GLUCOSE SENSITIVE MEMBRANES IN THE DELIVERY OF INSULIN

葡萄糖敏感膜调控胰岛素的研究进展 以随葡萄糖浓度变化的速率递送是本发明的目标， 提议的研究。 生产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转运 已经证明了从储药器中释放胰岛素。 这些的效用 膜在接近其最终用于胰岛素的条件下， 将在拟定研究中确定输送器械。 的目的 新的研究是测量胰岛素通过葡萄糖的转运 本发明的敏感膜以及根据本发明的改进设计， 测试膜控制胰岛素的能力的条件 以生理上有用的方式递送。 具体而言， 将测量以下参数：在不存在胰岛素的情况下的胰岛素渗透率 葡萄糖和在一系列恒定的存在下， 生理相关葡萄糖浓度;变化动力学 在由葡萄糖的受控增加和减少诱导的渗透性中， 水平;葡萄糖响应的再现性;最后， 膜对葡萄糖反应能力的长期稳定性。 将使用无碘125 I胰岛素进行胰岛素转运研究 准备在我们的实验室开发的新程序，并验证了 独立方法（免疫测定法或比色法）。 专门设计的 允许葡萄糖溶液被泵送通过 将使用下游隔室。 辐射引发聚合 迄今为止成功使用的冷冻单体溶液将继续 用于制膜。 胰岛素转运的优化 本发明的葡萄糖敏感膜的性质将进行 通过设计、制备和表征新的膜， 膜的每种化学成分的不同比例。 具有改进的溶胀和机械性能的膜的制备 将用新的单体完成。 改进响应时间 通过将膜配制成非常薄的“皮肤”膜 还将形成另一高度多孔的膜。 的响应 将在与以下物质接触后评价对葡萄糖优化的膜： 血液和软组织 组织对优化膜的反应 将对皮下和腹膜内植入的细胞进行评价。 第二 使用优化葡萄糖的第二代可植入递送装置 将开发敏感膜并通过植入小鼠进行测试。

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.