Fimbrolide-Coated Antimicrobial Lenses: Their In Vitro and In Vivo Effects

Zhu, Hua; Kumar, Ajay; Ozkan, Jerome; Bandara, Rani; Ding, Aidong; Perera, Indrani; Steinberg, Peter D.; Kumar, Naresh; Lao, William; Griesser, Stefani S.; Britcher, Leanne; Griesser, Hans J.; Willcox, Mark

doi:10.1097/opx.0b013e31816bea0f

Cited by 76 publications

(47 citation statements)

References 37 publications

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“…10,28 The incidence of fungal or amoebal keratitis during lens wear still remains much lower than for bacterial keratitis 1,4 but these continue to be difficult infections to diagnose and manage. 29,30 Strategies that have been designed to prevent microbial colonization of contact lenses include incorporation of nonsteroidal anti-inflammatory drugs (NSAID), 31,32 phosphorylcholine, 33 fimbrolides, 34 silver, 35 selenium, 36 antimicrobial cationic peptides (AMP), 37,38 or high density poly (ethylene oxide) dialdehyde (PEO(ALD) 2 ). 39 However, disadvantages of these technologies are that NSAIDs and silver need to be released from lenses to retain activity, and so might lose activity during use; PEO(ALD) 2 and phosphorylcholine coatings are passive anti-adhesive agents (i.e., do not contain inherent antimicrobial activity).…”

Section: Resultsmentioning

confidence: 99%

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Broad Spectrum Antimicrobial Activity of Melimine Covalently Bound to Contact Lenses

Dutta

Cole

Kumar

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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113

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PURPOSE. To develop a stable antimicrobial contact lens, which is effective against the International Organization for Standardization (ISO) panel microorganisms, Acanthamoeba castellanii and drug resistant strains of Pseudomonas aeruginosa and Staphylococcus aureus. METHODS.Melimine was covalently incorporated into etafilcon A lenses. The amount of peptide present on the lens surface was quantified using amino acid analysis. After coating, the heat stability (1218C), lens surface hydrophobicity (by captive bubble), and in vitro cytotoxicity to mouse L929 cells of the lenses were investigated. Antimicrobial activity against the micro-organisms was evaluated by viable plate count and fluorescence microscopy, measuring the proportion of cell death compared with control lenses with no melimine. RESULTS.The most effective concentration was determined to be 152 6 44 lg lens À1 melimine on the lens surface. After coating, lenses were relatively hydrophilic and were nontoxic to mammalian cells. The activity remained high after autoclaving (e.g., 3.1, 3.9, 1.2, and 1.0 log inhibition against P. aeruginosa, S. aureus, A. castellanii, and Fusarium solani, respectively). Fluorescence microscopy confirmed significantly reduced (P < 0.001) adhesion of viable bacteria to melimine contact lenses. Viable count confirmed that lenses were active against all the bacteria and fungi from the ISO panel, Acanthamoeba and gave at least 2 log inhibition against all the multidrug resistant S. aureus and P. aeruginosa strains.CONCLUSIONS. Melimine may offer excellent potential for development as a broad spectrum antimicrobial coating for contact lenses, showing activity against all the bacterial and fungal ISO panel microorganisms, Acanthamoeba, and antibiotic resistant strains of P. aeruginosa and S. aureus. (Invest Ophthalmol Vis Sci.

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Section: Resultsmentioning

confidence: 99%

“…This activity was much higher than that previously reported for fimbrolide-coated contact lenses (70% inhibition) against Acanthamoeba trophozoites. 34 Development of bacterial resistance against conventional antibiotics is a major problem. Resistance increases the risk of treatment failure with potentially serious consequences.…”

Section: Discussionmentioning

confidence: 99%

Broad Spectrum Antimicrobial Activity of Melimine Covalently Bound to Contact Lenses

Dutta

Cole

Kumar

et al. 2013

Invest. Ophthalmol. Vis. Sci.

