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Mechanisms of ultrasound-microbubble cavitation for inducing the permeability of human skin
Journal of Controlled Release ( IF 10.5 ) Pub Date : 2022-07-14 , DOI: 10.1016/j.jconrel.2022.06.056
Ai-Ho Liao , Yu-Chen Chen , Chia-Yu Chen , Shun-Cheng Chang , Ho-Chiao Chuang , Dao-Lung Lin , Chien-Ping Chiang , Chih-Hung Wang , Jehng-Kang Wang

We have previously reported that ultrasound (US)-mediated microbubble (MB) cavitation (US-MB) changed the permeability of the skin and significantly enhanced transdermal drug delivery (TDD) without changing the structure of the skin. In this study we found that US-MB enhanced TDD via disruption of epidermal cell–cell junctions and increased matriptase activity. Matriptase is a membrane-bound serine protease regulated by its inhibitor hepatocyte growth factor activator inhibitor-1 (HAI-1), and it is expressed in most epithelial tissues under physiologic conditions. Matriptase is expressed in mice after chronic exposure to UV radiation. This study found that US-MB can be used to monitor active matriptase, which rapidly formed the canonical 120-kDa matriptase–HAI-1 complex. These processes were observed in HaCaT human keratinocytes when matriptase activation was induced by US-MB. The results of immunoblot analysis indicated that the matriptase–HAI-1 complex can be detected from 10 min to 3 h after US-MB. Immunohistochemistry (IHC) of human skin revealed that US-MB rapidly increased the activated matriptase, which was observed in the basal layer, with this elevation lasting 3 h. After 3 h, the activated matriptase extended from the basal layer to the granular layer, and then gradually decayed from 6 to 12 h. Moreover, prostasin expression was observed in the epidermal granular layer to the spinous layer, and became more obvious in the granular layer after 3 h. Prostasin was also detected in the cytoplasm or on the cell membrane after 6 h. These results suggest that matriptase plays an important role in recovering from US-MB-induced epidermal cell–cell junction disruption within 6 h. US-MB is therefore a potentially effective method for noninvasive TDD in humans.



中文翻译:

超声-微泡空化诱导人体皮肤渗透的机制

我们之前曾报道过超声 (US) 介导的微泡 (MB) 空化 (US-MB) 改变了皮肤的渗透性并显着增强了透皮给药 (TDD) 而不会改变皮肤的结构。在这项研究中,我们发现 US-MB通过表皮细胞 - 细胞连接的破坏和增加的matriptase活性。Matriptase 是一种膜结合丝氨酸蛋白酶,受其抑制剂肝细胞生长因子激活剂抑制剂-1 (HAI-1) 的调节,在生理条件下在大多数上皮组织中表达。在长期暴露于紫外线辐射后,Matriptase 在小鼠中表达。这项研究发现,US-MB 可用于监测活性基质酶,它迅速形成典型的 120-kDa 基质酶-HAI-1 复合物。当 US-MB 诱导 matriptase 激活时,在 HaCaT 人角质形成细胞中观察到这些过程。免疫印迹分析结果表明,matriptase-HAI-1 复合物可以在 US-MB 后 10 分钟到 3 小时内被检测到。人体皮肤的免疫组织化学 (IHC) 显示 US-MB 迅速增加了活化的基质酶,在基底层观察到,这种抬升持续了 3 小时。3 h后,活化的matriptase从基底层延伸至颗粒层,6~12 h逐渐衰减。表皮颗粒层至棘层均有前列腺素表达,3 h后颗粒层表达更为明显。6小时后还在细胞质或细胞膜上检测到前列腺素。这些结果表明,matriptase 在 6 小时内从 US-MB 诱导的表皮细胞 - 细胞连接破坏中恢复中起重要作用。因此,US-MB 是人类非侵入性 TDD 的潜在有效方法。表皮颗粒层至棘层可见前列腺素表达,3 h后颗粒层表达更为明显。6小时后还在细胞质或细胞膜上检测到前列腺素。这些结果表明,matriptase 在 6 小时内从 US-MB 诱导的表皮细胞 - 细胞连接破坏中恢复中起重要作用。因此,US-MB 是人类非侵入性 TDD 的潜在有效方法。表皮颗粒层至棘层可见前列腺素表达,3 h后颗粒层表达更为明显。6小时后还在细胞质或细胞膜上检测到前列腺素。这些结果表明,matriptase 在 6 小时内从 US-MB 诱导的表皮细胞 - 细胞连接破坏中恢复中起重要作用。因此,US-MB 是人类非侵入性 TDD 的潜在有效方法。

更新日期:2022-07-14
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