A novel epidermal mimicking phospholipid vesicle-based permeation assay: EpiPVPA for in vitro permeation evaluation

Phospholipid vesicle-based permeation assay (PVPA) is widely applied as in vitro skin alternative model by mimicking stratum corneum to evaluate the transdermal application of drugs and chemicals. However, it is composed of lipid components only, which suffer from limitations of achieving accurate permeability prediction. To remedy this shortcoming, inactive immortalized human keratinocytes (HaCaT) were integrated as component to construct epidermal-mimicking model: EpiPVPA. The EpiPVPA could tolerate the pH 3-10 as well as up to 30% ethanol and was stable for 2 weeks at 4 ℃. And the permeation evaluation by Franz diffusion test of 14 drugs demonstrated that EpiPVPA model is comparable to porcine skin with strong correlation. After quantitative structure-property relationship (QSPR) analysis of physicochemical descriptors of 14 drugs, HLB, TPSA, and log P were selected as main factors applied to build multiple linear regression (MLR) equation, and the corresponding linear correlation R² was elevated to 0.9010. EpiPVPA model is feasible to be applied to permeation evaluation of drugs and cosmetics.