School of Chinese Medicine, Hong Kong Baptist University, 7 Baptist University Road, Kowloon Tong, Kowloon, Hong Kong, China.
Curr Pharm Des. 2018 Feb 12;23(39):6079-6085. doi: 10.2174/1381612823666170509123844.
Repeated administrations of insulin injection on daily basis evoke pain and numerous complications with adverse effects on the diabetic patients' life quality. Moreover, wearing insulin pump is also associated with several problems of diabetic ketoacidosis, catheter site infection, contact dermatitis and high cost.
We have developed an in situ gel system, consisting of insulin-loaded liposomes dispersed within a thermoreversible gel (Pluronic® F127 gel), which increases the duration of insulin action for the treatment of diabetes. Vesicular phospholipid gel technique was used to encapsulate the insulin into liposomes.
The resulting liposomal gel formulation had a longer drug-release period in vitro than a free insulin solution or liposomes and Pluronic® F127 gel individually. Furthermore, the addition of liposomes to the Pluronic® F127 gel improved the stability of the encapsulated insulin at a physiological temperature. In vivo study was performed to investigate the bioactivity and absorption of insulin released from the liposomal gel and other formulations. The liposomal gel released insulin into the bloodstream continuously for up to 7 days and significantly enhanced drug bioavailability compared to insulin released from liposomes or Pluronic® F127 gel individually. Blood glucose levels were reduced for up to 4 days. Histology data demonstrated excellent biocompatibility of the Pluronic® F127 gel-based delivery systems, with no observable inflammatory response in rat subcutaneous tissues.
Obtained results show that the insulin-loaded liposomes dispersed within Pluronic® F127 gel can be used as a long-acting drug delivery system, and replacement for conventional insulin therapy.
每天多次注射胰岛素会引起疼痛，并带来许多并发症，对糖尿病患者的生活质量产生不良影响。此外，佩戴胰岛素泵也会引起糖尿病酮症酸中毒、导管部位感染、接触性皮炎和高成本等问题。
我们开发了一种原位凝胶系统，由负载胰岛素的脂质体分散在热可逆凝胶（Pluronic® F127 凝胶）中组成，该系统可增加胰岛素的作用持续时间，用于治疗糖尿病。采用囊泡磷脂凝胶技术将胰岛素包裹在脂质体中。
与游离胰岛素溶液或脂质体和 Pluronic® F127 凝胶单独使用相比，所得脂质体凝胶制剂具有更长的体外药物释放期。此外，将脂质体添加到 Pluronic® F127 凝胶中可以提高在生理温度下包封胰岛素的稳定性。进行了体内研究，以研究从脂质体凝胶和其他制剂中释放的胰岛素的生物活性和吸收。脂质体凝胶持续将胰岛素释放到血液中长达 7 天，与单独从脂质体或 Pluronic® F127 凝胶中释放的胰岛素相比，显著提高了药物的生物利用度。血糖水平降低了长达 4 天。组织学数据表明，基于 Pluronic® F127 凝胶的递药系统具有良好的生物相容性，在大鼠皮下组织中没有观察到炎症反应。
研究结果表明，负载胰岛素的脂质体分散在 Pluronic® F127 凝胶中可以用作长效药物递送系统，替代常规胰岛素治疗。
