Surface localisation of photosensitisers on intraocular lens biomaterials for prevention of infectious endophthalmitis and retinal protection

Abstract

Cataract surgery is one of the most commonly-practiced surgical procedures in Western medicine, and, while complications are rare, the most serious is infectious postoperative endophthalmitis. Bacteria may adhere to the implanted intraocular lens (IOL) and subsequent biofilm formation can lead to a chronic, difficult to treat infection. To date, no method to reduce the incidence of infectious endophthalmitis through bacterial elimination, while retaining optical transparency, has been reported. In this study we report a method to optimise the localisation of a cationic porphyrin at the surface of suitable acrylate copolymers, which is the first point of contact with potential pathogens. The porphyrin catalytically generates short-lived singlet oxygen, in the presence of visible light, which kills adherent bacteria indiscriminately. By restricting the photosensitiser to the surface of the biomaterial, reduction in optical transparency is minimised without affecting efficacy of singlet oxygen production. Hydrogel IOL biomaterials incorporating either methacrylic acid (MAA) or methyl methacrylate (MMA) co-monomers allow tuning of the hydrophobic and anionic properties to optimise the localisation of porphyrin. Physiochemical and antimicrobial properties of the materials have been characterised, giving candidate materials with self-generating, persistent anti-infective character against Gram-positive and Gram-negative organisms. Importantly, incorporation of porphyrin can also serve to protect the retina by filtering damaging shortwave visible light, due to the Soret absorption (λmax 430 nm).

Fabrication of nonfouling, bactericidal, and bacteria corpse release multifunctional surface through surface-initiated RAFT polymerization

“…Infections after IOL implantation affect more than 30% of patients, which lead to the major visual loss and result in up to 18% blindness. 6,7 The grampositive coagulase-negative micrococcus Staphylococcus epidermidis is the most frequently cultured microorganism; however, Staphylococcus aureus and anaerobic species have also been implicated.…”

Bottom-up fabrication of zwitterionic polymer brushes on intraocular lens for improved biocompatibility

“…S. aureus is one of the critical pathogenic bacteria in infectious endophthalmitis after IOL implantation, causing much poor prognosis. 30 Herein, S. aureus was exposed to pristine or PMPC brush-modified silicone IOL material and stained by LIVE/DEAD BacLight bacterial viability kit. The distribution of the attached viable bacteria on the pristine or PMPC brush-functionalized IOL materials was observed by fluorescence microscopy, as shown in Figure 6.…”

Quantification of singlet oxygen generation from photodynamic hydrogels

“…The likely reason for the observed differences between treated and untreated hydrogels is the formation of a more dense surface layer on the surface of TMPyP-incorporated hydrogels, which reduces ingress of ADPA. TMPyP is known to be highly surface localised on hydrogels of this type [4]. In the case of low MAA content, the reduced availability of electrostatic binding sites decreases the density of TMPyP on the surface, therefore allowing a greater uptake of ADPA than the other materials studied.…”

“…Acrylate hydrogels were fabricated as previously described [4] via free radical-initiated polymerisation of the co-monomers. Tables 1 and 2 describe the relative quantities of co-monomers in each hydrogel copolymer, and the corresponding sample code for each.…”

“…Ingress of the probe into the materials was observed, with rates of up to 3.83 x 10 The high reactivity of photosensitiser-generated singlet oxygen ( 1 O2) has led to its exploitation for photodynamic therapy and photodynamic antimicrobial chemotherapy, and it therefore plays an important role in a number of clinical and antimicrobial treatments and areas of research [1][2][3]. Recently, we have prepared photosensitiserincorporated hydrogels for ocular applications [4]. On application of visible light to these hydrogels, 1 O2 is generated through the reaction of the excited state of the photosensitiser with molecular oxygen via what is often referred to as a type II pathway.…”