Cyclosporine A lipid nanoparticles for oral administration: Pharmacodynamics and safety evaluation

The pharmacodynamic effect and the safety of cyclosporine A lipid nanoparticles (CsA LN) for oral administration were investigated using Sandimmune Neoral (R) as reference. First, the biocompatibility of the unloaded LN on Caco-2 cells was demonstrated. The pharmacodynamic response and blood levels of CsA were studied in Balb/c mice after 5 and 10 days of daily oral administration equivalent to 5 and 15 mg/kg of CsA in different formulations. The in vivo nephrotoxicity after 15 days of treatment at the high dose was also evaluated. The results showed a significant decrease in lymphocyte count (indicator of immunosuppression) for the CsA LN groups which was not observed with Sandimmune Neoral (R). CsA blood levels remained constant over the time after treatment with LN, whereas a proportional increase in drug blood concentration was observed with Sandimmune Neoral (R). Therefore, CsA LN exhibited a better pharmacological response along with more predictable pharmacokinetic information, diminishing the risk of toxicity. Moreover, a nephroprotective effect against CsA related toxicity was observed in the histopathological evaluation when LN containing Tween (R) 80 were administered. Therefore, our preliminary findings suggest LN formulations would be a good alternative for CsA oral delivery, enhancing efficacy and reducing the risk of nephrotoxicity. (C) 2016 Elsevier B.V. All rights reserved.