摘要：Two hydrosoluble conjugates of 17b-estradiol (ED) and estradiol-17b-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.
