title: Anti-Biofilm Efficacy of Dual-Action Nitric Oxide-Releasing Alkyl Chain Modified Poly(amidoamine) Dendrimers.
abstract: 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 ∼1.0 μmol/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.
authors: Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
authors: Brittany V
authors: BV
authors: Worley
authors: Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
authors: Kelci M
authors: KM
authors: Schilly
authors: Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
authors: Mark H
authors: MH
authors: Schoenfisch
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D018441:Biofilms / Q000187:drug effects*; D002460:Cell Line; D050091:Dendrimers / Q000737:chemistry*; D051379:Mice; D008826:Microbial Sensitivity Tests; D009569:Nitric Oxide / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology; D011073:Polyamines / Q000009:adverse effects / Q000737:chemistry*; D013211:Staphylococcus aureus / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D050091:Dendrimers; C531249:Poly(amidoamine); D011073:Polyamines; D009569:Nitric Oxide
keywords: antibacterial; biofilm; methicillin-resistant Staphylococcus aureus (MRSA); nitric oxide; poly(amidoamine) (PAMAM) dendrimer