Controlled Topical Delivery of Hydrocortisone and Mannitol Via Select Pathways

In an earlier report (1) we described the controlled follicular delivery of hydrophobic macromolecules from nonionic lipid-based formulations composed of glyceryl dilaurate (GDL), cholesterol (CH), and polyoxyethylene-10-stearyl ether (POE-10). However, the influence of lipid composition on topical delivery of marginally hydrophobic and hydrophilic drugs from these nonionic lipid-based systems has not been investigated. In this report we describe the effect of variation of GDL to POE-10 ratio in the nonionic lipid-based formulations on the extent and route of delivery of hydrocortisone and mannitol, a marginally hydrophobic and hydrophilic model drug, respectively, into and through hairless mouse skin mounted on Franz diffusion cells. The results indicate that the extent of hydrocortisone uptake increased with increasing GDL to POE-10 weight ratio whereas mannitol uptake was quite the opposite and decreased with increasing GDL to POE-10 weight ratio. The diametrically opposite trends for the two drug markers suggests strongly that hydrocortisone and mannitol are transported into and across skin from the nonionic lipid-based formulations via two distinctly different routes. Further, the finding from microautoradiographic studies that the delivery of hydrocortisone from nonionic lipid-based lipid melt formulations was predominantly across the transfollicular route compared to its transport across both the trans-epidermal and transfollicular pathways from nonionic lipid-based liposomes, suggests that it is possible to tailor formulations for specific and targeted delivery across a certain route.