Unraveling the drug distribution in brain enabled by MALDI MS imaging with laser-assisted chemical transfer

Accurate localization of central nervous system(CNS)drug distribution in the brain is quite challenging to matrix-assisted laser desorption/ionization(MALDI)mass spectrometry imaging(MSI),owing to the ionization competition/suppression of highly abundant endogenous biomolecules and MALDI matrix.Herein,we developed a highly efficient sample preparation technique,laser-assisted chemical transfer(LACT),to enhance the detection sensitivity of CNS drugs in brain tissues.A focused diode laser source transilluminated the tissue slide coated with α-cyano-4-hydroxycinnamic acid,an optimal matrix to highly absorb the laser radiation at 405 nm,and a very thin-layer chemical film mainly containing drug molecule was transferred to the acceptor glass slide.Subsequently,MALDI MSI was performed on the chemical film without additional sample treatment.One major advantage of LACT is to minimize ionization competition/suppression from the tissue itself by removing abundant endogenous lipid and protein components.The superior performance of LACT led to the successful visualization of regional distribution patterns of 16 CNS drugs in the mouse brain.Furthermore,the dynamic spatial changes of risperidone and its metabolite were visualized over a 24-h period.Also,the brain-to-plasma(B/P)ratio could be obtained according to MALDI MSI results,providing an alternative means to assess brain penetration in drug discovery.

CO_(2)fractional laser-assisted transdermal delivery of silk nanofiber carriers in a rabbit ear hypertrophic scar model

Background:Hypertrophic scars are skin fibrotic diseases,characterized by fibroblast hyperprolif-eration and excessive accumulation of extracellular matrix.However,topical drug application for hypertrophic scars are unsatisfactory.The purpose of this study was to explore the permeability of silk nanofiber hydrogels(SNFs)loaded with rhodamine 6G(R6G)and rhodamine 110(R110)mediated by CO_(2)fractional laser irradiation into hypertrophic scar tissues.Methods:In this work,R6G and R110 were chosen as hydrophilic and hydrophobic model molecules.They were loaded inside SNFs.In vivo rabbit ear hypertrophic scars were treated with CO_(2)fractional laser irradiation and then R6G/R110-laden SNFs were applied to the scars to evaluate their synergetic effect on drug penetration efficiency.Their permeability was quantified by fluorescence intensity and measured by confocal laser scanning microscopy on days 1,3,5 and 7.More specifically,the thermal coagulation zone(CZ)and its surrounding area(peri-CZ)caused by the thermal coagulation of the laser were discussed separately.Results:Our data indicated that the SNFs promoted the penetration of R6G but not that of R110 in the peri-CZ on day 1 when combined with laser irradiation.Interestingly,both R6G and R110 were abundant in the CZ and remained stable on days 1,3 and 5.Moreover,rapid re-epithelialization hindered the long-term permeability of both drugs.Conclusion:Combining CO_(2)fractional laser irradiation with SNF drug delivery could improve the efficiency of hydrophilic drug delivery within 24 h before total re-epithelialization.