Synergistic effect of electric field and ultrasound on transdermal transport

Synergistic effect of electric field and ultrasound on transdermal transport
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DOI:
10.1023/a:1016070710397
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发表时间:
1996-04-01
影响因子:
3.7
通讯作者:
Weaver, J
Weaver, J
中科院分区:
医学3区
文献类型:
--
作者:
Kost, J;Pliquett, U;Weaver, J

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经皮给药为口服给药和注射给药提供了一种替代方法(1)。然而,由于皮肤最外层--粉刺层(SC)的低渗透性,目前其应用仅限于少数药物。SC由死细胞(角质形成细胞)处的fl组成,其高度有序的结构使SC具有不通透性。化学促进剂(2)、超声(3-4)和电促进(5-8)等方法已被提出用于促进药物的透皮吸收。在某些情况下,需要高强度的物理化学力(例如,电、超声波)才能将给定剂量的药物经皮传递。然而,可以使用的这些物理化学力的最高强度可能会受到它们不利的生理影响的限制。同时施加一种以上的物理化学力可能会降低实现特定经皮转运增强所需的这些力的强度。电穿孔包括施加电场脉冲,在脂质双层膜上产生瞬时的水通道,导致皮肤结构的暂时改变。虽然水孔的出现可能允许中性分子通过扩散经皮渗透,但带电分子在脉冲过程中的传输主要通过电泳法和电雾法进行(5-7)。另一方面,建议应用超声波来增强皮肤的通透性,这是由于空化导致软骨层脂质双层的解体(4)。此外,还提出了超声透入过程中发生对流输送的可能性。由于超声波和电fi促进透皮吸收的机制不同,我们推测它们的结合可能会产生协同效应。在这篇文章中,我们研究了同时施加超声波和电脉冲引起的透皮吸收增强是否高于电脉冲或
Transdermal drug delivery offers a substitute method to oral drug delivery and injections for drug administration (1). However, its applications are currently limited to only a few drugs due to the low permeability of the stratum comeum (SC), the outermost layer of the skin. The SC consists of flat dead cells (keratinocytes) surrounded by lipid bilayers, whose highly ordered structure confers an impermeable nature to the SC. Various approaches including chemical enhancers (2), ultra-sound (3-4) and electrical enhancement (5-8) have been suggested to enhance transdermal drug transport. In some cases, high strengths of the physico-chemical forces (for example, electricity, ultrasound) are required to deliver a given drug dose transdermally. However, the highest strength of these physicochemical forces that can be used is likely to be limited by their adverse physiological effects. It is possible that simultaneous application of more than one physico-chemical force may decrease the required strength of these forces to achieve a given transderrnal transport enhancement. Electroporation involves application of electric field pulses that create transient aqueous pathways in lipid bilayer membranes, causing a temporary alteration of skin structure. While occurrence of aqueous pores may allow transderrnal permeation of neutral molecules by diffusion, the transport of charged molecules during pulsing occurs predominantly by electrophoresis and electrosmosis (5-7). On the other hand, application of ultrasound has been suggested to enhance skin permeability due to cavitation which induces disorganization of the stratum comeum lipid bilayers (4). In addition, occurrence of convective transport during sonophoresis has also been suggested (3). Because the mechanism by which ultrasound and electric field enhance transdermal transport are different, we hypothesized that their combination might result in a synergistic effect. In this note, we examine whether the transdermal transport enhancement induced by simultaneous application of ultrasound and electric pulses is higher than that due to electric pulses or