title: New oligoethylene ester derivatives of 5-iodo-2'-deoxyuridine as dermal prodrugs: synthesis, physicochemical properties, and skin permeation studies.
abstract: Five new oligoethylene ester derivatives (9-13) of 5-iodo-2'-deoxyuridine (IDU) were synthesized and assayed to determine their lipophilicity by both experimental lipophilicity indices (log K') and calculated partition coefficients (CLOGP). In vitro experiments were carried out to evaluate the chemical and enzymatic stability and fluxes 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 fluxes 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 significantly increased the cumulative amount of IDU that penetrated through excised human skin compared with the parent drug (IDU).
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Facoltà di Farmacia, Università degli Studi di Catania, Viale A. Doria 6, 95125 Catania, Italy. boninafi@mbox.unict.it
authors.forename: Francesco Paolo
authors.initials: FP
authors.lastname: Bonina
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Rimoli
authors.forename: Lucia
authors.initials: L
authors.lastname: Avallone
authors.forename: Francesco
authors.initials: F
authors.lastname: Barbato
authors.forename: Marzia
authors.initials: M
authors.lastname: Amato
authors.forename: Carmelo
authors.initials: C
authors.lastname: Puglia
authors.forename: Maurizio
authors.initials: M
authors.lastname: Ricci
authors.forename: Paolo
authors.initials: P
authors.lastname: De Caprariis
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D000818:Animals; D004952:Esters / Q000737:chemistry / Q000493:pharmacokinetics*; D005030:Ethylenes / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D007065:Idoxuridine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics*; D008875:Middle Aged; D019384:Nucleic Acid Synthesis Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics; D011355:Prodrugs / Q000737:chemistry / Q000493:pharmacokinetics*; D012869:Skin Absorption / Q000502:physiology*; D013552:Swine
chemical_list: D004952:Esters; D005030:Ethylenes; D019384:Nucleic Acid Synthesis Inhibitors; D011355:Prodrugs; C036216:ethylene; D007065:Idoxuridine