New oligoethylene ester derivatives of 5-iodo-2'-deoxyuridine as dermal prodrugs: synthesis, physicochemical properties, and skin permeation studies.
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).
Bonina
Francesco Paolo
FP
Dipartimento di Scienze Farmaceutiche, Facoltà di Farmacia, Università degli Studi di Catania, Viale A. Doria 6, 95125 Catania, Italy. boninafi@mbox.unict.it
Rimoli
Maria Grazia
MG
Avallone
Lucia
L
Barbato
Francesco
F
Amato
Marzia
M
Puglia
Carmelo
C
Ricci
Maurizio
M
De Caprariis
Paolo
P
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
D004952:Esters; D005030:Ethylenes; D019384:Nucleic Acid Synthesis Inhibitors; D011355:Prodrugs; C036216:ethylene; D007065:Idoxuridine