Percutaneous absorption and anti-inflammatory effect of a substance P receptor antagonist: Spantide II
Percutaneous absorption and anti-inflammatory effect of a substance P receptor antagonist: Spantide II
复制标题
DOI：
10.1023/b:pham.0000012157.80716.73
复制
发表时间：
2004-01-01
影响因子：
3.7
通讯作者：
Singh, M
中科院分区：
文献类型：
--
作者：
Babu, RJ;Kikwai, L;Singh, M
目的.越来越多的证据表明，神经原性介质如P物质（SP）和α-黑素细胞刺激激素（α-MSH）有助于化学和热损伤后的炎症或银屑病和接触性皮炎等疾病。Spantide II是一种分子量为1670.2的肽，可与神经激肽-1受体（NKR-1）结合并阻断SP的促炎活性。本研究的目的是研究Spantide II通过无毛大鼠皮肤的体外渗透和分布，以及局部给药的Spantide II在变应性接触性皮炎（ACD）小鼠模型中的抗炎作用。用Franz扩散池研究了Spantide II在盐酸半胱氨酸（CH）和不加CH作为透皮促进剂的情况下通过无毛大鼠皮肤的体外渗透和分布。通过测定C57 BL/6小鼠局部应用Spantide II后ACD的减少来研究Spantide II的抗炎作用。使用或不使用盐酸半胱氨酸（作为渗透增强剂）的皮肤渗透实验显示，在48小时内，未检测到Spantide II透过大鼠皮肤的渗透水平。半胱氨酸盐酸盐显著增加了Spantide II在皮肤层中的分布;此外，ACD反应的降低在含有半胱氨酸盐酸盐的制剂中显著更高（p < 0.05）。Spantide II在不同浓度下呈剂量依赖性降低小鼠ACD反应。目前的研究表明，spantide II可以有效地递送到表皮和真皮，以在ACD小鼠模型中对炎症的减少发挥显著的抗炎活性。
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.