Kumar Sunny, Chen Ming, Anselmo Aaron C, Muraski John A, Mitragotri Samir
Center for Bioengineering, Department of Chemical Engineering, University of California, Santa Barbara, CA, 93106, USA.
Drug Deliv Transl Res. 2015 Oct;5(5):523-30. doi: 10.1007/s13346-015-0232-4.
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.
外用皮质类固醇（TCs）的疗效与安全性平衡取决于其渗透进入皮肤并在皮肤内留存的能力。在此，我们评估了SPACE™肽增强三种模型TCs的表皮递送及定位的能力。开展了体外和体内皮肤渗透研究，以评估在存在各种SPACE™肽制剂的情况下TCs渗透进入皮肤及穿过皮肤的情况。含有游离SPACE™肽的皮质酮外用制剂显著增强了表皮渗透及定位。与水性溶液、氢乙醇溶液和Cortizone™乳膏相比，基于SPACE™肽的制剂在皮肤和接收液中的药物沉积比（疗效/安全性，指示局部摄取与全身摄取的比例）显示出更高的值。质谱分析表明，SPACE™肽与皮质酮结合，这可能解释了其增强的留存效应。与赋形剂对照相比，SPACE™肽还增强了另外两种TCs（氢化可的松和曲安奈德）在皮肤中的留存。一项在小鼠体内开展的研究进一步证实了SPACE™肽增强氢化可的松在皮肤中留存而不导致血药浓度升高的能力。这些结果表明，SPACE™肽是一种有效的制剂添加剂，可增强外用类固醇在皮肤中的定位。
