Anti-Biofilm Efficacy of Dual-Action Nitric Oxide-Releasing Alkyl Chain Modified Poly(amidoamine) Dendrimers

Herein, we describe the synthesis of nitric oxide (NO)-releasing alkyl chain modified poly(amidoamine) (PAMAM) dendrimers of various sizes (i.e., generations). Generation 1 (G1) through generation 4 (G4) dendrimers were modified with either short (i.e., butyl) or medium (i.e., hexyl) alkyl chains via a ring-opening reaction. The resulting secondary amines were subsequently modified with N-diazeniumdiolate NO donors to establish NO payloads of similar to 1.0 mu mol/mg. The bactericidal efficacy of these dendrimers was evaluated against Gram-negative and Gram-positive biofilms, including antibiotic-resistant strains. The anti-biofilm action of the dendrimer biocides was found to be dependent on dendrimer generation, bacterial Gram class, and alkyl chain length, with the most effective biofilm eradication occurring when antibacterial agents were capable of efficient biofilm infiltration. The addition of NO release markedly enhanced anti-biofilm activity of dendrimers incapable of effective biofilm penetration.