title: Sustained ocular delivery of ciprofloxacin using nanospheres and conventional contact lens materials.
abstract: OBJECTIVE
  To formulate conventional contact lenses that incorporate nanosphere-encapsulated antibiotic and demonstrate that the lenses provide for sustained antibacterial activity.
  
  
  METHODS
  A copolymer composed of pullulan and polycaprolactone (PCL) was used to synthesize core-shell nanospheres that encapsulated ciprofloxacin. Bactericidal activity of the nanosphere-encapsulated ciprofloxacin (nanosphere/cipro) was tested by using liquid cultures of either Staphylococcus aureus or Pseudomonas aeruginosa. Nanosphere/cipro was then incorporated into HEMA-based contact lenses that were tested for growth inhibition of S. aureus or P. aeruginosa in liquid cultures inoculated daily with fresh bacteria. Lens designs included thin or thick lenses incorporating nanosphere/cipro and ciprofloxacin-HCl-soaked Acuvue lenses (Acuvue; Johnson & Johnson Vision Care, Inc., Jacksonville, FL).
  
  
  RESULTS
  Less than 2 μg/mL of nanosphere/cipro effectively inhibited the proliferation of cultures inoculated with 10(7) or 10(8) bacteria/mL of S. aureus and P. aeruginosa, respectively. HEMA-based contact lenses polymerized with nanosphere/cipro were transparent, effectively inhibited the proliferation of greater than 10(7)/mL of bacteria added daily over 3 days of culture, and killed up to 5 × 10(9) total microbes in a single inoculation. A thicker lens design provided additional inhibition of bacterial growth for up to 96 hours.
  
  
  CONCLUSIONS
  Core-shell nanospheres loaded with an antibiotic can be incorporated into a conventional, transparent contact lens and provide for sustained and effective bactericidal activity and thereby provide a new drug delivery platform for widespread use in treating ocular disorders.
authors.affiliation: Department of Biological Sciences, University of Massachusetts Lowell, Lowell, Massachusetts 01854, USA.
authors.forename: Rahul
authors.initials: R
authors.lastname: Garhwal
authors.forename: Sally F
authors.initials: SF
authors.lastname: Shady
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Ellis
authors.forename: Jeanne Y
authors.initials: JY
authors.lastname: Ellis
authors.forename: Charles D
authors.initials: CD
authors.lastname: Leahy
authors.forename: Stephen P
authors.initials: SP
authors.lastname: McCarthy
authors.forename: Kathryn S
authors.initials: KS
authors.lastname: Crawford
authors.forename: Peter
authors.initials: P
authors.lastname: Gaines
mesh_terms: D000890:Anti-Infective Agents / Q000008:administration & dosage*; D002939:Ciprofloxacin / Q000008:administration & dosage*; D015169:Colony Count, Microbial; D003263:Contact Lenses, Hydrophilic; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D005936:Glucans / Q000737:chemistry; D006801:Humans; D008826:Microbial Sensitivity Tests; D018625:Microscopy, Atomic Force; D054118:Nanospheres; D011091:Polyesters / Q000737:chemistry; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000502:physiology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000502:physiology
chemical_list: D000890:Anti-Infective Agents; D003692:Delayed-Action Preparations; D005936:Glucans; D011091:Polyesters; C016240:polycaprolactone; D002939:Ciprofloxacin; C009109:pullulan