Alex Hui, OD, is a PhD Candidate at the Centre for Contact Lens Research in the School of Optometry and Vision Science, University of Waterloo. His research focus is on the development of novel contact lens materials for drug delivery.Drug delivery to the eye mainly consists of four different routes of administration: injections, surgically implanted devices, systemic administration and most commonly, topical administration.1 Each of these routes of delivery has its own advantages and disadvantages. For example, injections are able to achieve a large, targeted dose of a pharmaceutical in a target area, but require repeated injections for ongoing effectiveness. This is most evident in the treatment of wet macular degeneration with current anti-vascular endothelial growth factor(VEGF) agents, in which patients can expect intravitreal injections as frequently as every month. By far, the most common method of treating the eye is through topical therapy in the form of eye drops.2 Eye drops are able to achieve a high concentration of drug within the targeted ocular tissue, but unfortunately rely on patient compliance and frequent dosing to reach therapeutic concentration targets. Even with the aid of frequent monitoring and reminders, it is expected that patients on chronic ocular treatment for such things as glaucoma are compliant less than 50% of the time.3 Thus, there is clearly a need for alternative strategies to treating the anterior surface of the eye if compliance issues are to be dealt with effectively
Contact Lenses?
From this paradigm of challenges to ocular drug delivery emerges the concept of contact lenses as drug delivery devices. This idea is not new – there are papers published from the 1960s, soon after the introduction of soft contact lenses, postulating the application of contact lenses in such a way.4 Unfortunately, the contact lens technology at the time was still fairly primitive.
The challenges at that time included material development to combat a host of biocompatibility issues such as deposits, disinfection, comfort and oxygen permeability, not to mention the quality assurance and quality control procedures that still needed to be developed to reliably reproduce lenses from batch to batch to merely control refractive error.
Contact lenses as drug reservoirs thus were placed (rightly) on the back burner of contact lens research. It was not until the late 1990s when much of the contact lens developments were sufficiently advanced for alternative applications of contact lenses to begin to be explored.
The introduction of silicone hydrogels was seen as a great evolutionary leap forward in contact lens materials and wear – no longer was hypoxia of the eye a common complication, opening the door for the potential of safe overnight wear and expanding the usefulness of a potential drug delivery contact lens.5 There was suddenly renewed interest in this concept – could contemporary, commercially available materials not only correct refractive error, but also deliver therapeutically relevant amounts of drugs?
Early Challenges
Unfortunately, they could not. Surveying commercially available materials for potential drug delivery was mainly a disappointing avenue, which was not necessarily unexpected as the materials were not designed for this purpose. The lenses surveyed would generally demonstrate ability to uptake and release drugs into solutions and reach therapeutically relevant concentrations, but would only deliver drugs for a few short hours in a rapid burst release, not a steady, consistent dosage over a long period of time.
Antibiotics, 6 anti-inflammatories,7 anti-allergy8 and non-steroidal anti-inflammatories (NSAIDs)8 all showed similar patterns of release. New materials were thus clearly needed if contact lenses were to be used as drug delivery devices – specifically tailored for the delivery of pharmaceuticals for a long period of time.
Recent Successes
The field of contact lens drug delivery has since begun a rapid pace of exploration and study. Researchers in the field have identified different material development strategies to extend the release time of pharmaceuticals from these lenses.
First, the base material can be modified right at the polymerization process. In the technique of molecular imprinting, high affinity “cavities” or molecular memory is created within the material by polymerizing in the presence of a template.9 These “cavities” serve to retard the diffusion of the loaded drug, which closely resembles (or was used as) the template.
Second, the method of drug loading into the lens can also be varied to affect release times. The drug can be encapsulated at a high concentration within a thin film, and the traditional contact lens material polymerized above and below it; the film serves as a drug reservoir that must diffuse through the contact lens material before it can be released.10 The drug can also be loaded and attached to the contact lens surface using microemulsions11 or cyclodextrins12, which serve to dissolve and encapsulate the drug, providing another barrier to drug diffusion and transport.
Third and finally, the surfaces of commercially available lenses can be modified so that they prevent the rapid diffusion and loss of the drug. Recent studies have investigated the use of coatings or diffusion barriers and has demonstrated success in decreasing the release time of glaucoma13, anaesthetic14 and anti-inflammatory drugs15 from contact lenses.
