Poster Presenter
In vitro Transdermal Absorption of Cytarabine and its N4-Alkylamides
Derivatives
Lesetja J. Legoabe, David D. N’
Da, Jaco C. Breytenbach, Jeanetta
du Plessis
South Africa
The aim of this study was to synthesize and determine the transdermal
delivery of cytarabine alkylamine derivatives and assess the correlation
of flux with physicochemical properties. The alkylamide derivatives
of cytarabine were synthesized by acylation at N4-amino group by mixed
anhydride method. The in vitro permeation studies were performed using
Franz diffusion cell methodology. Furthermore, partition coefficients
(n-octanol-water) and aqueous solubility of N4-alkylamide derivatives
of cytarabine were determined in order to obtain information about
their lipophilicity and hydrophilicity. Alkylamides (2)-(6) showed
decreased hydrophilicity and increased lipophilicity. The logD values
of the alkylamides were higher than that of the parent compound and
increased linearly as the alkyl chain lengthened. Compound (4) showed
the highest median steady-state flux (Jss)
of 89.0 nmol/cm2/h
in the series, which shows a high statistical difference with the
parent compound flux value (3.70 nmol/cm2/h).
The prodrug approach appears to be a promising strategy for the enhancement
of transdermal absorption of cytarabine.
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