Evaluation of drug delivery to intact and porated skin by coherent Raman scattering and fluorescence microscopies

Abstract

Stimulated Raman scattering microscopy was used to assess the permeation of topically applied drugs and formulation excipients into porcine skin. This chemically selective technique generates high-resolution 3D images, from which semi-quantitative information may be elucidated. Ibuprofen, applied as a close-to-saturated solution in propylene glycol, was directly observed to crystallise in/on the skin, as the co-solvent permeated more rapidly, resulting in precipitation of the drug. Coherent Raman scattering microscopy is also an excellent tool, in conjunction with more conventional confocal fluorescence microscopy, with which to image micro/nanoparticle-based formulations. Specifically, the uptake of particles into thermal ablation transport pathways in the skin has been examined.

The application of ATR-FTIR spectroscopy and multivariate data analysis to study drug crystallisation in the stratum corneum

“…Several reports have shown the detection of drug crystals on mammalian skin but little is known about how the phenomenon actually happens in the skin [5,6]. This study explored the combined abilities of (i) ATR-FTIR spectroscopy to detect drug crystals in skin samples and (ii) multivariate data analysis for differentiation of spectral characteristics descriptive of the physical state of the model drug.…”

“…Saar et al [5] showed the formation of ibuprofen crystals on excised mouse skin using simulated Raman scattering (SRS) imaging, following application of a solution of deuterated ibuprofen in propylene glycol (PG). More recently, Belsey et al [6] observed large ibuprofen crystals on porcine skin 30 min post application of a saturated solution of ibuprofen in PG using the same imaging technique. However, actual location of crystals in the skin remains a limitation of SRS imaging as is the apparent requirement for deuteration of the active of interest.…”

“…Because of the complexity of the spectral datasets which are typically collected, multivariate data analysis is a very useful tool to study subtle differences in IR spectra. Hierarchical cluster analysis (HCA) and principal component analysis (PCA) 6 have both been used to classify spectroscopic results based on their dissimilarity and variations [12].…”

Ethanol induces the formation of water-permeable defects in model bilayers of skin lipids

“…Thus, bilayers at different depths will be exposed to different concentrations of the permeating molecules and determining the effective concentrations of each of the formulation ingredients in the SC is extremely challenging. Although recent progress has been made using Raman scattering microscopy 3 , only semi-quantitative information may be elucidated at the current time. Experiments reported in the literature have investigated the permeation of selected compounds in EtOH-containing mixtures from very low concentrations of EtOH up to pure EtOH, for examples see Ref 4 .…”

A Method for Quantification of Penetration of Nanoparticles through Skin Layers Using Near-Infrared Optical Imaging

“…When working with dermatological applications of nanoparticles, therefore, it would be useful to have a method for imaging fluorescence that (1) was free of interfering background signal, (2) operated on a macro (in millimeters) viewing scale, rather than either a micro or in vivo scale, and (3) also able to quantify the signal intensity. Recent methods reported include techniques, such as Raman spectroscopy, which has been used to quantify the penetration of nanoparticles into skin at micro-scale depths [13,14].…”