Development of Calcineurin Inhibitors Loaded Polymeric Nanocomposites Based Gel for Topical Treatment of Psoriasis

Abstract

Calcineurin inhibitors like cyclosporine-A and tacrolimus are macrolide immunosuppressants used treatment of Plaque psoriasis. However, Cyclosporin-A and tacrolimus both have high molecular weight and low water solubility, along with complex cyclic structure which prevents their penetration into skin layers and limits their use in topical therapy of psoriasis. Polymeric nanoparticles loaded with calcineurin inhibitors can enable the formulation of poorly soluble tacrolimus and cyclosporine in an efficient manner. Polymeric nanoparticles were developed and optimized with both the drugs. Statical tool (Quality by Design) was used for the optimization of various product parameters which can impact particle size, zeta newlinepotential and entrapment efficiency. Design matrix was generated by using Minitab software and graphical presentation was done via contour plot, and the formulation was resulted with requisite particle size, zeta potential and entrapment efficiency. Invitro drug release reveled a slow and sustained release of 88.519± 1.10% of drugs up to 14 days with zero order release kinetics with no initial burst release. Optimized drug loaded nanoparticles were finally loaded in to Carbopol-HA binary gel and evaluated for ex-Vivo skin retention and pharmacodynamic newlinestudies by employing imiquimod induced psoriatic plaque model in rats. Prominent reversal of psoriasis from calcineurin inhibitors loaded polymeric nanoparticles gel was reported, indicated by reduced inflammation and scaling without any skin irritation and with higher skin drug retention. In nutshell, polymeric nanoparticles loaded gel formulation is considered to be effective for topical drug targeting without any systemic toxicity caused by calcineurin inhibitors, for the treatment of psoriasis.