Volpato N M, Nicoli S, Laureri C, Colombo P, Santi P
Pharmaceutical Department, University of Parma, Italy.
J Control Release. 1998 Jan 2;50(1-3):291-6. doi: 10.1016/s0168-3659(97)00152-1.
The purpose of the present work was to study the in vitro distribution of acyclovir in human skin layers after iontophoresis, applied in order to increase the amount of drug in the basal epidermis, site of Herpes simplex infections. Experiments were done with Franz diffusion cells applying, as donor, acyclovir solutions (pH values: 3.0 and 7.4) or a commercial cream. Quantification of drug at different skin depths was performed by horizontal slicing of frozen skin, and drug extraction and analysis by high-performance liquid chromatography. Seven h of transdermal iontophoresis (0.5 mA cm-2 induced an accumulation of acyclovir in epidermis and dermis ranging from 80 to 150 micrograms cm-3, characterized by homogeneous distribution of the drug in skin layers. After short current application time (30 min) however, the concentration profile of drug in skin was not significantly different from the obtained after seven h of passive diffusion, employing pH 3.0 donor solution. After 30 min of iontophoresis, the acyclovir reservoir on the skin was maintained for up to five h producing a dramatic increase of drug concentration in skin, evening out over 80 micrograms cm-3 until a depth of 300 micrograms. Acyclovir can be accumulated at target site more quickly and maintained at higher level through application of a iontophoretic pulse and by keeping the drug reservoir on skin.
本研究的目的是研究离子电渗疗法后阿昔洛韦在人体皮肤各层中的体外分布情况，离子电渗疗法用于增加单纯疱疹感染部位——基底表皮中的药物含量。实验使用Franz扩散池，以阿昔洛韦溶液（pH值：3.0和7.4）或市售乳膏作为供体。通过对冷冻皮肤进行水平切片来定量不同皮肤深度的药物，并通过高效液相色谱法进行药物提取和分析。7小时的经皮离子电渗疗法（0.5 mA cm-2）使阿昔洛韦在表皮和真皮中的蓄积量达到80至150微克/立方厘米，其特征是药物在皮肤各层中分布均匀。然而，在短时间施加电流（30分钟）后，使用pH 3.0供体溶液时，皮肤中药物的浓度分布与被动扩散7小时后获得的浓度分布没有显著差异。离子电渗疗法30分钟后，皮肤表面的阿昔洛韦储库可维持长达5小时，导致皮肤中药物浓度急剧增加，在深度达300微克处均匀达到80微克/立方厘米以上。通过施加离子电渗脉冲并将药物储库保留在皮肤上，阿昔洛韦可以更快地在靶部位蓄积并维持在较高水平。
