title: Optimization of ceragenins for prevention of bacterial colonization of hydrogel contact lenses.
abstract: OBJECTIVE
  We provided contact lens hydrogels with an antibacterial innate immune function using nonpeptide mimics of endogenous antimicrobial peptides.
  
  
  METHODS
  Antimicrobial peptide mimics, ceragenins, were prepared for either covalent attachment to hydrogels or for controlled elution from lenses. The lipophilicity of the ceragenins was varied incrementally to provide differing levels of association with hydrophobic domains in lenses. Ceragenin-containing lenses were challenged repeatedly with Staphylococcus aureus or Pseudomonas aeruginosa in nutrient media. Bacterial growth and biofilm formation on lenses were quantified.
  
  
  RESULTS
  A ceragenin covalently fixed in lenses effectively inhibited S. aureus biofilm formation on lenses in 10% tryptic soy broth (approximately 3-log reduction), but did not reduce biofilm formation in 100% tryptic soy broth. Ceragenins designed to elute from lenses were incorporated at 1% relative to the dry weight of the lenses. The ceragenin with the optimal lipid content, CSA-138, prevented bacterial colonization of lenses for 15 days with P. aeruginosa and for 30 days with S. aureus (daily exchange of growth media and reinoculation with 10⁶ CFU). Measurement of CSA-138 elution showed that concentrations of the ceragenin never exceeded 5 μg/mL in a 24-hour period and that after 4 days of elution, concentrations dropped to <0.5 μg/mL, while maintaining antibacterial activity.
  
  
  CONCLUSIONS
  Ceragenin CSA-138 appears well suited for providing an innate immune-like function to abiotic hydrogel contact lenses for extended periods of time. Elution of even low concentrations of CSA-138 (<0.5 μg) is sufficient to eliminate inocula of 10⁶ CFU of S. aureus and P. aeruginosa.
authors: Department of Chemistry and Biochemistry, Brigham Young University, Provo, Utah.
authors: Xiaobo
authors: X
authors: Gu
authors: Jacob D
authors: JD
authors: Jennings
authors: Jason
authors: J
authors: Snarr
authors: Vinod
authors: V
authors: Chaudhary
authors: Jacob E
authors: JE
authors: Pollard
authors: Paul B
authors: PB
authors: Savage
mesh_terms: D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects / Q000254:growth & development; D003263:Contact Lenses, Hydrophilic / Q000382:microbiology*; D015818:Eye Infections, Bacterial / Q000517:prevention & control*; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D008826:Microbial Sensitivity Tests; D011552:Pseudomonas Infections / Q000517:prevention & control; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D013203:Staphylococcal Infections / Q000517:prevention & control; D013211:Staphylococcus aureus / Q000187:drug effects; D013256:Steroids / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000890:Anti-Infective Agents; D013256:Steroids; C521528:ceragenin CSA-13; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate
keywords: antimicrobial peptide mimic; bacterial biofilm; bacterial infection