Influence of protamine shell on nanoemulsions as a carrier for cyclosporine-A skin delivery.

Novel protamine-based nanosystems have been studied for cyclosporine-A (CsA) skin delivery. Core-shell structure systems have been developed to this end. These vehicles have particles sizes of 200-300 nm, a low polydispersity index and a zeta potential which varies between -16 mV and +35 mV. The resulting four nanosystems efficiently encapsulated CsA in their oily nucleus (60-80%) and released this drug in a controlled manner. These formulations have shown a high stability in aqueous suspension in storage conditions at 4 °C (for at least 21 months) and in acetate buffer at a physiological temperature of 37 °C (for at least 24 h). Ex vivo transdermal diffusion experiments using Franz diffusion cells and 2- to 3-day-old pig skin as a biological barrier were performed. All nanoformulations designed produced an increase in CsA transdermal delivery and two of these nanosystems presented a marked promoting effect; the more relevant parameters were smaller particle size (200 ± 7 nm) and negative superficial charge. Finally, the ability of these nanosystems to enhance retention of CsA in the skin was also studied. The protamine disposition in the shell influenced CsA skin retention. Therefore, the incorporation of CsA into the nanosystems studied here makes them suitable vehicles for CsA transdermal administration.