title: Anti-infective photodynamic biomaterials for the prevention of intraocular lens-associated infectious endophthalmitis.
abstract: Bacterial attachment onto intraocular lenses (IOLs) during cataract extraction and IOL implantation is a prominent aetiological factor in the pathogenesis of infectious endophthalmitis. Photodynamic therapy (PDT) and photodynamic antimicrobial chemotherapy (PACT) have shown that photosensitizers are effective treatments for cancer, and in the photoinactivation of bacteria, viruses, fungi and parasites, in the presence of light. To date, no method of localizing the photocytotoxic effect of a photosensitizer at a biomaterial surface has been demonstrated. Here we show a method for concentrating this effect at a material surface to prevent bacterial colonization by attaching a porphyrin photosensitizer at, or near to, that surface, and demonstrate the principle using IOL biomaterials. Anionic hydrogel copolymers were shown to permanently bind a cationic porphyrin through electrostatic interactions as a thin surface layer. The mechanical and thermal properties of the materials showed that the porphyrin acts as a surface cross-linking agent, and renders surfaces more hydrophilic. Importantly, Staphylococcus epidermidis adherence was reduced by up to 99.02+/-0.42% relative to the control in intense light conditions and 91.76+/-5.99% in the dark. The ability to concentrate the photocytotoxic effect at a surface, together with a significant dark effect, provides a platform for a range of light-activated anti-infective biomaterial technologies.
authors.affiliation: McClay Research Centre, School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, UK.
authors.forename: Carole
authors.initials: C
authors.lastname: Parsons
authors.forename: Colin P
authors.initials: CP
authors.lastname: McCoy
authors.forename: Sean P
authors.initials: SP
authors.lastname: Gorman
authors.forename: David S
authors.initials: DS
authors.lastname: Jones
authors.forename: Steven E J
authors.initials: SE
authors.lastname: Bell
authors.forename: Clare
authors.initials: C
authors.lastname: Brady
authors.forename: Seana M
authors.initials: SM
authors.lastname: McGlinchey
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D001422:Bacterial Adhesion / Q000187:drug effects; D001672:Biocompatible Materials / Q000494:pharmacology*; D009877:Endophthalmitis / Q000382:microbiology* / Q000517:prevention & control*; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D007910:Lenses, Intraocular / Q000382:microbiology*; D055595:Mechanical Phenomena / Q000187:drug effects; D008689:Methacrylates; D008826:Microbial Sensitivity Tests; D010778:Photochemotherapy; D011166:Porphyrins / Q000737:chemistry; D013212:Staphylococcus epidermidis / Q000187:drug effects; D013718:Tensile Strength; D044366:Transition Temperature
chemical_list: D000890:Anti-Infective Agents; D001672:Biocompatible Materials; D008689:Methacrylates; D011166:Porphyrins; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; C005044:hydroxyethyl methacrylate