Self Cite

113

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“…While this approach limits environmental contamination, it has not been successfully pursued. The techniques have been used effectively against bacterial biofouling on biomedical devices (Hume et al 2004;Zhu et al 2008) and this is an area of technical promise with the move towards legislation restricting antifouling technologies to non-release mechanisms.…”

Section: Non-leaching Biocidesmentioning

confidence: 99%

The impact and control of biofouling in marine aquaculture: a review

et al. 2012

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Biofouling in marine aquaculture is a specific problem where both the target culture species and/or infrastructure are exposed to a diverse array of fouling organisms, with significant production impacts. In shellfish aquaculture the key impact is the direct fouling of stock causing physical damage, mechanical interference, biological competition and environmental modification, while infrastructure is also impacted. In contrast, the key impact in finfish aquaculture is the fouling of infrastructure which restricts water exchange, increases disease risk and causes deformation of cages and structures. Consequently, the economic costs associated with biofouling control are substantial. Conservative estimates are consistently between 5-10% of production costs (equivalent to US$ 1.5 to 3 billion yr 71 ), illustrating the need for effective mitigation methods and technologies. The control of biofouling in aquaculture is achieved through the avoidance of natural recruitment, physical removal and the use of antifoulants. However, the continued rise and expansion of the aquaculture industry and the increasingly stringent legislation for biocides in food production necessitates the development of innovative antifouling strategies. These must meet environmental, societal, and economic benchmarks while effectively preventing the settlement and growth of resilient multi-species consortia of biofouling organisms.

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“…An arbitrary value of 0.7 was used as an indicator in this assay for assessing the "acceptable level" of cell inhibition [29,30]. A comparison between PU and PUNCs fabricated either as films or coatings is shown in Figure 3.…”

Section: Cell Growth Inhibition (Cgi)mentioning

confidence: 99%

“…CGI was expressed as a ratio of the number of cells in test material to the number of cells in PU control. A ratio of 0.7 or higher was considered an 'acceptable level' of cell growth inhibition within this assay [29,30]. Materials were performed in triplicates and the assay was repeated in triplicates.…”

Section: Cell Growth Inhibition (Cgi) Assaymentioning

confidence: 99%

Polyurethane Organosilicate Nanocomposites as Blood Compatible Coatings

et al. 2012

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Polymer clay nanocomposites (NCs) show remarkable potential in the field of drug delivery due to their enhanced barrier properties. It is hypothesised that well dispersed clay particles within the polymer matrix create a tortuous pathway for diffusing therapeutic molecules, thereby resulting in more sustained release of the drug. As coatings for medical devices, these materials can simultaneously modulate drug release and improve the mechanical performance of an existing polymer system without introducing additional materials with new chemistries that can lead to regulatory concerns. In this study, polyurethane organosilicate nanocomposites (PUNCs) coated onto stainless steel wires were evaluated for their feasibility as blood compatible coatings and as drug delivery systems. Heparin was selected as the model drug to examine the impact of silicate loading and modifier chain length in modulating release. Findings revealed that better dispersion was achieved from samples with lower clay loadings and longer alkyl chains. The blood compatibility of PUNCs as assessed by thrombin generation assays showed that the addition of silicate particles did not significantly decrease the thrombin generation lag time (TGT, p = 0.659) or the peak thrombin (p = 0.999) of polyurethane (PU). PUNC coatings fabricated in this research were not cytotoxic as examined by the cell growth inhibition OPEN ACCESSCoatings 2012, 2 46 assay and were uniformly intact, but had slightly higher growth inhibition compared to PU possibly due to the presence of organic modifiers (OM). The addition of heparin into PUNCs prolonged the TGT, indicating that heparin was still active after the coating process. Cumulative heparin release profiles showed that the majority of heparin released was from loosely attached residues on the surface of coils. The addition of heparin further prolonged the TGT as compared to coatings without added heparin, but a slight decrease in heparin activity was observed in the NCs. This was thought to be from competitive interactions between clay-heparin that influenced the formation of the ternary complex between heparin, ATIII thrombin. In summary, the feasibility of using PUNC as drug delivery coatings was shown by the good uniformity in the coating, absence of by-products from the coating process, and the release of active molecules without significantly interfering with their activity.

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Fimbrolide-Coated Antimicrobial Lenses: Their In Vitro and In Vivo Effects

Abstract: Fimbrolide-coated lenses show promise as an antibacterial and anti-acanthamoebal coating on contact lenses and appear to be safe when worn on the eye in an animal model.

Cited by 76 publications

References 37 publications

Broad Spectrum Antimicrobial Activity of Melimine Covalently Bound to Contact Lenses

Broad Spectrum Antimicrobial Activity of Melimine Covalently Bound to Contact Lenses

The impact and control of biofouling in marine aquaculture: a review

Polyurethane Organosilicate Nanocomposites as Blood Compatible Coatings

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