Skin penetration underpins the design, efficacy and risk assessment of many high-value products including topical and transdermal drugs, functional personal care products, amongst others. Given the ethical concerns with animal tests, this area is moving towards ex vivo / in vitro studies using excised human skin samples. Nevertheless, current in vitro tests have limited capability in predicting in vivo results. To this end, in silico modelling has been recognised as a promising approach for in vitro – in vivo extrapolation. However, existing models have limited accuracy due to paucity of reliable and quantitative information concerning penetration pathways and penetrant distribution at the site of action in the skin. In addition, in vivo animal studies are still widespread in the pre-clinical stage of drug development. In silico models, if sufficiently accurate, have great promise to help optimise such experiments with potentially substantial reduction of animal use.
To address this challenge, we propose to apply advanced spectroscopic imaging, stimulated Raman scattering (SRS) microscopy, to in vitro assessment of skin penetration. SRS microscopy provides quantitative images with submicron spatial resolution. For the first time, direct measurement of penetration pathways and microscopic distribution of the chemical in the skin will be obtained, which we will use to improve existing in silico models. The integrated modelling-imaging toolkit will significantly improve the in vitro – in vivo extrapolation capability, delivering a more systematic approach for skin penetration assessment. Importantly, the toolkit will help better design and reduce in vivo animal experiments that cannot be completely replaced at present.