Reverse Iontophoresis: Noninvasive Assessment of Topical Drug Bioavailability.
Reverse Iontophoresis: Noninvasive Assessment of Topical Drug Bioavailability.
复制标题
DOI：
10.1021/acs.molpharmaceut.3c00791
复制
发表时间：
2024-01-01
影响因子：
4.9
通讯作者：
Guy, Richard H.
中科院分区：
文献类型：
--
作者：
Moore, Kieran;Gregoire, Sebastien;Eilstein, Joan;Delgado-Charro, M. Begona;Guy, Richard H.
关键词：
在施用局部制剂后评估药物在皮肤中的分布是很困难的。据推测，反向离子电渗疗法（RI）可以提取带电/极性分子用于监测目的，可以为评估局部药物生物利用度提供一种非侵入性方法。在分别使用前者的简单溶液和后者的透皮贴剂 24 小时和 8 小时后，对猪皮肤中水杨酸 (SA) 和尼古丁 (NIC) 的被动提取和 RI 提取进行了评估。在“被动皮肤加载”之后，立即测量角质层（SC）和“活”组织（VT）中的药物量（a）在胶带剥离和随后的两个皮肤层的溶剂提取后或（b）在 RI 提取 4 小时后。然后在健康志愿者体内进行平行实验；在这种情况下，VT 没有被采样，NIC 的皮肤加载时间仅为 4 小时。两种药物的 RI 提取率（体外和体内）均显着高于被动实现的提取率，并且使用简单的隔室模型对作为时间函数的累积 RI 提取曲线进行了数学分析。然后确定“加载”结束时 SC 和 VT 中药物量（分别为 ASC,0 和 AVT,0）的最佳拟合估计值以及描述模型室之间转移的两个一阶速率常数。 ASC,0 和 AVT,0 的体外预测与实验结果非常一致，前者的体内值也是如此。体外和体内结果得出的速率常数也相似。总之，结果提供了概念验证，即 RI 方法有潜力无创评估皮肤中药物生物利用度的相关指标。
Assessing drug disposition in the skin after the application of a topical formulation is difficult. It is hypothesized that reverse iontophoresis (RI), which can extract charged/polar molecules for monitoring purposes, may provide a noninvasive approach for the assessment of local drug bioavailability. The passive and RI extraction of salicylic acid (SA) and nicotine (NIC) from porcine skin in vitro was assessed after a simple solution of the former and a transdermal patch of the latter had been applied for 24 and 8 h, respectively. Immediately after this “passive skin loading”, the amount of drug in the stratum corneum (SC) and “viable” tissue (VT) was measured either (a) after tape-stripping and subsequent solvent extraction of both skin layers or (b) following RI extraction over 4 h. Parallel experiments were then performed in vivo in healthy volunteers; in this case, the VT was not sampled and the skin loading period for NIC was only 4 h. RI extraction of both drugs was significantly higher (in vitro and in vivo) than that achieved passively, and the cumulative RI extraction profiles as a function of time were mathematically analyzed using a straightforward compartmental model. Best-fit estimates of drug amounts in the SC and VT (ASC,0 and AVT,0, respectively) at the end of “loading” and two first-order rate constants describing transfer between the model compartments were then determined. The in vitro predictions of ASC,0 and AVT,0 were in excellent agreement with the experimental results, as was the value of the former in vivo. The rate constants derived from the in vitro and in vivo results were also similar. In summary, the results provide proof-of-concept that the RI method has the potential to noninvasively assess relevant metrics of drug bioavailability in the skin.
登录
查看更多内容
影响因子：
5.8
作者：
Cordery SF;Pensado A;Chiu WS;Shehab MZ;Bunge AL;Delgado-Charro MB;Guy RH
通讯作者：
Guy RH
影响因子：
2.7
作者：
Au, W. L.;Skinner, M. F.;Kanfer, I.
通讯作者：
Kanfer, I.
影响因子：
5.8
作者：
Mateus, R.;Abdalghafor, H.;Lane, M. E.
通讯作者：
Lane, M. E.
影响因子：
1.2
作者：
Cheruvu, Hanumanth Srikanth;Liu, Xin;Grice, Jeffrey E.;Roberts, Michael S.
通讯作者：
Roberts, Michael S.
影响因子：
3.7
作者：
Bodenlenz M;Augustin T;Birngruber T;Tiffner KI;Boulgaropoulos B;Schwingenschuh S;Raney SG;Rantou E;Sinner F
通讯作者：
Sinner F