Macromolecular prodrugs XI. Synthesis and characterization of polymer-estradiol conjugate.
Estradiol-3-benzoate (EB), an ester derivative of the main oestrogen hormone estradiol, was chemically modified and bound to poly(alpha,beta-(N-2-hydroxyethyl-DL-aspartamide))-poly(alpha,beta-(N-2-aminoethyl-DL-aspartamide)) copolymer (PAHA). EB was first converted to estradiol-3-benzoate-17-(benzotriazole-1-carboxylate), which readily reacted with amino groups in PAHA affording the polymer-drug conjugate PAHA-EB. In PAHA-EB estradiol moiety was covalently bound to the polymeric carrier by carbamate linkage, through non-toxic ethylenediamine spacer. The synthesized compound is a potential hydrosoluble estradiol prodrug.
Zovko
M
M
Faculty of Pharmacy and Biochemistry, University of Zagreb, A. Kovacića, 1, 10000 Zagreb, Croatia.
Zorc
B
B
Novak
P
P
Tepes
P
P
Cetina-Cizmek
B
B
Horvat
M
M
D002626:Chemistry, Pharmaceutical / Q000379:methods; D016503:Drug Delivery Systems / Q000379:methods / Q000639:trends; D004958:Estradiol / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D046911:Macromolecular Substances / Q000138:chemical synthesis*; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis*; D011108:Polymers / Q000138:chemical synthesis*; D011355:Prodrugs / Q000138:chemical synthesis*; D013678:Technology, Pharmaceutical / Q000379:methods
D046911:Macromolecular Substances; D010455:Peptides; D011108:Polymers; D011355:Prodrugs; C008965:alpha,beta-poly((2-hydroxyethyl)-aspartamide); C074283:estradiol 3-benzoate; D004958:Estradiol