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Updated: Jun 10, 2026

Development, Characterization, and Evaluation of CAGE-based Ionic Liquid Systems for Transdermal Delivery
Published on: September 26, 2025
In-vitro transdermal penetration of cytarabine and its N4-alkylamide derivatives
Lesetja J Legoabe1, Jaco C Breytenbach, David D N'Da
1Unit for Drug Research and Development, North-West University, Potchefstroom, South Africa. lesetja.legoabe@nwu.ac.za
Objectives:
The aim of this study was to synthesise and determine the transdermal penetration of cytarabine alkylamide derivatives and assess the correlation of flux with physicochemical properties.
Methods:
The alkylamide derivatives of cytarabine were synthesised by acylation at the N4-amino group by the mixed anhydride method. The in-vitro permeation studies were performed using the Franz diffusion cell methodology. Furthermore, partition coefficients (n-octanol-water) and aqueous solubility of the N4-alkylamide derivatives of cytarabine were determined in order to obtain information about their lipophilicity and hydrophilicity.
Key Findings:
The N4-alkylamides of cytarabine (acetyl, butanoyl, hexanoyl, octanoyl, and decanoyl derivatives) showed decreased hydrophilicity and increased lipophilicity. The log D values of the alkylamides were higher than that of the parent compound and increased linearly as the alkyl chain lengthened. N4-hexanoyl-4-amino-1-[(2R,3S,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl] pyrimidin-2-one) showed the highest median steady-state flux (J(ss)) of 89.0 nmol/cm(2) per h in the series, which shows a high statistical difference with the parent compound flux value (3.70 nmol/cm(2) per h).
Conclusions:
The prodrug approach appears to be a promising strategy for the enhancement of transdermal penetration of cytarabine.
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