Chitosan-zinc-insulin complex incorporated thermosensitive polymer for controlled delivery of basal insulin in vivo.
Chitosan-zinc-insulin complex incorporated thermosensitive polymer for controlled delivery of basal insulin in vivo.
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DOI：
10.1016/j.jconrel.2012.07.035
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发表时间：
2012-10-28
期刊：
影响因子：
--
通讯作者：
Singh J
中科院分区：
文献类型：
--
作者：
Oak M;Singh J
以壳聚糖-胰岛素-锌复合物为载体，设计了一种温度敏感性高分子给药系统（PLA-PEG-PLA）。壳聚糖-锌-胰岛素复合物被优化以通过形成大的复合物来限制胰岛素从递送系统的扩散，从而减少初始突释。在链脲佐菌素诱导的糖尿病大鼠模型上研究了胰岛素缓释系统的体内吸收和生物活性。使用酶联免疫吸附测定（ELISA）定量体内释放的胰岛素的量，并通过其降低糖尿病大鼠血糖水平的能力来确定其生物活性。进行间接ELISA以确定从制剂释放的胰岛素的免疫原性潜力。此外，在体外和体内的生物相容性的输送系统进行了研究，使用MTT法，并通过研究皮肤样品的组织学，分别。与单独的锌-胰岛素或胰岛素相比，壳聚糖-锌-胰岛素复合物显著（P<0.05）减少了胰岛素从聚合物递送系统的初始爆发释放。该输送系统以生物活性形式释放胰岛素约3个月，糖尿病大鼠的血糖水平相应降低。从输送系统释放的胰岛素不会引起任何免疫反应。该递送系统在体外和体内均表现出良好的生物相容性，并且无毒。结果表明，壳聚糖-锌-胰岛素复合物纳入热敏聚合物递送系统可以用作替代传统的每日基础胰岛素治疗。负载壳聚糖-锌-胰岛素复合物的温敏递送系统体内皮下给药后的事件
Thermosensitive polymeric delivery system (PLA-PEG-PLA) loaded with chitosan-zinc-insulin complex was designed for continuous in vivo insulin delivery at basal level for prolonged period after a single subcutaneous injection. Chitosan-zinc-insulin complex was optimized to restrict the diffusion of insulin from the delivery system by forming large complexes and thereby reducing the initial burst release. The in vivo absorption and bioactivity of insulin released from the delivery systems were studied in streptozotocin-induced diabetic rat model. The amount of insulin released in vivo was quantified using Enzyme Linked Immunosorbent Assay (ELISA), and its bioactivity was determined by its ability to reduce the blood glucose levels in diabetic rats. An indirect ELISA was performed to determine the immunogenic potential of insulin released from the formulations. Furthermore, the in vitro and in vivo biocompatibility of the delivery system was studied using an MTT assay, and by studying the histology of skin samples, respectively. Chitosan-zinc-insulin complex significantly (P<0.05) reduced the initial burst release of insulin from the polymeric delivery system in comparison to zinc-insulin or insulin alone. The delivery system released insulin for ~3 months in biologically active form with corresponding reduction in blood glucose levels in diabetic rats. The insulin released from the delivery systems did not provoke any immune response. The delivery systems demonstrated excellent biocompatibility both in vitro and in vivo and were non-toxic. The results indicate that the chitosan-zinc-insulin complex incorporated in the thermosensitive polymeric delivery system can be used as an alternative to the conventional daily basal insulin therapy. Events following subcutaneous administration of chitosan-zinc-insulin complex loaded thermosensitive delivery system in vivo
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