Confocal Raman Spectroscopic Characterization of Dermatopharmacokinetics Ex Vivo.
Confocal Raman Spectroscopic Characterization of Dermatopharmacokinetics Ex Vivo.
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体外皮肤药代动力学的共聚焦拉曼光谱表征
DOI：
10.1021/acs.molpharmaceut.3c00755
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发表时间：
2023-11-06
影响因子：
4.9
通讯作者：
Guy RH
中科院分区：
文献类型：
--
作者：
Zarmpi P;Tabosa MAM;Vitry P;Bunge AL;Belsey NA;Tsikritsis D;Woodman TJ;Delgado-Charro MB;Guy RH
共焦拉曼光谱正在被评估为一种工具，可用于量化皮肤角质层 (SC) 屏障下方的活表皮内的药物吸收和清除目标作用位点的速率和程度。本研究的目的是确认拉曼可以询问皮肤活层内的药物分布（许多外用药物在皮肤中产生药理作用），并确定可以校正和标准化拉曼信号随皮肤深度增加而衰减的程序，以便可以确定描述局部生物利用度的指标。在平行于皮肤表面的皮肤横截面的实验中首次表明，主要源自角蛋白的酰胺 I 信号随着皮肤深度的变化而相当恒定，并且可以用于校正以“自上而下”方式获取共焦拉曼数据时的信号衰减。然后，使用具有强拉曼活性 C=N 功能的 4-氰基苯酚 (CP) 作为模型皮肤渗透剂，进行了一系列随时间变化的吸收和清除实验，清楚地证明标准化光谱数据能够检测到皮肤中至少 40-80 μm 的渗透剂，并区分不同载体中 CP 的处置。与局部生物利用度（和潜在的生物等效性）相关的指标包括归一化 CeqN 信号下的面积与深度分布以及制剂去除后推导出的消除率常数。最后，使用经批准的皮肤病药物 crisaborole 进行拉曼测量，可检测到该药物从完全饱和的制剂输送到 SC 下方的皮肤层。
Confocal Raman spectroscopy is being assessed as a tool with which to quantify the rate and extent of drug uptake to and its clearance from target sites of action within the viable epidermis below the skin’s stratum corneum (SC) barrier. The objective of this research was to confirm that Raman can interrogate drug disposition within the living layers of the skin (where many topical drugs elicit their pharmacological effects) and to identify procedures by which Raman signal attenuation with increasing skin depth may be corrected and normalized so that metrics descriptive of topical bioavailability may be identified. It was first shown in experiments on skin cross-sections parallel to the skin surface that the amide I signal, originating primarily from keratin, was quite constant with depth into the skin and could be used to correct for signal attenuation when confocal Raman data were acquired in a “top-down” fashion. Then, using 4-cyanophenol (CP) as a model skin penetrant with a strong Raman-active C≡N functionality, a series of uptake and clearance experiments, performed as a function of time, demonstrated clearly that normalized spectroscopic data were able to detect the penetrant to at least 40–80 μm into the skin and to distinguish the disposition of CP from different vehicles. Metrics related to local bioavailability (and potentially bioequivalence) included areas under the normalized C≡N signal versus depth profiles and elimination rate constants deduced post-removal of the formulations. Finally, Raman measurements were made with an approved dermatological drug, crisaborole, for which delivery from a fully saturated formulation into the skin layers just below the SC was detectable.
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影响因子：
4.9
作者：
Tabosa, M. Alice Maciel;Vitry, Pauline;Zarmpi, Panagiota;Bunge, Annette L.;Belsey, Natalie A.;Tsikritsis, Dimitrios;Woodman, Timothy J.;White, K. A. Jane;Delgado-Charro, M. Begona;Guy, Richard H.
通讯作者：
Guy, Richard H.
影响因子：
4.9
作者：
Garvie-Cook, Hazel;Hoppel, Magdalena;Guy, Richard H.
通讯作者：
Guy, Richard H.
影响因子：
3.4
作者：
Caspers, PJ;Lucassen, GW;Puppels, GJ
通讯作者：
Puppels, GJ
影响因子：
6.5
作者：
Caspers, PJ;Lucassen, GW;Puppels, GJ
通讯作者：
Puppels, GJ
影响因子：
3.5
作者：
Everall, NJ
通讯作者：
Everall, NJ