Percutaneous absorption and anti-inflammatory effect of a substance P receptor antagonist: spantide II.
OBJECTIVE
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.
Babu
R Jayachandra
RJ
College of Pharmacy and Pharmaceutical Sciences, Florida A & M University, Tallahassee, Florida 32307, USA.
Kikwai
Loice
L
Jaiani
Lasha T
LT
Kanikkannan
Narayanasamy
N
Armstrong
Cheryl A
CA
Ansel
John C
JC
Singh
Mandip
M
D000279:Administration, Cutaneous; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D017449:Dermatitis, Allergic Contact / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D064729:Neurokinin-1 Receptor Antagonists; D051381:Rats; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects / Q000502:physiology*; D013373:Substance P / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D000894:Anti-Inflammatory Agents, Non-Steroidal; D064729:Neurokinin-1 Receptor Antagonists; D018040:Receptors, Neurokinin-1; C065446:spantide II; D013373:Substance P