Design and evaluation of biodegradable, biosensitive in situ gelling system for pulsatile delivery of insulin
Design and evaluation of biodegradable, biosensitive in situ gelling system for pulsatile delivery of insulin
复制标题
DOI：
10.1016/j.biomaterials.2007.01.007
复制
发表时间：
2007-04-01
期刊：
影响因子：
14
通讯作者：
Kumar, M. N. V. Ravi
中科院分区：
文献类型：
--
作者：
Kashyap, N.;Viswanad, B.;Kumar, M. N. V. Ravi
以壳聚糖为基质，制备了可生物降解的葡萄糖敏感性胰岛素脉冲释药原位凝胶系统。溶胶/凝胶的溶胀性能，流变学，质地分析和水含量进行了彻底的表征。所开发的葡萄糖敏感凝胶在体外对不同的葡萄糖浓度作出反应，表明它们具有作为环境敏感系统的能力。胰岛素加载到凝胶上进行了优化，并发现影响这些凝胶的流变学行为，用于体外的最终制剂含有1 IU/200 μ l的溶胶。这些凝胶在体外响应于葡萄糖浓度以脉冲方式释放包封的胰岛素。此外，当以3 IU/kg的剂量评价所述制剂在链脲霉素诱导的糖尿病大鼠中的体内功效时，证明了它们响应于葡萄糖浓度而释放胰岛素的能力，并且优选比用作对照的皮下给予的普通胰岛素制剂好得多。总之，这些初步结果表明，生物敏感性壳聚糖原位胶凝系统有很大的潜力作为胰岛素的脉冲输送系统。(c)2007爱思唯尔有限公司保留所有权利。
Biodegradable glucose-sensitive in situ gelling system based on chitosan for pulsatile delivery of insulin was developed. The sols/gels were thoroughly characterized for swelling properties, rheology, texture analysis and water content. The developed glucose-sensitive gels responded to varied glucose concentrations in vitro indicating their ability to function as environment-sensitive systems. Insulin load onto the gels was optimized and was found to affect the rheological behavior of these gels, the final preparation used for in vitro contained 1 IU/200 mu l of the sol. These gels released the entrapped insulin in a pulsatile manner in response to the glucose concentration in vitro. Furthermore, the formulations when evaluated for their in vivo efficacy in streptozotocin-induced diabetic rats at a dose of 3 IU/kg, demonstrated their ability to release insulin in response to glucose concentration and were preferred much better against subcutaneously given plain insulin formulation used as the control. Together, these preliminary results indicate that biosensitive chitosan in situ gelling systems have substantial potential as pulsatile delivery systems for insulin. (c) 2007 Elsevier Ltd. All rights reserved.