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

Abstract

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.

• Authors: R Jayachandra Babu, Loice Kikwai, Lasha T Jaiani, Narayanasamy Kanikkannan, Cheryl A Armstrong, John C Ansel, Mandip Singh
• Journal: Pharmaceutical research (Pharm Res) Vol. 21 Issue 1 Pg. 108-13 (Jan 2004) ISSN: 0724-8741 [Print] United States
• PMID: 14984264 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Neurokinin-1 Receptor Antagonists
• Receptors, Neurokinin-1
• spantide II
• Substance P

Topics

• Administration, Cutaneous
• Animals
• Anti-Inflammatory Agents, Non-Steroidal (administration & dosage, pharmacokinetics)
• Chromatography, High Pressure Liquid
• Dermatitis, Allergic Contact (drug therapy, metabolism, pathology)
• Dose-Response Relationship, Drug
• Female
• In Vitro Techniques
• Male
• Mice
• Mice, Inbred C57BL
• Neurokinin-1 Receptor Antagonists
• Rats
• Receptors, Neurokinin-1 (metabolism)
• Skin Absorption (drug effects, physiology)
• Substance P (administration & dosage, analogs & derivatives, isolation & purification, pharmacokinetics)
• Tissue Distribution