A rapid pace of development
The field has continued to grow and expand. Simply observing the number of papers published and cited shows a clear and rapid upward trend in contact lenses and drug delivery. The greatest development has been in the techniques used to simulate or model drug delivery from such combination devices when they are actually placed on the ocular surface. Devices have been created to simulate the flow of tears through these devices16.
In vivo animal studies have also begun. Two recent papers have demonstrated superiority of these contact lens drug delivery devices compared to eye drops for the treatment of allergy in rabbits17 and glaucoma in spontaneously glaucomatous dogs13. Human trials for an anti allergy contact lens have already completed Phase I and Phase II trials, suggesting that a release of a combination drug delivery device may be imminent18.
Conclusions
It is clear that contact lenses for the delivery of pharmaceuticals are an ever evolving discipline and an area of great interest for researchers. As the materials become more and more advanced and developed, the reality of a commercially available contact lens devices seems to be right around the corner.
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3. Stone JL, Robin AL, Novack GD, Covert DW, Cagle GD. An objective evaluation of eyedrop instillation in patients with glaucoma. Arch Ophthalmol 2009;127:732-6.
4. Sedlácek J. Possibility of the application of ophthalmic drugs with the use of gel contact lenses. Ceskoslovenska oftalmologie 1965;21:509-12.
5. Grobe G, Kunzler J, Seelye D, Salamone J. Silicone hydrogels for contact lens applications. Polymeric Materials Science and Engineering 1999;80:108 – 9.
6. Hui A, Boone A, Jones L. Uptake and release of ciprofloxacin-HCl from conventional and silicone hydrogel contact lens materials. Eye and Contact Lens 2008;34:266.
7. Boone A, Hui A, Jones L. Uptake and release of dexamethasone phosphate from silicone hydrogel and group I, II, and IV hydrogel contact lenses. Eye and Contact Lens 2009;35:260.
8. Karlgard CC, Wong NS, Jones LW, Moresoli C. In vitro uptake and release studies of ocular pharmaceutical agents by silicon-containing and p-HEMA hydrogel contact lens materials. Int J Pharm 2003;257:141-51.
9. Alvarez-Lorenzo C, Concheiro A. Molecularly imprinted polymers for drug delivery. J Chromatogr B Analyt Technol Biomed Life Sci 2004;804:231-45.
10. Ciolino JB, Hoare TR, Iwata NG, Behlau I, Dohlman CH, Langer R, Kohane DS. A drug-eluting contact lens. Investigative Ophthalmol Vis Sci 2009;50:3346.
11. Gulsen D, Chauhan A. Dispersion of microemulsion drops in HEMA hydrogel: A potential ophthalmic drug delivery vehicle. International J Pharma 2005;292:95.
12. Rosa dos Santos JF, Alvarez-Lorenzo C, Silva M, Balsa L, Couceiro J, Torres-Labandeira JJ, Concheiro A. Soft contact lenses functionalized with pendant cyclodextrins for controlled drug delivery. Biomaterials 2009;30:1348.
13. Peng CC, Ben-Shlomo A, MacKay EO, Plummer CE, Chauhan A. Drug delivery by contact lens in spontaneously glaucomatous dogs. Current Eye Research 2012;37:204-11.
14. Peng CC, Burke MT, Chauhan A. Transport of topical anesthetics in vitamin e loaded silicone hydrogel contact lenses. Langmuir 2012;28:1478-87.
15. Peng CC, Kim J, Chauhan A. Extended delivery of hydrophilic drugs from silicone-hydrogel contact lenses containing vitamin E diffusion barriers. Biomaterials 2010;31:4032-47.
16. Ali M, Horikawa S, Venkatesh S, Saha J, Hong JW, Byrne ME. Zero-order therapeutic release from imprinted hydrogel contact lenses within in vitro physiological ocular tear flow. J Controlled Release 2007;124:154.
17. Tieppo A, White CJ, Paine AC, Voyles ML, McBride MK, Byrne ME. Sustained in vivo release from imprinted therapeutic contact lenses. J Controlled Release 2012;157:391-7.
18. ClinicalTrials.gov. Safety Study of a Contact Lens With Ketotifen in Healthy, Normal Volunteers. National Library of Medicine 2011 [updated 2011 June 23, 2011. Available at: http://clinicaltrials.gov/ct2/show/NCT00569777?term=ketotifen+contact+lens&rank=2. Accessed: 2011 July 20];
