New oligoethylene ester derivatives of 5-iodo-2′-deoxyuridine as dermal prodrugs: Synthesis, physicochemical properties, and skin permeation studies
✍ Scribed by Francesco Paolo Bonina; Maria Grazia Rimoli; Lucia Avallone; Francesco Barbato; Marzia Amato; Carmelo Puglia; Maurizio Ricci; Paolo De Caprariis
- Publisher
- John Wiley and Sons
- Year
- 2002
- Tongue
- English
- Weight
- 183 KB
- Volume
- 91
- Category
- Article
- ISSN
- 0022-3549
- DOI
- 10.1002/jps.1174
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✦ Synopsis
Five new oligoethylene ester derivatives (9±13) of 5-iodo-2 0 -deoxyuridine (IDU) were synthesized and assayed to determine their lipophilicity by both experimental lipophilicity indices (log K 0 ) and calculated partition coef®cients (CLOGP).
In vitro experiments were carried out to evaluate the chemical and enzymatic stability and ¯uxes through excised human skin of these new IDU derivatives. Esters 9±13 showed increased lipophilicity compared with the parent drug (IDU), had good stability in phosphate buffer (pH 7.4), and were readily hydrolyzed by porcine esterase. No correlation between lipophilicity and skin permeation ¯uxes of synthesized esters 9±13 was observed. Results from in vitro percutaneous absorption studies showed that, among all esters synthesized, only esters 9 and 10 signi®cantly increased the cumulative amount of IDU that penetrated through excised human skin compared with the parent drug (IDU).