Nanoemulsions as versatile formulations for paclitaxel delivery: peroral and dermal delivery studies in rats.

Pathogenesis of psoriasis involves the keratinocytes in epidermis as well as the angiogenesis involving deeper skin layers. So, the drug delivery strategy should be customized to localize paclitaxel (PCL) inside both layers. In this investigation, in order to achieve penetration of PCL into deeper skin layers while minimizing the systemic escape, a nanoemulsion (NE) was formulated and evaluated its in vivo pharmacokinetic performance. Further, the same formulation was explored for peroral bioavailability enhancement of PCL. Upon dermal application, the drug was predominantly localized in deeper skin layers, with minimal systemic escape. When orally administered as NE, PCL was rapidly absorbed reaching a steady-state value of 3.5 microg/ml in 30 minutes, and steady-state levels persisted up to 18 hours. This has amounted to an absolute bioavailability of 70.62%. Inhibition of P-glycoprotein efflux by D-alpha-tocopheryl polyethyleneglycol 1,000 succinate and labrasol would have contributed to the enhanced peroral bioavailability of PCL. This investigation provides direct evidence on the localization of large molecular weight, lipophilic drug, PCL, in dermis. Further, the NE formulation has enhanced the peroral bioavailability significantly to more than 70%. The developed NE formulation was safe and effective for both peroral and dermal delivery of PCL.