Percutaneous absorption and anti-inflammatory effect of a substance P receptor antagonist: spantide II

Purpose: There is accumulating evidence that neurogenic mediators such as substance P (SP) and alpha-melanocyte stimulating hormone (alpha-MSH) contribute to inflammation following chemical and thermal injuries or in disease conditions such as psoriasis and contact dermatitis. Spantide II is a peptide with a molecular weight of 1670.2 which binds to neurokinin-1 receptor (NKR-1) and blocks proinflammatory activities associated with SP. The aim of this study was to investigate in vitro permeation and distribution of spantide II through hairless rat skin and the anti-inflammatory effect of topically delivered spantide II in an allergic contact dermatitis (ACD) mouse model.

Methods: The in vitro permeation and distribution of spantide II with or without cysteine HCl (CH) as a penetration enhancer through hairless rat skin was studied using Franz diffusion cells. The anti-inflammatory effect of spantide II was studied by measuring the reduction of ACD in C57BL/6 mice after application of spantide II as a topical solution.

Results: The skin permeation experiments with or without cysteine HCl (as penetration enhancer) showed no detectable levels of spantide II permeation across rat skin over a period of 48 h. Cysteine HCl significantly increased the distribution of spantide II in skin layers; also, the reduction in ACD response was significantly higher with the formulation containing cysteine HCl (p < 0.05). Spantide II at different concentrations showed a dose-dependent reduction of ACD response in mice.

Conclusions: The current study demonstrates that spantide II can effectively be delivered to epidermis and dermis to exert a significant anti-inflammatory activity on the reduction of inflammation in a mouse model of ACD.