Developing Antimicrobial Surfaces for Silicone Hydrogels

During the past few decades, advances in contact lens and lens care technologies have further contributed to the safety and efficacy of contact lens wear, making contact lenses an option for more patients than ever before. In fact, it is estimated that there are now over 110 million contact lens wearers worldwide. However, despite the improved oxygen transmissibility of silicone hydrogel lenses and the effectiveness of new lens care solutions, some patients still experience microbial contamination of their contact lenses.

When microbial contamination occurs, colonization is initially caused by bacterial adhesion to the lens surface. [1] Preventing bacterial adhesion would limit biofilm formation, which could help prevent infection and inflammation.

One potential method for preventing bacterial adhesion is the use of antimicrobial agents, which have been used in the medical field for decades. Antimicrobial agents have been used for a wide range of products including orthopedic implants, urinary catheters and wound dressings, to name a few. [2-5] Currently, researchers are exploring the option of using antimicrobial surfaces and materials for contact lenses to further improve their safety.

A wide variety of antimicrobial technologies could potentially be employed for use with a contact lens. Some may be applied to the surface of the lens material, while others may be infused directly into the lens polymer.  Regardless of how it is created, the goal of an antimicrobial lens is to reduce or eliminate adverse events caused by infective agents. An ideal “antimicrobial lens” would be, among other things, non-toxic to the human cornea and other tissues, would provide broad-spectrum antimicrobial activity, and would have minimal impact on the normal ocular flora.

Possible Antimicrobial Technologies for Use in Contact Lenses

Researchers are currently investigating several antimicrobial surface technologies for use in the medical field. For example, silver is currently used as the active agent on the surface of many antimicrobial medical devices. When used on the surface, silver slows the adherence and colonization of microorganisms by inhibiting DNA and RNA replication, disrupting the cell membrane, and interfering with cell respiration. Silver is also currently being used in the contact lens industry. In fact, the FDA has approved a silver-impregnated contact lens case (CIBA VISION) for use with AQuify Multi-Purpose Solution. [5] When an aqueous solution comes in contact with  the case,  silver ions are slowly released, which provides antibacterial properties that will kill bacteria on contact.
Polymeric quaternary ammonium compounds (polyquats) are another option. They are commonly used as disinfectants, preservatives, and algaecides for pools and hot tubs. Polyquats have also been used in contact lens solutions as disinfectants and preservatives. Their efficacy in contact lens solutions is primarily caused by chelation of bacterial components with the compound. More recently, these compounds have been used in dental fillings, catheters, and polymers used in contact lenses to reduce bacterial biofilm formation and adherence to the surfaces of the devices. [6-8]

Polymeric pyridinium compounds can be covalently bonded to surfaces and have been shown to have a broad spectrum of antimicrobial activity. Upon contact with bacteria, the long amphipathic polycationic chains penetrate the bacterial cell wall. In 2001, Tiller and colleagues studied coatings made from two polymeric pyridinium compounds.  They found that, in addition to having a broad spectrum of activity, the compounds did not leach from the material, so they were not depleted over time.9 Researchers have found that they can be applied to contact lens polymers.

Free radical-producing agents, such as selenium compounds and nitric oxide-releasing polymers, have been used for antimicrobial coatings as well. Selenium compounds can generate superoxide free radicals which can oxidize bacterial cells and prohibit cell growth. In 2006, Mathews and colleagues published the results of a study investigating silicone hydrogel contact lenses with covalently bonded selenium in a rabbit model. [10] These lenses demonstrated resistance to P. aeruginosa colonization in vitro. Additionally, after two months of extended wear, corneal health was not adversely affected by the selenium-coated silicone hydrogel contact lenses.

Nitric oxide-releasing polymers also have antimicrobial properties, which are the result of oxidative and nitrosative stress caused by reactive intermediates of nitric oxide. In 2005, Nablo and colleagues studied nitric oxide-releasing coatings for stainless steel orthopedic implants, and found that these coatings can inhibit the adhesion of P. aeruginosa, S. aureus, and S. epidermidis. [3]

Quorum-sensing compounds are another class of agents with potential for use in antimicrobial coatings.  The ability of microorganisms to communicate with each other and coordinate behavior is called quorum sensing. Subsequently, Quorum-sensing compounds inhibit bacteria by interfering with their signaling systems. Furanones (one example of quorum sensing compounds) are agents that occur naturally in red algae and prevent bacteria from colonizing on the algae’s surface. The antimicrobial effect of adsorbed synthetic furanones on medical device polymers has been studied. [4] Baveja and colleagues, have reported that a furanone-coated material significantly reduced S. epidermidis bacterial load on the polymer and slime production, while having no significant effect on the substrate’s material characteristics. The use of furanones to coat contact lenses has also been studied. In one study, contact lenses were soaked in synthetic furanone, but the study results were unclear. [11] In another study, Zhu and colleagues found that fimbrolide used in coating contact lenses  show promise as an antibacterial and anti-acanthamoebal coating and appear to be safe in an animal model. [12]

Anti-infectives, a different class of agents, also kill infectious organisms or prevent them from increasing in number and causing infection. Many antibacterial peptides are known to form pores in the lipid bilayers of microorganisms and cause a leakage of the organism’s cell contents. In 2008, Willcox and colleagues demonstrated antimicrobial activity of contact lenses with cationic peptide coatings made of synthetic melamine and incorporating regions of protamine and melitin on the lenses. [13] They found that, when tested against P. aeruginosa and S. aureus, the coatings inhibited bacterial colonization by 70% for both bacteria.  Ferreira et al. documented the use of antimicrobial peptide (cysteine-incorporating cecropin-melitin hybrid peptide) immobilized on a planar surface exhibited antimicrobial properties after more than three weeks of storage in phosphate-buffered saline. [14]

