Drug-Delivering Contact Lenses: A Dream Worth Chasing?
BY LYNDON JONES, PHD, FCOPTOM, FAAO
For many years, practitioners have used hydrogel contact lenses as bandage lenses in cases of corneal disease and trauma. In many cases in which a bandage lens is required, the condition necessitates the simultaneous administration of antimicrobial or anti-inflammatory agents. A contact lens that could elute a topical drug over a prolonged period would have significant utility, as the therapeutic drugs often require dosing every few hours, which is highly inconvenient for patients.
The first documented report of using soft lenses as drug delivery devices was by Waltman and Kaufman in 1970, and the interest in this topic is evident by the fact that almost 200 papers have addressed this issue since that time. The drugs investigated have included anti-glaucoma medications, antibiotics, antiviral agents, epithelial growth factors and anti-inflammatory drugs.
Testing a Soak Method
The simplest of systems would be one in which soft lens materials were soaked in topical ophthalmic drugs and then placed on the ocular surface. Many studies over the past 40 years have investigated the potential for commercially available hydrogel lenses to act as drug delivery devices, with a recent study by Hui and colleagues (2008) being noteworthy as it included most current silicone hydrogel materials. They investigated the uptake and release characteristics of the antibiotic ciprofloxacin-HCl from three traditional hydrogel and six silicone hydrogel lenses. The lenses were soaked in 0.3% ciprofloxacin-HCl, and the release was measured when the lenses were subsequently placed in a buffered saline solution. The researchers reported that the release of drug varied from a low of 0.016 mg/lens for Night & Day (CIBA Vision) lenses to a maximum of 0.42 mg/lens for Acuvue 2 (Vistakon) lenses; the greatest amount of drug released from a silicone hydrogel lens was from PureVision (Bausch & Lomb), at 0.078 mg/lens.
While the majority of the lenses were able to release enough drug to achieve minimum inhibitory concentrations for most ocular pathogens, all materials released the drug too quickly to be effective as drug delivery devices, with the majority of the drug released within the first 15 minutes.
Other Uptake Methods
It is clear that alternative methods to encapsulate the drug of choice into the hydrogel are required, such that the release can be sustained over a prolonged period of time. One approach is to develop "particle-laden" lenses in which the drug is encapsulated in slow-releasing "nanoparticles," which are then dispersed throughout the lens material (Gulsen and Chauhan, 2004; Xinming et al, 2008). The size and dispersion of these particles is obviously critical, as particles that are too large or densely populated would impact the optical properties of the material (Danion et al, 2007).
Gulsen and Chauhan as well as de Campos et al (2004) and additional work by Gulsen and Chauhan (2005) have demonstrated that these approaches are able to produce hydrogel materials that deliver drugs for several days and show much promise in the elusive search for a drug-delivering lens that can deliver appropriate quantities of drugs for an extended period of time.
A further approach is to develop materials that have highly specific cavities within the materials (so-called "molecular imprinting" methods, Xinming et al, 2008) that can absorb high quantities of the drug of choice and release it over a prolonged period. This approach also provides delivery times that are substantially improved over that seen with commercial soft lenses (Hiratani et al, 2005; Alvarez-Lorenzo et al, 2006; Ali et al, 2007; Ali and Byrne, 2009; Hiratani et al, 2005).
Enhancing Lens Comfort
While most attention has been paid to the delivery of therapeutic agents such as antibiotics and steroids, the most pressing issue associated with contact lens wear continues to be end-of-day discomfort and dryness, which still continues to plague the contact lens industry. A delivery system that can enhance lens comfort would be widely accepted by practitioners and patients alike.
Winterton and colleagues (2007) from CIBA Vision describe the slow release of polyvinyl alcohol (PVA) from the nelfilcon A-based Focus Dailies family of lenses and indicate that, by careful design, "comfort-enhancing" non-therapeutic polymers can elute from a lens over a substantial period. It is possible that this process could also be used to deliver other agents of interest by "tethering" a drug to the slow-release polymer. Such an approach may be employed in future drug-delivering materials.
Poor surface wetting of contact lenses is often implicated in poor lens comfort. One interesting study by Papas and colleagues (2007) demonstrated the impact that a "new" contact lens has on end-of-day comfort. Subjects wore new daily disposable lenses on two consecutive days, and on one of these days the subjects applied a new lens mid-way through the day. Unfortunately, the end-of-day comfort reported on both days was identical, suggesting that it is the local ocular environment rather than the surface of the lens that in many cases is involved in end-of-day comfort issues.
The recent acknowledgement that dry eye includes an inflammatory component (International Dry Eye Workshop, 2007) opens up the opportunity for lenses that elute drugs that could potentially enhance lens comfort by reducing any low grade "inflammation" that may occur when contact lenses are worn. While such an approach involving the slow-release of steroidal agents may be problematic because of the risk of steroid-induced IOP increases or cataracts, it is well established that nonsteroidal anti-inflammatory drugs such as Voltaren (0.1% diclofenac sodium; Novartis), Nevanac (0.1% nepafenac; Alcon) and Acular LS (0.4% ketorolac tromethamine; Allergan) are highly beneficial in managing pain following abrasions and refractive and strabismus surgery (Sher et al, 1993; Donnenfeld et al, 1995; Schalnus, 2003; Durrie et al, 2007).
Hydrogel lenses that could deliver low quantities of these agents or other anti-inflammatory drugs would be interesting to study in terms of their ability to provide enhanced comfort, particularly at the end of the day. Recent papers (Chen et al, 2006; Andrade-Vivero et al, 2007; Geever et al, 2008; dos Santos et al, 2009) have looked at such delivery systems in the laboratory and they appear to show much promise, but clinical studies have yet to be reported.
Other agents worthy of study include the slow delivery of drugs such as cyclosporine, which could be useful in managing severe dry eye, and anti-allergy drugs. Allergy is a growing problem worldwide, and effective release of topical antihistamines and mast cell stabilizers would be a tremendous addition to the management of allergic eye disease. These are also under investigation (Venkatesh et al, 2007), and clinical studies will undoubtedly be undertaken in the near future.
Breakthroughs to Come
It is clear that drug-delivering hydrogel contact lenses are a focus for many research groups; the technologies involved will almost inevitably become a clinical reality in the contact lens arena within the next few years, both in the management of ocular surface disease and in the never-ending search for enhanced lens comfort.
Once developed, practitioners will need to consider the costs associated with fitting these products, develop guidelines on the follow-up required and ensure that the lenses are replaced at a frequency that ensures optimal performance — all of which will prove interesting practice-management issues as these technologies become available. CLS
For references, please visit www.clspectrum.com/references.asp and click on document #160.
Dr. Jones is the associate director of the Centre for Contact Lens Research and a professor at the School of Optometry at the University of Waterloo, Ontario, Canada. He has received research funding from Alcon, AMO, B&L, CIBA Vision, CooperVision, Johnson & Johnson and Menicon.