Antibacterial activity and cytotoxicity of PEGylated poly(amidoamine) dendrimers.
Lopez. Analette I AI; Reins. Rose Y RY; McDermott. Alison M AM; Trautner. Barbara W BW; Cai. Chengzhi C
Key Findings
- Unmodified G3 and G5 PAMAM dendrimers kill P. aeruginosa and S. aureus at similar levels to LL‑37.
- antibacterial strength, especially against Gram‑positive bacteria, but dramatically cuts their toxicity to human corneal cells.",
Practical Outcomes
- For now, the findings are mainly of interest to developers of new antimicrobial eye drops or coatings, not something biohackers can apply directly. It does suggest that future products might offer strong antibacterial effects with lower side‑effects compared to peptide‑based treatments.
Summary
The study shows that certain synthetic molecules called PAMAM dendrimers can kill eye‑infection bacteria about as well as the natural antimicrobial peptide LL‑37, but they can also be tweaked with a small amount of PEG to make them less harmful to human eye cells while still being effective against some bacteria. However, this research is about lab‑made polymers, not a supplement or protocol you can use right now.
Abstract
We have investigated the antibacterial activity and cytotoxicity of a series of amino-terminated poly(amidoamine) (PAMAM) dendrimers modified with poly(ethylene glycol) (PEG) groups. The antibacterial activity of the PAMAM dendrimers and their derivatives against the common ocular pathogens, Pseudomonas aeruginosa and Staphylococcus aureus, was evaluated by their minimum inhibitory concentrations (MICs). For the unmodified third and fifth generation (G3 and G5) amino-terminated dendrimers, the MICs against both P. aeruginosa and S. aureus were in the range of 6.3-12.5 microg mL(-1), comparable to that of the antimicrobial peptide LL-37 (1.3-12.5 microg mL(-1)) and within the wide range of 0.047-128 microg mL(-1) for the fluoroquinolone antibiotics. PEGylation of the dendrimers decreased their antibacterial activities, especially for the Gram-positive bacteria (S. aureus). The reduction in potency is likely due to the decrease in the number of protonated amino groups and shielding of the positive charges by the PEG chains, thus decreasing the electrostatic interactions of the dendrimers with the negatively-charged bacterial surface. Interestingly, localization of a greater number of amino groups on G5 vs. G3 dendrimers did not improve the potency. Significantly, even a low degree of PEGylation, e.g. 6% with EG(11) on G3 dendrimer, greatly reduced the cytotoxicity towards human corneal epithelial cells while maintaining a high potency against P. aeruginosa. The cytotoxicity of the PEGylated dendrimers to host cells is much lower than that reported for antimicrobial peptides. Furthermore, the MICs of these dendrimers against P. aeruginosa are more than two orders of magnitude lower than other antimicrobial polymers reported to date. These results motivate further exploration of the potential of cationic dendrimers as a new class of antimicrobial agents that may be less likely to induce bacterial resistance than standard antibiotics.
Study Information
pubmed
2009
2009-07-03T00:00:00.000Z
10.1039/b904746h
132
62