Development of cyclosporine-loaded nanoemulsion for topical treatment of psoriasis

Abstract

Psoriasis is an autoimmune disease in which the symptoms are obviously appeared on the patient's body with thick, red/ salmon colour and dry patches. Clinically, topical treatment has been the first-line treatment for psoriasis, whether or not the systemic and phototherapy is required. Currently, cyclosporine is one of the standard oral medications used for moderate to a severe case of psoriasis. However, through oral delivery, it cannot be used for a long period and causes bad effects. Thus, a new delivery system of cyclosporine is in need to be developed to overcome its toxic effects by skipping the first pass body metabolism. A nanoemulsion colloidal system, as the main carrier for big, non-water-soluble cyclosporine, is believed could help in the delivery of activities through the stratum corneum of the skin layer. Nanoemulsion system, which mainly consists of oil phase (a mixture of virgin coconut oil, nutmeg oil, and cyclosporine), aqueous phase, and surfactant, was successfully being developed by using Mixture Experimental Design optimization tool with droplet size range between 110-160 nm. Stability studies were carried out with respect to; pH, storage at different temperatures, coalescence and Ostwald ripening mechanism, free-thaw cycle, and FTIR analysis. From the obtained results, this newly-developed nanoemulsion containing cyclosporine was proven to be stable and successfully maintained its physicochemical characteristics even after 3 months of storage at 4°C and 25°C temperature. Ostwald ripening mechanism contributed to the instability of the system at 45°C of storage. Introduction of standard cyclosporine, blank nanoemulsion, and nanoemulsion containing cyclosporine to the HaCaT cells in the treatment of MTT assay study has confirmed the safety of the nanoemulsion. Permeation study of the newly-developed nanoemulsion containing cyclosporine showed it was best fitted the Korsmeyer-Peppas kinetic model. In addition, the transepidermal water loss and hydration studies proved the efficacy of cyclosporine-loaded nanoemulsion in increasing the water storage of the volunteers’ normal skin after 3h of application.