Transdermal insulin delivery using lipid enhanced electroporation.
Transdermal insulin delivery using lipid enhanced electroporation.
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使用脂质增强电穿孔进行透皮胰岛素递送。
DOI：
10.1016/s0005-2736(02)00453-4
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Hui,SekWen
中科院分区：
文献类型：
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作者：
Sen,Arindam;Daly,MeganE;Hui,SekWen
利用猪表皮和荧光素标记的胰岛素，电穿孔法测定胰岛素的透皮转运。先前的研究表明，阴离子脂质可以增强10 kDa大小的分子的电穿孔运输。研究还表明，影响电穿孔下的透皮转运的是磷脂头基团的电荷而不是类型。此外，具有饱和酰基链的磷脂比具有不饱和链的磷脂更能促进大分子的运输。在目前的研究中，基于这些早期的发现，1,2-二肉豆醇-3-磷脂酰丝氨酸（DMPS）对胰岛素电穿孔透皮转运的影响进行了研究。以猪表皮为皮肤模型。运输是用玻璃垂直扩散仪测量的，其中表皮将供体和受体隔离开。使用铂电极在表皮上施加负脉冲。结果表明，在DMPS存在的情况下进行电穿孔时，胰岛素的转运能力增加了20倍以上。此外，当磷脂存在时，几乎所有转运的胰岛素都在受体室中被检测到；在没有添加脂质的情况下，只有大约一半的胰岛素被输送到受体室，几乎等量的胰岛素留在表皮。荧光显微镜显示胰岛素转运主要通过角质细胞周围的脂质多层区。
Transdermal insulin transport by electroporation was measured using porcine epidermis and fluorescein-labeled insulin. Previous studies have shown that anionic lipids can enhance the electroporative transport of molecules up to 10 kDa in size. It was also shown that it is the charge and not the type of the phospholipid head group that influences transdermal transport under electroporation. Moreover, phospholipids with saturated acyl chains enhance the transport of larger molecules more as compared to those with unsaturated chains. In the current study, based on those earlier findings, the effect of 1,2-dimyristoyl-3-phosphatidylserine (DMPS) on the transdermal transport of insulin by electroporation was examined. Porcine epidermis was used as a model for skin. Transport was measured using glass vertical diffusion apparatus in which the epidermis separated the donor and receiver compartments. Negative pulses were applied across the epidermis using platinum electrodes. Results show that when electroporation was carried out in the presence of DMPS, there was greater than 20-fold enhancement of insulin transport. Furthermore, while in the presence of the phospholipid, almost all the transported insulin was detected in the receiver compartment; in the absence of added lipids, only about half the insulin transported was in the receiver compartment and an almost equal amount of insulin remained in the epidermis. Fluorescence microscopy revealed that the insulin transport was mainly through the lipid multilayer regions that surround the corneocytes.