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微针长度、密度、插入时间和多次应用对人体皮肤屏障功能的影响:经皮水分流失评估。

Effects of microneedle length, density, insertion time and multiple applications on human skin barrier function: assessments by transepidermal water loss.

机构信息

SIPBS, University of Strathclyde, 27 Taylor Street, Glasgow, G4 0NR, Scotland, UK.

出版信息

Toxicol In Vitro. 2010 Oct;24(7):1971-8. doi: 10.1016/j.tiv.2010.08.012. Epub 2010 Aug 21.

Abstract

Microneedle (MN) arrays have attracted considerable attention in recent years due to their ability to facilitate effective transdermal drug delivery. Despite appreciable research, there is still debate about how different MN dimensions or application modes influence permeabilization. This study aimed to investigate this issue by taking transepidermal water-loss measurements of dermatomed human skin samples following the insertion of solid polymeric MNs. Insertions caused an initial sharp drop in barrier function followed by a slower incomplete recovery - a paradigm consistent with MN-generation of microchannels that subsequently contract due to skin elasticity. While 600 μm-long MNs were more skin-perturbing than 400 μm MNs, insertion of 1000 μm-long MNs caused a smaller initial drop in integrity followed by a degree of long term permeabilization. This is explainable by the longest needles compacting the tissue, which then decompresses over subsequent hours. Multiple insertions had a similar effect as increasing MN length. There was some evidence that increasing MN density suppressed the partial barrier recovery caused by tissue contraction. Leaving MNs embedded in skin seemed to reduce the initial post-insertion drop in barrier function. Our results suggest that this in vitro TEWL approach can be used to rapidly screen MN-effects on skin.

摘要

微针 (MN) 阵列近年来受到了相当多的关注,因为它们能够促进有效的经皮药物传递。尽管已经进行了大量的研究,但关于不同的 MN 尺寸或应用模式如何影响通透性仍然存在争议。本研究旨在通过测量角质层分离的人体皮肤样本在插入固体聚合物 MN 后的经表皮水分损失来研究这个问题。插入会导致屏障功能的初始急剧下降,随后是较慢且不完全的恢复 - 这一现象与 MN 产生微通道的现象一致,微通道随后由于皮肤弹性而收缩。虽然 600 μm 长的 MN 比 400 μm MN 对皮肤的干扰更大,但插入 1000 μm 长的 MN 会导致初始完整性下降较小,随后出现一定程度的长期通透性。这可以用最长的针压缩组织来解释,然后在随后的几个小时内组织会解压。多次插入的效果与增加 MN 长度的效果相似。有一些证据表明,增加 MN 的密度可以抑制组织收缩引起的部分屏障恢复。将 MN 留在皮肤中似乎可以减少插入后初始阶段的屏障功能下降。我们的结果表明,这种体外 TEWL 方法可用于快速筛选 MN 对皮肤的影响。

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