Visualisation of drug distribution in skin using correlative optical spectroscopy and mass spectrometry imaging.
Visualisation of drug distribution in skin using correlative optical spectroscopy and mass spectrometry imaging.
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使用相关光谱和质谱成像可视化皮肤中的药物分布。
DOI：
10.1016/j.jconrel.2023.10.026
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Bettex,
中科院分区：
文献类型：
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作者：
Belsey,NatalieA;Dexter,Alex;Vorng,Jean-Luc;Tsikritsis,Dimitrios;Nikula,ChelseaJ;Murta,Teresa;Tiddia,Maria-Vitalia;Zhang,Junting;Gurdak,Elzbieta;Trindade,GustavoF;Gilmore,IanS;Page,Leanne;Roper,CliveS;Guy,RichardH;Bettex,
已经开发了一种用于软组织的无标记化学成像的相关方法，将非线性光学光谱学和质谱学相结合，以实现亚微米空间分辨率和大幅提高的药物检测灵敏度。该方法被应用于可视化的动力学药物储库形成后，在体外局部治疗与商业双氯芬酸凝胶在人体皮肤内。非破坏性的光学光谱技术，即受激拉曼散射，二次谐波产生和双光子荧光显微镜，被用来提供化学和结构的对比。随后通过二次离子质谱法对相同的组织切片进行分析，该方法对整个表皮和真皮中的双氯芬酸检测具有更高的灵敏度。开发了一种使用图像配准技术将光学和质谱数据集联合收割机组合的方法。组织结构的无标记、高分辨率可视化加上灵敏的化学检测为皮肤中的药物生物分布研究提供了一种强有力的方法，直接影响局部药物产品的开发。
A correlative methodology for label-free chemical imaging of soft tissue has been developed, combining non-linear optical spectroscopies and mass spectrometry to achieve sub-micron spatial resolution and critically improved drug detection sensitivity. The approach was applied to visualise the kinetics of drug reservoir formation within human skin following in vitro topical treatment with a commercial diclofenac gel. Non-destructive optical spectroscopic techniques, namely stimulated Raman scattering, second harmonic generation and two photon fluorescence microscopies, were used to provide chemical and structural contrast. The same tissue sections were subsequently analysed by secondary ion mass spectrometry, which offered higher sensitivity for diclofenac detection throughout the epidermis and dermis. A method was developed to combine the optical and mass spectrometric datasets using image registration techniques. The label-free, high-resolution visualisation of tissue structure coupled with sensitive chemical detection offers a powerful method for drug biodistribution studies in the skin that impact directly on topical pharmaceutical product development.