Macromolecular prodrugs. XIII. Hydrosoluble 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[α,β-(N-2-hydroxyethyl-DL-aspartamide)]-poly[α,β-(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-17β-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.
University of Zagreb, Faculty of Pharmacy and Biochemistry, Zagreb, Croatia.
Marijana Zovko
MZ
Končič
Branka
B
Zorc
Predrag
P
Novak
D004958:Estradiol / Q000031:analogs & derivatives* / Q000032:analysis / Q000737:chemistry*; D046911:Macromolecular Substances / Q000032:analysis / Q000737:chemistry; D010455:Peptides / Q000032:analysis / Q000737:chemistry*; D011108:Polymers / Q000032:analysis / Q000737:chemistry; D011355:Prodrugs / Q000032:analysis / Q000737:chemistry*; D012995:Solubility
D046911:Macromolecular Substances; D010455:Peptides; D011108:Polymers; D011355:Prodrugs; C017645:polyaspartate; D004958:Estradiol