In vitro topical application and in vivo pharmacodynamic evaluation of nonivamide hydrogels using Wistar rat as an animal model.
Nonivamide, a so-called synthetic capsaicin, is a substitute for capsaicin which has a similar chemical structure and pharmacological activities as those of capsaicin. The purposes of this study were to explore the in vivo pharmacodynamic responses of nonivamide in hydrogels using Wistar rat as an animal model and to correlate the in vivo results with in vitro topical application. The incorporation of Pluronic F-127 polymer into hydrogels resulted in retarded release of nonivamide. Chitosan and carboxymethylcellulose hydrogels produced higher levels of in vitro nonivamide permeation and skin distribution. The in vivo effects of nonivamide on skin perturbation and vasodilation were found to differ depending on dose and duration after topical application. Quantification of transepidermal water loss was demonstrated to correlate with the measured in vitro skin distribution of nonivamide. The various doses of nonivamide in the hydrogels did not markedly influence erythematous reactions of skin as determined by colorimetric measurements. Hydrogel formulations of nonivamide delivered more drug to the skin and produced greater pharmacodynamic activities than did cream bases of capsaicin.
Fang
Jia-You
JY
Graduate Institute of Natural Products, Chang Gung University, 259 Wen-Hwa 1st Road, Kwei-Shan, Tao-Yuan, Taiwan. fajy@mail.cgu.edu.tw
Leu
Yann-Lii
YL
Wang
Ying-Yue
YY
Tsai
Yi-Hung
YH
D000287:Administration, Topical; D000818:Animals; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000494:pharmacology; D020100:Hydrogels / Q000493:pharmacokinetics* / Q000494:pharmacology; D008297:Male; D023421:Models, Animal; D051381:Rats; D017208:Rats, Wistar; D012869:Skin Absorption / Q000187:drug effects* / Q000502:physiology*
D020100:Hydrogels; D002211:Capsaicin; C040937:nonivamide