The human body has potent anti-infectives that naturally occur from neutrophils and macrophages. [15] Defensins, small peptides that are rich in cysteine, and one family of these naturally-occurring anti-infectives can inhibit bacteria, fungi, and viruses.  Defensins bind to the membranes of infecting organisms and increase permeability, decreasing the likelihood of resistance. Lactoferrin is another naturally-occurring anti-infective. It is found throughout the body in mucous membrane secretions, such as saliva, tears, nasal and bronchial secretions, hepatic bile, and pancreatic fluids, and is essential for immune response. In a 2002 study, Singh and colleagues demonstrated that lactoferrin blocks P. aeruginosa biofilm development. [16] It is believed that lactoferrin acts by stimulating “twitching” of the bacteria, which prevents them from adhering to surfaces.

Summary

Not surprisingly, researchers in the contact lens industry have shown significant interest in agents that would provide antimicrobial properties for surfaces of contact lenses because they could reduce or eliminate the adherence of microbes to contact lenses and lens cases. Reducing exposure to infectious microorganism could make contact lens wear possible for more patients and extended and continuous wear of contact lenses could improve convenience and increase acceptance of contact lenses as a vision care correction of choice.  Patients could experience an added measure of protection from microbial contamination without any extra effort on their part. An additional benefit is that bacterial resistance to many antimicrobial agents is unlikely because of their mechanisms of action.

Additional research is needed, and future needs include other aspects of antimicrobial technology, such as whether antimicrobial lenses are compatible with lens care and whether antimicrobial agents could cause an allergic response. It is also unknown whether these agents would have unintended effects such as the build-up of endotoxins. Another concern is the cost of manufacturing antimicrobial lenses. These issues need to be adequately studied, and the answers will aid in the development of contact lenses that incorporate antimicrobial or anti-infective technology.

References

• Willcox MD, Harmis N, Cowell B, Williams T, Holden BA. Bacterial interactions with contact lenses; effects of lens material, lens wear and microbial physiology. Biomaterials. 2001;22(24):3235-3247.
• Gabriel MM, Mayo MS, May LL, Ahearn DG. In vitro evaluation of the efficacy of a silver-coated catheter. Curr Microbiol. 1996;33:1-5.
• Nablo BJ, Rothrock AR, Schoenfisch MH. Nitric oxide-releasing sol-gels as antibacterial coatings for orthopedic implants. Biomaterials. 2005;26:917-924.
• Baveja JK, Willcox MDP, Hume EBH, Kumar N, Odell R, Poole-Warren LA. Furanones as potential anti-bacterial coatings on biomaterials. Biomaterials. 2004;25:5003-5012.
• Amos CF, George MD. Clinical and laboratory testing of a silver-impregnated lens case. Contact Lens Anterior Eye. 2006;29(5):247-255.
• Whiteford JA, Freeman WF. Methods and systems for preparing antimicrobial films and coatings. 2007. PCT WO2007/070801A2.
• Majumdar P, Lee E, Patel N, Stafslien SJ, Daniels J, Thorson CJ, Chisholm BJ. Medical device coatings based on polysiloxanes containing tethered quaternary ammonium salts. Polymer Preprints (American Chemical Society, Division of Polymer Chemistry). 2008;49(1):852-853.
• Morris CA, Gabriel MM, Qui Y, Winterton LC, Lally JM, Ash MK, Carney FP. Medical devices having antimicrobial coatings thereon. US7402318B2
• Tiller JC, Liao CJ, Lewis K, Klibanov AM. Designing surfaces that kill bacteria on contact. Proc Natl Acad Sci USA. 2001;98(11):5981-5985.
• Mathews SM, Spallholz JE, Grimson MJ, Dubielzig RR, Gray T, Reid TW. Prevention of bacterial colonization of contact lenses with covalently attached selenium and effects on the rabbit cornea. Cornea. 2006;25(7):806-814.
• George M, Pierce G, Gabriel MM, Morris C, Ahearn DG. Effects of quorum sensing molecules of Pseudomonas aeruginosa on organism growth, elastase B production, and primary adhesion to hydrogel contact lenses. Eye Contact Lens. 2005;31(2):54-61.
• Zhu H, Kumar A, Ozkan J, et al. Fimbrolide-coated antimicrobial lenses: Their in vitro and in vivo effects. Optometry and Vision Sciences. 2008;85(5):292-300.
• Willcox MDP, Hume EBH, Aliwarga Y, Kumar N, Cole N. A novel cationic-peptide coating for the prevention of microbial colonization on contact lenses. J Appl Microbiol. 2008;105:1817-1825.
• Ferreira L, Langer R, Loose CR, O’Shaughnessy WS, Zumbuehl A, Stephanopolous. Medical devices and coatings with non-leaching antimicrobial peptides. 2007. WO2007095393A2.
• McDermott AM. The role of antimicrobial peptides at the ocular surface. Ophthalmic Res 2008;41:60-75.
• Singh PK, Parsek MR, Greenberg EP, Welsh MJ. A component of innate immunity prevents bacterial biofilm development. Nature. 2002;417:552-555.