The application of local hypobaric pressure - A novel means to enhance macromolecule entry into the skin.
The application of local hypobaric pressure - A novel means to enhance macromolecule entry into the skin.
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DOI：
10.1016/j.jconrel.2016.01.052
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发表时间：
2016-03-28
期刊：
影响因子：
--
通讯作者：
Jones SA
中科院分区：
文献类型：
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作者：
Inacio R;Poland S;Cai XJ;Cleary SJ;Ameer-Beg S;Keeble J;Jones SA
局部施加可控的减压压力代表了一种促进药物进入皮肤的新方法。这项工作的目的是了解减压压力如何改变皮肤的性质，并评估这种渗透促进策略是否可以改善大分子的经皮渗透。皮肤厚度的测量表明，局部施加减压使组织变薄(P<0.001)，原子力显微镜显示它使角质层中的角质细胞缩小(P<0.001)，多光子显微镜对皮肤毛囊的成像显示它打开了毛囊漏斗(P<0.001)。总而言之，这些变化导致10,000分子的葡聚糖分子在体外经皮渗透增加了19.6倍，使用荧光显微镜显示，当使用减压压力施加到皮肤上时，这种分子定位于毛囊周围。在体内，在大鼠体内，局部血流动力学反应(即血流量显著增加，P<0.001)有助于增加葡聚糖的毛囊转运，产生7.2%±2.81FG·mL−=1的全身吸收。当未对大鼠施加减压应激时，没有检测到葡聚糖的吸收，这为这种新的渗透促进技术提供了证据，表明这种新的渗透促进技术可以改善局部皮肤应用后大分子的经皮渗透。
The local application of controlled hypobaric stress represents a novel means to facilitate drug delivery into the skin. The aims of this work were to understand how hypobaric stress modified the properties of the skin and assess if this penetration enhancement strategy could improve the percutaneous penetration of a macromolecule. Measurements of skin thickness demonstrated that the topical application of hypobaric stress thinned the tissue (p < 0.05), atomic force microscopy showed that it shrunk the corneocytes in the stratum corneum (p < 0.001) and the imaging of the skin hair follicles using multiphoton microscopy showed that it opened the follicular infundibula (p < 0.001). Together, these changes contributed to a 19.6-fold increase in in vitro percutaneous penetration of a 10,000 molecular weight dextran molecule, which was shown using fluorescence microscopy to be localized around the hair follicles, when applied to the skin using hypobaric stress. In vivo, in the rat, a local hemodynamic response (i.e. a significant increase in blood flow, p < 0.001) was shown to contribute to the increase in follicular transport of the dextran to produce a systemic absorption of 7.2 ± 2.81 fg·mL− 1. When hypobaric stress was not applied to the rat there was no detectable absorption of dextran and this provided evidence that this novel penetration enhancement technique can improve the percutaneous penetration of macromolecules after topical application to the skin.