Kushner Joseph, Kim Daekeun, So Peter T C, Blankschtein Daniel, Langer Robert S
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
J Invest Dermatol. 2007 Dec;127(12):2832-46. doi: 10.1038/sj.jid.5700908. Epub 2007 Jun 7.
Visualization of transdermal permeant pathways is necessary to substantiate model-based conclusions drawn using permeability data. The aim of this investigation was to visualize the transdermal delivery of sulforhodamine B (SRB), a fluorescent hydrophilic permeant, and of rhodamine B hexyl ester (RBHE), a fluorescent hydrophobic permeant, using dual-channel two-photon microscopy (TPM) to better understand the transport pathways and the mechanisms of enhancement in skin treated with low-frequency ultrasound (US) and/or a chemical enhancer (sodium lauryl sulfate--SLS) relative to untreated skin (the control). The results demonstrate that (1) both SRB and RBHE penetrate beyond the stratum corneum and into the viable epidermis only in discrete regions (localized transport regions--LTRs) of US treated and of US/SLS-treated skin, (2) a chemical enhancer is required in the coupling medium during US treatment to obtain two significant levels of increased penetration of SRB and RBHE in US-treated skin relative to untreated skin, and (3) transcellular pathways are present in the LTRs of US treated and of US/SLS-treated skin for SRB and RBHE, and in SLS-treated skin for SRB. In summary, the skin is greatly perturbed in the LTRs of US treated and US/SLS-treated skin with chemical enhancers playing a significant role in US-mediated transdermal drug delivery.
可视化透皮渗透途径对于证实基于渗透率数据得出的模型结论是必要的。本研究的目的是使用双通道双光子显微镜（TPM）可视化磺基罗丹明B（SRB，一种荧光亲水性渗透剂）和罗丹明B己酯（RBHE，一种荧光疏水性渗透剂）的透皮递送，以更好地了解相对于未处理皮肤（对照），在低频超声（US）和/或化学增强剂（十二烷基硫酸钠 - SLS）处理的皮肤中的转运途径和增强机制。结果表明：（1）仅在US处理和US/SLS处理皮肤的离散区域（局部转运区域 - LTRs）中，SRB和RBHE才穿透角质层并进入有活力的表皮；（2）在US处理期间，耦合介质中需要化学增强剂，以获得相对于未处理皮肤，SRB和RBHE在US处理皮肤中显著增加的两个渗透水平；（3）对于SRB和RBHE，在US处理和US/SLS处理皮肤的LTRs中存在跨细胞途径，对于SRB，在SLS处理的皮肤中也存在跨细胞途径。总之，在US处理和US/SLS处理皮肤的LTRs中，皮肤受到极大干扰，化学增强剂在US介导的透皮给药中起重要作用。
