l-Carvyl esters as penetration enhancers for the transdermal delivery of 5-fluorouracil.

Abstract

To develop effective and safe penetration enhancers, a series of l-carvyl esters, namely, 5-isopropenyl-2-methylcyclohex-2-en-1-yl heptanoate (C-HEP), 5-isopropenyl-2- methylcyclohex-2-en-1-yl octanoate (C-OCT), 5-isopropenyl-2-methylcyclohex-2-en-1-yl decanoate (C-DEC), 5-isopropenyl-2-methylcyclohex-2-en-1-yl dodecanoate (C-DOD), 5-isopropenyl-2-methylcyclohex-2-en-1-yl tetradecanoate (C-TET), and 5-isopropenyl-2-methylcyclohex-2-en-1-yl palmitate (C-PAL), was synthesized from l-carveol and saturated fatty acids (C7-C16). The volatility of l-carveol and l-carvyl esters was evaluated by a live weight loss experiment. The enhancing effects of l-carvyl esters on 5-fluorouracil (FU) were investigated in the in vitro permeation experiment on rat skin. The stratum corneum (SC) uptakes of the enhancers were tested in vitro by gas chromatography. Only the l-carvyl esters with a moderate SC uptake, namely, C-OCT (C8), C-DEC (C10), and C-DOD (C12), showed a potential to enhance FU skin permeation. An evident parabolic relationship was found between the permeation enhancement of FU and the SC uptake of the l-carvyl esters. The l-carvyl esters with a chain length of C8-C12 seemed to be favorable for FU.

• Authors: Manli Wang, Honglei Xi, Dongmei Cun, Yang Chen, Yongnan Xu, Liang Fang
• Journal: AAPS PharmSciTech (AAPS PharmSciTech) Vol. 14 Issue 2 Pg. 669-74 (Jun 2013) ISSN: 1530-9932 [Electronic] United States
• PMID: 23543605 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antimetabolites, Antineoplastic
• Cyclohexane Monoterpenes
• Esters
• Fatty Acids
• Monoterpenes
• carveol
• Fluorouracil

Topics

• Administration, Cutaneous
• Animals
• Antimetabolites, Antineoplastic (administration & dosage, chemistry, metabolism)
• Chemistry, Pharmaceutical
• Chromatography, Gas
• Cyclohexane Monoterpenes
• Esters (chemistry, metabolism, pharmacology)
• Fatty Acids (chemistry, metabolism, pharmacology)
• Fluorouracil (administration & dosage, chemistry, metabolism)
• Male
• Molecular Structure
• Monoterpenes (chemistry, metabolism, pharmacology)
• Permeability
• Rats
• Rats, Wistar
• Skin (drug effects, metabolism)
• Skin Absorption (drug effects)
• Structure-Activity Relationship
• Technology, Pharmaceutical (methods)
• Volatilization