Abstract
In pharmacokinetic studies of topical drugs, fluorescence microscopy methods can enable the direct visualization and quantification of fluorescent drugs within the skin. One potential limitation of this approach, however, is the strong endogenous fluorescence of skin tissues that makes straightforward identification of specific drug molecules challenging. To study this effect and quantify endogenous skin fluorescence in the context of topical pharmacokinetics, an integrating sphere-based screening tool was designed to collect fluorescence yield data from human skin specimens. Such information could be utilized to select specific donors in the investigation of drug uptake and distribution. Results indicated human facial skin specimens from a group of more than 35 individuals exhibited an at least 6-fold difference in endogenous fluorescence. In visualizing drug distributions, the negative impact of autofluorescence could be exacerbated in cases where there are overlapping spatial distributions or spectral emission profiles between endogenous fluorophores and the exogenous fluorophore of interest. We demonstrated the feasibility of this approach in measuring the range of tissue endogenous fluorescence and selecting specimens for the study of drug pharmacokinetics with fluorescence microscopy.
Highlights
Radiolabeling has been the mainstay for assessing drug distribution within tissue or organs in the pharmaceutical industry, using both quantitative whole-body autoradiography (QWBA) [1,2,3] and microautoradiography (MARG) [4] tools
El-Mashtoly et al [8] demonstrated the use of Raman microscopy in tracking the cellular distribution of label-free erlotinib, a tyrosine kinase inhibitor targeting the epidermal growth factor receptor (EGFR) for cancer treatment [9]
We have recently demonstrated the visualization of minocycline hydrochloride, an antibiotic used in the treatment of acne vulgaris, in excised human facial skin specimens using conventional fluorescence microscopy with concurrent high-performance liquid
Summary
Radiolabeling has been the mainstay for assessing drug distribution within tissue or organs in the pharmaceutical industry, using both quantitative whole-body autoradiography (QWBA) [1,2,3] and microautoradiography (MARG) [4] tools. QWBA is limited in resolving power when submillimeter resolution is required [3], and radiolabeling can potentially change the pharmacokinetics of the drug. Recent advances in mass spectrometry [1,2,3], matrix assisted laser desorption/ionization (MALDI) [3], and variants [5] of mass spectrometric imaging (MSI) have provided two-dimensional mapping of drug distribution with high specificity and resolution without the need to modify the target drug. The potential of nonlinear optical microscopy has recently been explored for the visualization of drug distributions [6,7,8,9]. Thorling et al [7] showed the distribution of fluorescein and its metabolites in an in vivo rat model using multiphoton microscopy and fluorescent lifetime imaging (FLIM). El-Mashtoly et al [8] demonstrated the use of Raman microscopy in tracking the cellular distribution of label-free erlotinib, a tyrosine kinase inhibitor targeting the epidermal growth factor receptor (EGFR) for cancer treatment [9]
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