配制了可注射的原位形成的基于磷脂的相分离凝胶（PPSG）。将胰岛素负载于PPSG中进行缓释和控释，在释放过程中保持胰岛素的生物活性。PPSG在体内的原位形成和降解行为表明，溶剂交换可能是其相变的驱动力，磷脂囊泡的形成和破裂可能是药物释放和凝胶降解的机制。在异物反应研究中，PPSG植入物被证明是可生物降解的，并且炎症和纤维化反应的程度可以通过增加磷脂含量来降低。通过对胰岛素在PPSG中的释药特性和生物活性的研究，验证了胰岛素在PPSG中的适用性。结果表明，载胰岛素的PPSG在糖尿病大鼠体内表现出持续的药物释放行为和持久的降血糖作用。PPSG具有良好的生物相容性和生物降解性，有望作为胰岛素缓释系统，有效提高患者依从性。
Long-term and daily injection of insulin for the treatment of diabetes mellitus often bring great suffering to patients. In order to reduce injection frequency and improve patient compliance, an injectable in-situ forming phospholipid-based phase separation gel (PPSG) was formulated in the present study. Insulin was loaded into PPSG for sustained and controlled delivery, which could maintain the bioactivity of insulin during its release process. The in-situ formation and degradation behavior of PPSGin vivoindicated that solvent exchange could be the driving force for phase transition and that phospholipid vesicle formation and burst could be the mechanism of drug release and gel degradation. In the foreign body response study, PPSG implants were demonstrated to be biodegradable, and the degree of inflammation and fibrotic responses could be decreased by increasing the phospholipid content. The applicability of insulin on PPSG was justified by studying the drug release property and the bioactivity of insulin in PPSG. As a result, the insulin-loaded PPSG showed a sustained drug release behavior and a long-lasting hypoglycemic effect in diabetic rats. In conclusion, PPSG is of good biocompatibility and biodegradability, which is promising to serve as a sustained insulin delivery system and improve patient compliance effectively.