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药物在人体皮肤中侧向扩散的定性和定量分析。

Qualitative and quantitative analysis of lateral diffusion of drugs in human skin.

机构信息

Department of Pharmaceutical Sciences, College of Pharmacy, Mercer University, Atlanta, GA 30341, United States.

Department of Pharmaceutical Sciences, College of Pharmacy, Mercer University, Atlanta, GA 30341, United States.

出版信息

Int J Pharm. 2018 Jun 10;544(1):62-74. doi: 10.1016/j.ijpharm.2018.04.013. Epub 2018 Apr 11.

Abstract

This study aimed to qualitatively and quantitatively analyze lateral diffusion of drugs in dermatomed human skin. Lateral diffusion of calcein and methylene blue dyes in skin was investigated using confocal laser microscopy, calcein imaging, and histology studies. In in vitro permeation studies, two linear microdialysis probes were inserted into the dermis of untreated, poly lacto-glycolic acid microneedle-treated, and ablative laser-treated skin such that one was in the center of the diffusion area and the other was parallel, at 8 mm from the central probe. Skin was mounted on Franz cells, sandwiched between donor containing diclofenac sodium solution and receptor containing phosphate buffered saline, pH 7.4. Qualitative techniques revealed faster lateral diffusion of the dyes in microneedle-treated skin than laser-treated skin. Rate of drug diffusion in the central probe in the microneedle-treated skin (11.8 ± 2.5 μg/h) was significantly higher than untreated and laser-treated skin (p  <  0.05). Rate of lateral diffusion in untreated group (0.7 ± 0.1 μg/h) was significantly lower than microneedle and laser-treated skin (p  <  0.05). Overall, in vitro microdialysis was demonstrated as a novel and valuable tool that can be employed for quantitative investigation of rate of vertical and lateral diffusion of drugs in intact and microporated skin.

摘要

本研究旨在定性和定量分析角质层人体皮肤中药物的侧向扩散。使用共聚焦激光显微镜、钙黄绿素成像和组织学研究研究了钙黄绿素和亚甲蓝染料在皮肤中的侧向扩散。在体外渗透研究中,将两个线性微透析探针插入未经处理、聚乳酸-羟基乙酸微针处理和烧蚀激光处理的皮肤的真皮中,使得一个探针位于扩散区域的中心,另一个探针与中心探针平行,距离为 8mm。将皮肤安装在 Franz 细胞上,将其夹在含有双氯芬酸钠溶液的供体和含有磷酸盐缓冲盐水(pH 7.4)的受体之间。定性技术表明,染料在微针处理的皮肤中的侧向扩散速度快于激光处理的皮肤。在微针处理的皮肤中,中央探针中药物扩散的速度(11.8±2.5μg/h)明显高于未处理和激光处理的皮肤(p<0.05)。未处理组的侧向扩散速度(0.7±0.1μg/h)明显低于微针和激光处理的皮肤(p<0.05)。总之,体外微透析被证明是一种新颖而有价值的工具,可用于定量研究完整和微孔化皮肤中药物垂直和侧向扩散的速率。

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