Electroporation and transcutaneous sampling (ETS) of acyclovir.
Electroporation and transcutaneous sampling (ETS) of acyclovir.
复制标题
阿昔洛韦的电穿孔和经皮取样（ETS）。
DOI：
10.1016/j.jdermsci.2007.08.010
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发表时间：
2008
影响因子：
4.6
通讯作者：
Zhang,Shuangqing
中科院分区：
文献类型：
--
作者：
Murthy,SNarasimha;Zhang,Shuangqing
Dermatokinetics determine the efficacy and toxicity of drugs used to treat skin disorders. The time course of drug in the dermal extracellular fluid (ECF) could be used as a tool for assessing the concentration dependent activity/toxicity of the drugs in the skin tissue. Currently dermatokinetic studies of drugs are carried out by tissue biopsy or skin blister sampling or by microdialysis. However, all these methods are invasive and causes significant discomfort to the patients. Microdialysis technique has been used for determination glucose concentration (1, 2), percutaneous absorption (3) of drugs and histamine release in the cutaneous tissue (4). Microdialysis has the advantage of sampling only the free drug (5, 6). ETS is a noninvasive method of reversible permeabilization of stratum corneum and sampling of drugs from the ECF by diffusion. The diffusion flux of drug is governed by the unbound drug concentration gradient between the dermal tissue fluid and the sampling medium. Similar to microdialysis, the ETS samples are from the interstitial space, which is a defined, anatomical compartment and there is no net loss of body fluid (7). The hypothesis is that the transcutaneous flux of drugs is proportional to the concentration of unbound drug in the dermal ECF. Knowing the “reciprocal of Permeability coefficient (1/Pin vivo)” of skin, the unbound drug concentration in the dermal ECF could be determined. The objective of this project was to assess the feasibility of using ETS technique for studying dermatokinetics of acyclovir. Acyclovir, an antiviral agent used in the treatment of herpes simplex infection that occurs at the lowest epidermis. The time course of acyclovir in the dermal ECF is critical in determining the efficacy of acyclovir therapy of herpes simplex. In the present work, Acyclovir was administered to hairless rats and the time course of drug concentration in the dermal ECF was determined by ETS and microdialysis sampling.The experiment was carried out in hairless rats (⁓ 300 g) under ketamine (80 mg/kg) and xylazine (20 mg/kg) anesthesia. For ETS sampling, the shaved portion of the back skin was folded and clamped on to a custom made in vivo electroporation cell. The cell contains a sample collection chamber with platinum wire electrode. A stainless steel plate clamped across the skin fold served as the counter electrode (7, 8). The collection chamber was filled with 200 μl of 0.05% w/v SDS solution prepared in phosphate buffered saline (PBS, pH 7.1) and 15 pulses each of 1 ms duration at 120 V and 1 Hz were applied. The SDS solution in the collection chamber was immediately replaced with 500 μl of PBS, which remained in the collection
