Topical delivery of Cyclosporine A into the skin using SPACE-peptide

Cyclosporine A (CsA) is used for the treatment of psoriasis; however systemic administration of CsA is potentially life threatening and there are long-term side effects. Topical application of CsA has the potential to overcome this hurdle; however, its use is limited by poor water solubility and low permeability. Here, we report the use of a physical mixture of SPACE-peptide and CsA in an aqueous ethanol solution to enhance the dermal absorption of the drug. The aqueous ethanol solution (hydroethanolic solution) containing 5 mg/mL CsA and 50 mg/mL of free SPACE-peptide (SP50) delivered about 30% of topically applied CsA into the porcine skin in vitro and led to an approximately 9-fold (p < 0.01) increase in accumulation in viable epidermis compared to the hydroethanolic solution without SPACE-peptide (control group). In vivo biodistribution and pharmacokinetic studies performed using SKH1 hairless mice also confirmed the efficacy of SP50 in dermal delivery of CsA and also demonstrated its advantages over other routes in terms of minimizing its systemic absorption. Topical application of SP50 significantly increased the localization of CsA in the target skin (113.1 +/- 13.6 (mu g/g)/mg) compared to all other groups (p < 0.01). In addition, SP50 led to significantly higher skin/blood ratio (443.4 +/- 181.5) and skin/liver ratio (1059.5 +/- 110.8) of CsA compared to all other groups (p < 0.01). The SP50 formulation reported here offers a promising approach for the dermal delivery of CsA. (C) 2014 Elsevier B.V. All rights reserved.