Nanostructured lipid carrier based dermal gel of cyclosporine for atopic dermatitis-in vitro and in vivo evaluation

Abstract

Cyclosporine is a gold standard for the treatment of atopic dermatitis. Patients demand extended therapy without adverse effects as atopic dermatitis is a chronic condition. The objective of the study was to formulate and evaluate nanostructured lipid carriers (NLC) based dermal gel of cyclosporine to improve transdermal permeation and achieve targeted delivery. Based on drug solubility, excipients were selected for NLCs, namely; Compritol ATO 888®, Gelucire 44/14® as solid lipids, Miglyol 812 N® as liquid lipid and Solutol HS 15® as surfactant. 22 full-factorial design was used for statistical optimization and optimized batch (NLC-01) with particle size 265.6 nm and zeta potential −29.9 mV incorporated into Carbopol-934 gel to prepare cyclosporine NLC based gel. The pH of the gel was found in the range of 5.2–5.5 which was suitable for skin application and in vitro diffusion study showed complete drug release at the end of 6 h. In skin irritation studies, NLC gel and placebo gel did not cause any redness or irritation to the rat skin. Further, NLC based gel was applied for one week on dermatitis-induced rat skin. Post-NLC based gel treatment, the disappearance of erythema and approximately two-fold reduction in ear flap thickness was observed compared to the disease control group. Therefore, NLC based cyclosporine gel can be explored as an alternative dermal treatment of atopic dermatitis.