Enhanced epidermal localization of topically applied steroids using SPACE™ peptide.
The balance of efficacy and safety of topical corticosteroids (TCs) depends on their ability to penetrate into and be retained within the skin. Here, we evaluated the ability of SPACE™ peptide to enhance epidermal delivery and localization of three model TCs. In vitro and in vivo skin penetration studies were performed to evaluate penetration of TCs into and across the skin in the presence of various formulations of SPACE™ peptide. Topical formulations of corticosterone containing free SPACE™ peptide produced significantly enhanced epidermal penetration and localization. Ratio of drug deposition in the skin and receiver (efficacy/safety, indicative of ratio of local to systemic uptake) exhibited higher values for SPACE™ peptide-based formulation as compared to aqueous and hydroethanolic solutions and Cortizone™ cream. Mass spectrometry analysis showed that SPACE™ peptide associates with corticosterone, which may explain its enhanced retention effect. SPACE™ peptide also enhanced dermal retention of two more TCs (hydrocortisone and triamcinolone acetonide) compared to the vehicle control. An in vivo study in mice further established the ability of SPACE™ peptide to enhance skin retention of hydrocortisone without producing elevated blood concentrations. These results show that SPACE™ peptide is an effective additive to the formulation for enhanced skin localization of topical steroids.
Center for Bioengineering, Department of Chemical Engineering, University of California, Santa Barbara, CA, 93106, USA.
Sunny
S
Kumar
Ming
M
Chen
Aaron C
AC
Anselmo
John A
JA
Muraski
Samir
S
Mitragotri
D000279:Administration, Cutaneous; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D016503:Drug Delivery Systems; D004817:Epidermis / Q000378:metabolism*; D005079:Excipients / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D008812:Mice, Hairless; D010455:Peptides / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D013552:Swine; D014018:Tissue Distribution
D000305:Adrenal Cortex Hormones; D005079:Excipients; D010455:Peptides