Antibacterial Activities of Poly(amidoamine) Dendrimers Terminated with Amino and Poly(ethylene glycol) Groups

Abstract

Poly(amidoamine) (PAMAM) dendrimer derivatives have been investigated for their biological applications, especially for delivery of drugs, including antimicrobial drugs to eukaryotic cells, but their effects on bacterial cells are largely unexplored. Herein we report that amino-terminated PAMAM dendrimers are highly toxic to the common Gram-negative pathogen Pseudomonas aeruginosa. The concentration that kills 50% of the bacteria (EC50) was in the range of approximately 0.9-1.5 microg/mL for the generation 5, amino-terminated dendrimers with or without partial (43%) coating of poly(ethylene glycol) (PEG). These EC50 values were lower than that ( approximately 1.9-2.8 microg/mL) for LL-37, a potent antimicrobial peptide expressed in a variety of epithelia. On the contrary, the dendrimers were far less toxic (EC50 > 21 microg/mL) to the Gram-positive pathogen Staphylococcus aureus than LL-37 (EC50 = approximately 1.9 microg/mL). In agreement with the previous studies on other cell types, the dendrimers were not cytotoxic to human corneal epithelial cells at the concentrations that were toxic to P. aeruginosa. Our findings indicate that amino-terminated PAMAM dendrimers and their partially PEG-coated derivatives possess attractive antimicrobial properties, particularly against Gram-negative bacteria, thus expanding the potential biological application of the dendrimers.

Amino-Terminated Generation 2 Poly(amidoamine) Dendrimer as a Potential Broad-Spectrum, Nonresistance-Inducing Antibacterial Agent

“…It has been reported that the antibacterial activity is related to the generation of the PAMAM-NH 2 (11,12). Our current results showed that G2.0-4.0 PAMAM-NH 2 had greater antibacterial activity than G1.0 PAMAM-NH 2 , whereas G2.0 PAMAM-NH 2 exhibited comparable or higher antibiotic activities than G3.0 and G4.0 PAMAM-NH 2 .…”

“…Among the PAMAM dendrimers harboring a variety of functional groups, amino-terminated PAMAM dendrimers (PAMAM-NH 2 ) show the strongest antibacterial activity. However, the previous studies primarily investigated the antibacterial activity of generation 3 or higher PAMAM-NH 2 dendrimers on limited bacterial strains in vitro (11,12). However, the higher-generation PAMAM-NH 2 dendrimers often show stronger cytotoxicity, which hinders further exploration of these compounds as antibacterial agents in vivo (13)(14)(15).…”

PAMAM dendrimer - cell membrane interactions

“…Calabretta et al [51] and Lopez et al [52] demonstrated concentration-dependent antibacterial properties of amine terminated PAMAM dendrimers (G3 and G5). With positively charged amine groups, they preferentially bound to bacterial membranes which have a higher charge density than eukaryotic cells.…”

Dendrimers as Antibacterial Agents

“…They are also suggested PAMAM dendrimers as the antimicrobial agents because of the fact that PEG-coated PAMAM derivatives exhibited low toxicity to human corneal epithelial cells (Calabretta et al, 2007). Epidemiologic studies performed in Europe countries report an increase in infectious diseases and bacterial resistance to antibiotics.…”