GLUCOSE SENSITIVE MEMBRANES IN THE DELIVERY OF INSULIN

控制胰岛素的葡萄糖敏感膜的进一步发展 以随葡萄糖浓度变化的速率递送是该公司的目标 拟开展的研究。生产可膨胀聚合物的原始概念 以响应升高的葡萄糖浓度并允许更大的运输 已经证实了从储藏室中提取的胰岛素。这些工具的效用 在接近其最终在胰岛素中使用的条件下的膜 投放工具将在拟议的研究中确定。的目标是 新的研究是为了测量胰岛素通过葡萄糖的转运。 目前的敏感膜以及改进的设计 测试膜控制胰岛素能力的条件 以一种生理上有用的方式交付。具体地说，以下是 参数将被测量：在没有胰岛素渗透率的情况下 葡萄糖和在一系列恒定的， 生理上相关的葡萄糖浓度；变化的动力学 由受控的葡萄糖增减引起的通透性 水平；葡萄糖反应的重复性；最后， 膜的葡萄糖响应能力的长期稳定性。 胰岛素转运研究将在无碘125I胰岛素中进行 用我们实验室开发的新程序准备，并通过 独立方法(免疫测定法或比色法)。一款特别设计的 运输细胞允许葡萄糖溶液被泵过 将使用下游车厢。辐射诱导聚合 到目前为止成功使用的冷冻单体溶液的比例将继续 用于膜的制备。胰岛素转运的优化 将对目前的葡萄糖敏感膜的性质进行研究 通过设计、制备和表征由 膜的每种化学成分的不同比例。 溶胀性和力学性能均有改善的膜的制备 将用新的单体来完成。实现了缩短响应时间 通过将该膜配制成一层非常薄的粘合到 另一种高度多孔性的膜也将被执行。中国政府的回应 优化后的膜对葡萄糖的反应将在接触后进行 血液和软组织。组织对优化膜的响应 将对皮下和腹膜内植入进行评估。一秒钟 使用优化葡萄糖的代用植入型递送装置 敏感膜将被开发出来，并通过在小鼠身上植入进行测试。

The further development of glucose sensitive membranes to control insulin delivery at rates which vary with glucose concentration is the goal of the proposed research. The original concept of producing polymers which swell in response to elevated glucose concentrations and allow greater transport of insulin from a reservoir has been demonstrated. The utility of these membranes under conditions approximating their eventual use in an insulin delivery device will be determined in the proposed studies. The aims of the new investigations are to measure insulin transport through glucose sensitive membranes of the present as well as improved design under conditions which test the ability of the membranes to control insulin delivery in a physiologically useful way. Specifically, the following parameters will be measured: insulin permeation rates in the absence of glucose and in the presence of a series of constant, physio-logically-relevant glucose concentrations; the kinetics of changes in permeability induced by controlled increases and decreases in glucose level; the reproducibility of the glucose response; and finally, the long-term stability of the membrane's capability for glucose response. Insulin transport studies will be performed with iodide free 125I insulin prepared with a new procedure developed in our lab and verified with an independent method (immunoassay or colorimetrically). A specially designed transport cell permitting glucose solutions to be pumped through the downstream compartment will be used. The radiation induced polymerization of frozen monomer solutions used successfully to date will continue to be used for membrane preparation. The optimization of the insulin transport properties of the present glucose sensitive membranes will be carried out by designing, preparing and characterizing new membranes formulated with differing ratios of each of the chemical constituents of the membranes. Preparation of membranes with improved swelling and mechanical properties will be done with new monomers. The achievement of improved response time by formulation of the membrane as a very thin "skin" membrane bonded to another, highly porous membrane will also be performed. The response of the optimized membranes to glucose will be evaluated after contact with blood and with soft tissue. The tissue response to the optimized membranes implanted subcutaneously and intraperitoneally will be evaluated. A second generation implantable delivery device employing optimized glucose sensitive membranes will be developed and tested by implantation in mice.