Synthesis and Characterization of Polyester-Based Dendrimers Containing Peripheral Arginine or Mixed Amino Acids as Potential Vectors for Gene and Drug Delivery

摘要

Macromolecular systems with well-defined sizes, shapes and high controlled architecture like dendrimers are of eminent interest in nanomedical applications such as drug delivery, gene transfection, and imaging. In this paper versatile protocols for the synthesis of polyester-based, hydrolysable, polycationic dendrimers have been setup. Fourth and fifth generation dendrimers equipped with several peripheral hydroxyl groups were prepared from 2, 2-bis(hydroxymethyl) propanoic acid. They were successfully esterified with arginine alone or mixed with lysine or O-methyltyrosine and with dipeptide arginine-glycine and seven polycationic dendrimers were finally obtained as hydrochlorides. Their structures and composition were confirmed by NMR analysis and by experimental molecular weight computed by volumetric titration and their buffer capacity was higher than fourth generation polyamidoamine (G4-PAMAM) derivatives taken as reference. The synthesized dendrimers harmonize a polycationic character and a buffer capacity which presuppose a good transfection efficiency with a degradable scaffold thus appearing as a promising team of new non-toxic vectors for biomedical applications.