Acta Pharm. 61 (2011) 465-472

full paper

Short communication

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

MARIJANA ZOVKO KONČIĆ, BRANKA ZORC and PREDRAG NOVAK

bzbz@pharma.hr

¹ Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia

² University of Zagreb, Faculty of Science, Department of Chemistry, Zagreb, Croatia

Accepted November 17, 2011

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.

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