engleski

Macromolecular prodrugs. XIII. Hydrosolubile conjugates of 17β-estradiol and estradiol-17β- valerate with polyaspartamide polymer

Two hydrosoluble conjugates of 17β-estradiol (ED) and estradiol-17β-valerate (EV) with polyaspartamide polymer were prepared and characterized. ED and EV were first chemically modified and bound to poly[a, b-(N-2- hydroxyethyl-dl-aspartamide)]-poly[a, b-(N-2- aminoethyl-dl-aspartamide)] (PAHA), a hydrosoluble polyaspartamide-type copolymer bearing both hydroxyl and amino groups. ED was first converted to 17-hemisuccinate (EDS) and then bound to PAHA. In the resulting conjugate PAHA-EDS, the estradiol moiety was linked to the polymer through a 2- aminoethylhemisuccinamide spacer. On the other hand, EV was first converted to estradiol-17b- valerate-3-(benzotriazole-1-carboxylate), which readily reacted with amino groups in PAHA affording the polymer-drug conjugate PAHA-EV. In the prepared conjugate PAHA-EV, the estradiol moiety was covalently bound to the polyaspartamide backbone by carbamate linkage, through an ethylenediamine spacer. The polymer- drug conjugates were designed and prepared with the aim to increase water-solubility, bioavailability and to improve drug delivery of the lipophilic estrogen hormone.

estradiol ; polyaspartamide ; poly[a ; b-(N-2-hydroxyethyl-dl-aspartamide)]-poly[a ; b-(N-2-aminoethyl-dl-aspartamide)] ; polymer-drug conjugate

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