title: Topical delivery of Cyclosporine A into the skin using SPACE-peptide.
abstract: 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 5mg/mL CsA and 50mg/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(μg/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.
authors.affiliation: Center for Bioengineering, Department of Chemical Engineering, University of California, Santa Barbara, CA 93106, United States.
authors.forename: Ming
authors.initials: M
authors.lastname: Chen
authors.affiliation: Center for Bioengineering, Department of Chemical Engineering, University of California, Santa Barbara, CA 93106, United States.
authors.forename: Sunny
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Center for Bioengineering, Department of Chemical Engineering, University of California, Santa Barbara, CA 93106, United States.
authors.forename: Aaron C
authors.initials: AC
authors.lastname: Anselmo
authors.affiliation: Center for Bioengineering, Department of Chemical Engineering, University of California, Santa Barbara, CA 93106, United States.
authors.forename: Vivek
authors.initials: V
authors.lastname: Gupta
authors.affiliation: Convoy Therapeutics, 405 W Cool Drive, Suite 107, Oro Valley, AZ 85704, United States.
authors.forename: Deborah H
authors.initials: DH
authors.lastname: Slee
authors.affiliation: Convoy Therapeutics, 405 W Cool Drive, Suite 107, Oro Valley, AZ 85704, United States. Electronic address: jmuraski@convoytx.com.
authors.forename: John A
authors.initials: JA
authors.lastname: Muraski
authors.affiliation: Center for Bioengineering, Department of Chemical Engineering, University of California, Santa Barbara, CA 93106, United States; Convoy Therapeutics, 405 W Cool Drive, Suite 107, Oro Valley, AZ 85704, United States. Electronic address: samir@engineering.ucsb.edu.
authors.forename: Samir
authors.initials: S
authors.lastname: Mitragotri
mesh_terms: D000287:Administration, Topical; D000818:Animals; D057846:Cell-Penetrating Peptides / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical; D016572:Cyclosporine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004337:Drug Carriers; D016503:Drug Delivery Systems; D000431:Ethanol; D005079:Excipients; D066298:In Vitro Techniques; D051379:Mice; D008812:Mice, Hairless; D012869:Skin Absorption / Q000187:drug effects*; D012996:Solutions; D012997:Solvents; D013552:Swine; D014018:Tissue Distribution
chemical_list: D057846:Cell-Penetrating Peptides; D004337:Drug Carriers; D005079:Excipients; D012996:Solutions; D012997:Solvents; D000431:Ethanol; D016572:Cyclosporine
keywords: Biodistribution; Cyclosporine A; Skin penetrating peptide; Topical delivery