驻极体产生的静电场与胰岛素的相互作用及其药效学初探

Interaction Between Electrostatic Field Generated by Electret with Insulin and Its Pharmacodynamics Exploration

为了研究驻极体对胰岛素溶液中胰岛素的渗透性和聚集态的影响,利用高压真空镀膜法制备了单电极聚丙烯驻极体,借助常温栅控恒压电晕充电法制备了不同初始表面电位、不同极性的单电极和双裸面驻极体。通过等效表面电位衰减测量和蛋白质电泳技术检测了驻极体透过胰岛素溶液后的等效表面电位衰减规律和驻极体对胰岛素聚集态的影响,并利用糖尿病大鼠模型进行了初步的胰岛素药效学研究。研究结果表明:经过驻极体连续作用48 h后,不同极性和初始表面电位的单电极驻极体透过胰岛素溶液后的等效表面电位衰减量均低于相应的双裸面驻极体组,其中±1 000 V单电极驻极体表现出更优异的电荷储存稳定性;经过驻极体连续作用24 h,胰岛素电泳分析结果显示胰岛素溶液的聚集态并未发生改变,均以单聚体和二聚体为主;-1 000 V驻极体作用后的胰岛素降糖效果显著。可得以下结论:±1 000 V驻极体透过胰岛素溶液后其电荷储存能力较优;驻极体的作用并不改变胰岛素自身的结构;驻极体可望用于制备驻极体胰岛素透皮吸收新剂型,为胰岛素透皮吸收提供了一种新的方便快捷的给药方式。

We experimentally studied the effects of electret on the permeability and the aggregation state of insulin in solution. A single aluminum coated polyprolene（PP） electret was prepared using the high-pressure vacuum coating method, and some dual-bare or single aluminum coated PP electrets with different initial surface potential and electric polarities were prepared using a corona charging system. By means of equivalent surface potential decay measurement and protein electrophoresis test, we evaluated the regularity of the decay and the aggregation state of insulin. Moreover, taking some diabetic rats as the model, we studied the pharmacodynamics of insulin. The results show that, after 48 hours, the surface potential of the single aluminum coated electret penetrates the saturated insulin solution better than that of the dual-bare electret, while the electrets applied with ±1 000 V have the best charge storage stability among the tested samples. The insulin electrophoresis analysis shows that, after being treated by electret for 24 hours continuously, the aggregation of the insulin solution does not change, which is mainly constituted of single dimers and double dimers. The hypoglycemic effect of the insulin solution treated by –1 000 V electret is remarkable. It is clear that the ±1 000 V electrets used in the experiments have excellent charge storage stability, and the electret treatment does not change the insulin structure. Therefore, it is promising for the insulin trans-dermal drug preparation and the transdermal absorption of insulin, which is a novel way of convenient dosing.