A novel skin penetration enhancer: Evaluation by membrane diffusion and confocal microscopy

Purpose. The aim of this study was to determine the in vitro transdermal ef ficacy of a Meyer Zall Laboratories (MZL) oil/water emulsion in two separat e preparations containing the actives, coal tar and the non-steroidal anti inflammatory drug, diclofenac sodium. Method: The release rate of the two a ctive ingredients from MZL dermatological preparations, Exorex and Athru-De rm and four comparator products was determined using an enhancer cell syste m, whilst specific penetration characteristics of the MZL formulation were elucidated using confocal and electron microscopy. The latter properties we re explored at both the organ level, using human skin, as well as at a cell ular level using a melanoma cell line. Results: While the in vitro release rates for all formulations was high, coal tar and diclofenac release from E xorex and Athru-Derm respectively was, at nearly all time intervals, signif icantly higher than from comparator products. Microscopy revealed the prese nce of spherical liposomal type structures in both the MZL lotion and a com parator gel. In the MZL lotion, the majority of these structures, referred hereto as emzaloid particles, were in the order of magnitude of about 50 nm to 1 mu m in diameter with a small minority exceeding these dimensions. Af ter application of Athru-Derm to human skin, intact emzaloid particles of s ubmicron dimensions were detected in the epidermis in association with the cell membranes. The affinity of the MZL lotion for cell membranes was furth er demonstrated with melanoma cells; in addition, the formulation was seen to penetrate even to the nucleus of viable cells. Conclusion: Overall the d ata suggest that the oil/water base in MZL formulations is a highly efficie nt transdermal vehicle able to transport a wide range of indication-specifi c actives to their site of action.