Synthesis and Characterization of Amino-Functional Polyester Dendrimers Based On Bis-MPA with Enhanced Hydrolytic Stability and Inherent Antibacterial Properties

Abstract

Polyester dendrimers based on 2,2 bis(hydroxymethyl)propionic acid have been reported to be degradable, non-toxic, and exhibit good antimicrobial activity when decorated with cationic charges. However, these systems exhibit rapid depolymerization, from the outer layer inwards in physiological neutral pHs, which potentially restricts their use in biomedical applications. In this study, we present a new generation of amine functional bis-MPA polyester dendrimers with increased hydrolytic stability as well as antibacterial activity for Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli) and Pseudomonas aeruginosa (P. aeruginosa) planktonic bacteria strains. These new derivatives show generally good cytocompatibility for the concentrations they are active toward bacteria, in monocyte/macrophage-like cells (Raw 264.7), and human dermal fibroblasts. Fluoride - promoted esterification chemistry, anhydride chemistry, and click reactions were utilized to produce a library from generations 1-3 and with cationic peripheral groups ranging from 6 to 24 groups, respectively. The dendrimers were successfully purified using conventional purification techniques as well as characterized by matrix-assisted laser desorption ionization time-of-flight mass spectroscopy, nuclear magnetic resonance, and size exclusion chromatography. As proof of synthetic versatility, dendritic-linear-dendritic block copolymer were successfully synthesized to display cysteamine peripheral functionalities as well as the scaffolding ability with biomedically relevant lipoic acid and methoxy polyethylene glycol.