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l-Carvyl Esters as Penetration Enhancers for the Transdermal Delivery of 5-Fluorouracil

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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.

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ACKNOWLEDGMENTS

This work was supported by the National Natural Science Foundation of China (no. 30973654) and Research Fund for the Doctoral Program of Higher Education of China (no. 20092134110002).

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning, 110016, People’s Republic of China

    Manli Wang, Honglei Xi, Dongmei Cun, Yang Chen, Yongnan Xu & Liang Fang

  2. College of Pharmacy, Beihua University, 3999 East Binjiang Road, Jilin, Jilin, 132013, People’s Republic of China

    Manli Wang

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  1. Manli Wang
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  2. Honglei Xi
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  3. Dongmei Cun
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Correspondence to Liang Fang.

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Wang, M., Xi, H., Cun, D. et al. l-Carvyl Esters as Penetration Enhancers for the Transdermal Delivery of 5-Fluorouracil. AAPS PharmSciTech 14, 669–674 (2013). https://doi.org/10.1208/s12249-013-9952-2

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