Zewert T E, Pliquett U F, Vanbever R, Langer R, Weaver J C
Harvard-M.I.T. Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge 02139, USA.
Bioelectrochem Bioenerg. 1999 Oct;49(1):11-20. doi: 10.1016/s0302-4598(99)00056-2.
A combined electrical (HV, "high voltage", pulsing) and chemical (topical sodium thiosulfate) intervention is hypothesized to create enlarged aqueous pathways that allow large quantities of macromolecules to be transported through human skin's stratum corneum (SC), the dominant barrier for transdermal drug delivery and biochemical analyte extraction. This expectation is based on the known structure and composition of the SC, and previous models and experiments for local transport regions (LTRs) due to transdermal HV pulsing. In vitro experiments demonstrated that transdermal macromolecule fluxes of 10(-9) to 10(-8) mol h(-1) cm(-2) (10 to 100 microg h(-1) cm(-2)) or greater are possible for lactalbumin and an antibody (IgG), which are potentially therapeutic values for peptides, proteins and nucleic acids. In the absence of sodium thiosulfate, only a small molecule (sulforhodamine) flux increased significantly, consistent with many previous studies. Significant macromolecule transdermal fluxes occurred only if a pathway enlarging molecule (sodium thiosulfate) was present. Our results also provide support for the mechanism hypothesis that HV pulses leading to transdermal voltages U(skin) > 50 V create straight-through aqueous pathways that penetrate multilamellar bilayer membranes, corneocyte envelopes and corneocyte interiors within the SC.
一种联合的电（高压，“HV”，脉冲）和化学（局部硫代硫酸钠）干预被假定可形成扩大的水性通道，从而允许大量大分子穿过人类皮肤的角质层（SC），角质层是经皮给药和生化分析物提取的主要屏障。这一预期基于角质层已知的结构和组成，以及先前关于经皮高压脉冲引起的局部转运区域（LTRs）的模型和实验。体外实验表明，对于乳白蛋白和一种抗体（IgG），经皮大分子通量达到10(-9)至10(-8) mol h(-1) cm(-2)（10至100 μg h(-1) cm(-2)）或更高是可能的，这些对于肽、蛋白质和核酸具有潜在的治疗价值。在没有硫代硫酸钠的情况下，只有小分子（磺基罗丹明）通量显著增加，这与许多先前的研究一致。只有当存在一种可扩大通道的分子（硫代硫酸钠）时，才会出现显著的大分子经皮通量。我们的结果也为以下机制假说提供了支持，即导致经皮电压U(skin) > 50 V的高压脉冲会形成直接的水性通道，这些通道可穿透角质层内的多层双分子层膜、角质形成细胞包膜和角质形成细胞内部。
