Saturated long-chain esters of isopulegol as novel permeation enhancers for transdermal drug delivery.
OBJECTIVE
Saturated long-chain esters of isopulegol were synthesized and their activities as permeation enhancers for transdermal delivery of amlodipine and flurbiprofen were investigated, in contrast to the saturated fatty acids and isopulegol, as well as their physical mixtures.


METHODS
In vitro permeation experiments, confocal laser scanning microscopy (CLSM) and attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy were introduced to investigate the regulation of enhancers in the skin permeability and biophysical properties. With in vitro cytotoxicity test and in vivo erythema model, the skin irritation of enhancers was evaluated.


RESULTS
The esters significantly increased the permeation of amlodipine and flurbiprofen, whereas saturated fatty acids and isopulegol had no such effect and even decreased the drug permeation when they were used alone or in combination. These results were supported by CLSM and ATR-FTIR studies, which revealed that only the esters could decrease the order of the alkyl chains in the skin lipids. Additionally, almost no skin irritation and cytotoxicity were observed for these esters.


CONCLUSIONS
Saturated long-chain esters of isopulegol are shown to be suitable permeation enhancers for transdermal drug delivery. Covalent attachment of isopulegol and saturated fatty acids might represent a promising strategy to design novel and potent permeation enhancers.
Department of Pharmaceutical Science, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning, 110016, China.
Yang
Y
Chen
Dongmei
D
Cun
Peng
P
Quan
Xiaochang
X
Liu
Wenjia
W
Guo
Lihua
L
Peng
Liang
L
Fang
D000279:Administration, Cutaneous; D000818:Animals; D000081005:Cyclohexane Monoterpenes; D016503:Drug Delivery Systems / Q000379:methods*; D004952:Esters; D005227:Fatty Acids / Q000008:administration & dosage* / Q000378:metabolism; D008297:Male; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar; D012869:Skin Absorption / Q000187:drug effects* / Q000502:physiology; D013729:Terpenes / Q000008:administration & dosage* / Q000378:metabolism
D000081005:Cyclohexane Monoterpenes; D004952:Esters; D005227:Fatty Acids; D013729:Terpenes; C409816:isopulegol