Exploring unsaturated fatty acid cholesteryl esters as transdermal permeation enhancers.
The intrinsic protective barrier property of skin, one of the major challenges in the design of transdermal drug delivery systems, can be overcome through the use of chemical permeation enhancers (CPEs). Herein, we explore the potential of unsaturated fatty acid (UFA) esters of cholesterol (Chol) viz., oleate, linoleate and linolenate, as transdermal CPEs using tenofovir (TNF) as a model drug. All Chol UFA esters at 1% w/w were found to be more effective enhancers when compared to their respective parent fatty acids (FAs) and saturated FA counterparts. Cholesteryl linolenate (Chol-LLA) showed the most superior performance (enhancement ratio (ER) = 3.71). The greatest ER for Chol-LLA (5.93) was achieved at a concentration of 2% w/w. The histomorphological and transepithelial electrical resistance (TEER) evaluations supported the results of the permeability studies. These findings showed no significant loss in the integrity of the epidermis, with drug and enhancer treatment having temporary effects on the barrier property of the epidermis. Chol UFA esters can therefore be considered as new CPEs for exploitation in topical formulations for various classes of drugs.
Department of Pharmaceutical Sciences, University of KwaZulu-Natal, Private Bag X54001, Durban, 4000, South Africa.
Sanjeev
S
Rambharose
Department of Pharmaceutical Sciences, University of KwaZulu-Natal, Private Bag X54001, Durban, 4000, South Africa. kalhapure@ukzn.ac.za.
Rahul S
RS
Kalhapure
Department of Pharmaceutical Sciences, University of KwaZulu-Natal, Private Bag X54001, Durban, 4000, South Africa.
Mahantesh
M
Jadhav
Department of Pharmaceutical Sciences, University of KwaZulu-Natal, Private Bag X54001, Durban, 4000, South Africa. govenderth@ukzn.ac.za.
Thirumala
T
Govender
D000279:Administration, Cutaneous; D000818:Animals; D002788:Cholesterol Esters / Q000008:administration & dosage / Q000494:pharmacology*; D005227:Fatty Acids / Q000008:administration & dosage / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D017208:Rats, Wistar; D012867:Skin / Q000187:drug effects / Q000378:metabolism*; D012869:Skin Absorption / Q000187:drug effects; D000068698:Tenofovir / Q000008:administration & dosage / Q000493:pharmacokinetics*
D002788:Cholesterol Esters; D005227:Fatty Acids; D000068698:Tenofovir
Chemical permeation enhancers; Cholesterol; Esterification; Tenofovir; Transdermal; Unsaturated fatty acids