Effectiveness of Nitric Oxide for bacterial and fungal activity in contact lens systems

Jimmy K. Lee, MD

Presenter:

Jimmy K. Lee, MD1, Girish Vallerinteavide Mavelli, PhD2, Jyothishree Tholalu Jayadeva, BTech2, Shivaleela Keerthy, MS2, Mel Erlich, PhD2 and Mahantesh S. Navati, PhD2

Authors:

Affiliation:

1. Department of Ophthalmology and Visual Sciences, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York – 10461

2. NMB Therapeutics, Inc., Ullmann 1223, 1300 Morris Park Avenue, Bronx, New York – 10461

Purpose:

The widespread use of therapeutic and cosmetic contact lenses has increased the incidence of infectious keratitis. Despite attempts to improve cleaning regimens, microbes can establish resistant biofilms on the contact lenses and storage cases. Nitric oxide (NO), a small lipophilic molecule has been well studied as an antimicrobial agent with no known reports of antimicrobial resistance. In this study, we took advantage of this phenomenon to create a biodegradable nitric-oxide releasing powder: NOP20TM capable of sterilizing both planktonic and biofilm-associated microbes. This NO-releasing powder has the potential to be a novel contact-lens sterilization agent.

Methods:

NOP20TM is a novel nitric-oxide releasing powder(NMB Therapeutics, Bronx, New York). NO release rates were measured using a NO analyzer (Sievers 280i, Boulder, CO). Antimicrobial effects of NOP20TM on contact lenses infected with microbial strains Pseudomonas aeruginosa (ATCC® 9027TM) and Candida albicans (ATCC® MYA-2876TM) from American type culture collection (ATCC, Manassas, VA) was studied through colony forming unit (CFU) count assay.

Results:

The rate of NO release from NOP20TM was determined to be 35 nmoles/mg/min [Fig. 1]. It was characterized by an initial burst of NO up to 22000 ppb for 10 min followed by a slow and steady release. We also studied the antimicrobial efficacy of NOP20TM in sterilizing contact lens from microbial growth. We selected the time intervals of 8 and 12h as most contact lenses are stored in disinfectant solutions for these time points. NOP20TM completely inhibited the growth of both the microbial strains, P. aeruginosa and C. albicans at 8h and 12h treatment (p≤0.0001) [Fig. 2].

Conclusions:

Contact lenses remain the main culprit for corneal ulcers in the developed world. Although commercially available multipurpose solutions are effective in sterilizing most bacteria, P. aeruginosoa and C. albicans are difficult pathogens to culture and treat. In this study, we introduce a novel nitric-oxide releasing nanopowder, NOP20TM that dramatically reduced P. aeruginosoa and C. albicans growth on soft contact lenses.  In the future, its efficacy on another difficult pathogen, Acanthamoeba, will be investigated. This study suggests that nitric-oxide releasing nanopowders may be an important adjunct for reducing contact-lens related keratitis in the future.

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