Synthesis of macromolecular prodrugs of procaine, histamine and isoniazid.
The attachment of various drugs bearing -NH2 groups to poly-alpha,beta-aspartic acid as a biodegradable carrier afforded in good yields macromolecular prodrugs which were characterized with respect to composition and drug load by spectroscopic and analytical methods. N-Ethyl-N'-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) in an aqueous medium proved to be useful in the attachment reaction. Isoniazid, procaine and histamine were covalently coupled as pendant groups onto poly-alpha,beta-aspartic acid via an amide bond. In principle, controlled release of the aforementioned drugs can be achieved by biodegradation of the polymer or by cleavage of covalently bound polymer-drug conjugates.
Giammona
G
G
Giannola
L I
LI
Carlisi
B
B
Bajardi
M L
ML
D055598:Chemical Phenomena; D002621:Chemistry; D006632:Histamine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D007538:Isoniazid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D008970:Molecular Weight; D011343:Procaine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D011355:Prodrugs / Q000138:chemical synthesis*
D011355:Prodrugs; D011343:Procaine; D006632:Histamine; D007538:Isoniazid