MALDI imaging facilitates new topical drug development process by determining quantitative skin distribution profiles
MALDI imaging facilitates new topical drug development process by determining quantitative skin distribution profiles
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DOI：
10.1007/s00216-018-0964-3
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发表时间：
2018-04-01
影响因子：
4.3
通讯作者：
Nielsen, Kim T.
中科院分区：
文献类型：
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作者：
Bonnel, David;Legouffe, Raphael;Nielsen, Kim T.
在用于治疗皮肤疾病（如牛皮癣和特应性皮炎）的局部产品的开发过程中，皮肤分布曲线的产生和靶区域中药物分子浓度的可靠测定是至关重要的。像质谱成像（MSI）这样的成像技术提供足够的空间分辨率来生成药物分子在皮肤切片上的有意义的分布曲线。在这项研究中，我们使用基质辅助激光解吸/电离质谱成像（MALDI-MSI），以产生定量的皮肤分布曲线的基础上的组织消光系数（TEC）测定四种不同的分子在人体皮肤外植体的横截面局部给药后。四种药物分子：罗氟司特、托法替尼、鲁索利替尼和LEO 29102具有不同的物理化学性质。此外，托法替尼以两种不同制剂给药。该研究表明，使用MALDI-MSI，我们能够观察到四种药物分子和两种制剂的渗透特征的差异，从而证明其在开发局部药物产品时作为筛选工具的适用性。此外，该研究表明，MALDI-MSI技术的灵敏度似乎与药物分子结合周围组织的能力呈负相关，这可以通过其Log D值来估计。
Generation of skin distribution profiles and reliable determination of drug molecule concentration in the target region are crucial during the development process of topical products for treatment of skin diseases like psoriasis and atopic dermatitis. Imaging techniques like mass spectrometric imaging (MSI) offer sufficient spatial resolution to generate meaningful distribution profiles of a drug molecule across a skin section. In this study, we use matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to generate quantitative skin distribution profiles based on tissue extinction coefficient (TEC) determinations of four different molecules in cross sections of human skin explants after topical administration. The four drug molecules: roflumilast, tofacitinib, ruxolitinib, and LEO 29102 have different physicochemical properties. In addition, tofacitinib was administrated in two different formulations. The study reveals that with MALDI-MSI, we were able to observe differences in penetration profiles for both the four drug molecules and the two formulations and thereby demonstrate its applicability as a screening tool when developing a topical drug product. Furthermore, the study reveals that the sensitivity of the MALDI-MSI techniques appears to be inversely correlated to the drug molecules' ability to bind to the surrounding tissues, which can be estimated by their Log D values.