When treating ocular conditions, topical medications can offer many advantages, including the ability to achieve high tissue concentrations and with limited systemic side effects. However, delivering an effective dose to ocular tissues can be a challenge. The bioavailability of most topical ophthalmic medications is surprisingly limited. The tears and lacrimal system efficiently wash drugs out of the eye before they can be absorbed, and competition with tissues other than intended targets can reduce available drug levels substantially. Even the corneal epithelium itself presents a formidable barrier to drug penetration.
With the high cost and regulatory burdens associated with new drug development rising rapidly, a variety of strategies and technologies have been developed to increase the effectiveness of existing drugs. The use of engineered drug delivery vehicles increases ophthalmic drug bioavailability and typically improves therapeutic effectiveness. For example, the propriety vehicle DuraSite (InSite Vision, Inc.) is used in the drugs AzaSite (azithromycin 1%, Merck) and Besivance (besifloxacin 0.6%, Bausch + Lomb) to prolong drug-ocular surface contact time, which results in enhanced penetration. DuraSite creates a polymeric mucoadhesive matrix depot, which forms a gel upon instillation into the eye. Xanthan gum, used in both TobraDex ST (tobramycin 0.3%/dexamethasone 0.1%, Alcon) and Moxeza (moxifloxacin 0.5%, Alcon), have a similar mechanism of action.
Why Contact Lenses?
Renowned Czech chemist, Otto Wichterle, Ph.D., invented the first hydrogel material. Quickly recognizing the potential for hydrogel materials to be manufactured into contact lenses, Dr. Wichterle produced the first soft lenses in his own kitchen using a spin casting apparatus that he devised.1 Soon afterwards––even before the first hydrogel lenses were commercially available—J. Sedlavek, a Czech ophthalmologist, explored the use of hydrogels to deliver drugs.2
The benefit of using soft bandage lenses in managing a variety of ocular diseases and conditions quickly became apparent.3,4 Numerous reports describing bandage lens applications to protect the cornea and facilitate healing were published in the ophthalmologic and optometric literature during the 1970s and 1980s.5 Some clinicians advocated the concurrent use of topical antibiotics with long-term bandage lens use to prevent infection.6 Bandage lenses soon became standard of care, replacing pressure patching in most situations.
Because of the affinity of hydrogel materials for water-soluble topical ophthalmic medications, the use of bandage contact lenses to deliver medications quickly gained favor. Early reports describe the use of soft lenses as depots to dispense glaucoma medications, anti-inflammatories and anti-infective agents.7,8
Conventional hydrogels are a mixture of hydrophobic plastics and water. Their relatively high water content and typically large pore structure make them an effective depot for many drugs. The addition of silicone to conventional hydrogel materials improves permeability and can enhance the delivery of certain medications.9,10
The relatively slow release of drugs from hydrogel and silicone hydrogel lenses increases ocular bioavailability well beyond what can be achieved with conventional eye drops. Drug-releasing contact lenses also prolong residence time, enhance the effectiveness of most pharmaceutical agents and generally aid with patient compliance. Slower drug release rates promote diminished systemic absorption, which limits the potential for associated side effects.11,12
An additional benefit of soft lenses is that most patients can easily apply them to the eye after appropriate training, and the lenses are designed to be comfortable and compatible with ocular tissues. Compared to having patients instill drops several times a day, using lenses to dispense ophthalmic drugs can be more convenient for long-term therapy. More consistent drug levels are also maintained in target tissues, which often equates to greater therapeutic efficacy.
Today’s Drug Delivery Technology
For a contact lens to be successfully used as a drug delivery vehicle, the drug cannot interfere with the essential characteristics of the lens. Added medications should not affect comfort, oxygen permeability, modulus, transparency or surface wettability of the lens. Also, the addition of a drug should not change lens-fitting characteristics or the prescription. Alteration of these critical properties can render the lens unwearable.
Traditionally, lenses were loaded with drugs––either by frequent instillation while the lens was worn or by presoaking the lens in the desired medication.7,8 In the former case, the lens served as a depot, absorbing the instilled medication and releasing it at a much slower rate as the drug sought equilibrium with the tears. Presoaking the lens was more efficient; less drug was lost upon instillation and there was a more even distribution. Results with either technique using commercially available lenses are quite variable, depending on drug chemistry, solubility, lens material, water content and numerous other factors.
A number of novel approaches have been used to optimize and extend drug delivery with contact lenses. Techniques to incorporate pharmaceutical agents directly into lens materials include encapsulation of drug within liposomes; incorporation of drug particles and nanoparticles directly into the lens material; use of polymer and fibrin films; and adding surfactants to control drug release. Additionally, lens-incorporated cyclodextrins contain hydrophobic cavities that can form inclusion complexes that foster slowed drug release.
Imprinting of drugs unto contact lenses has also been successfully accomplished.13 Further, drugs can be impregnated within lens material matrices through the use of solvents at high temperatures and pressures.14
Incorporating transport barriers into lenses is another promising approach for controlled elution of drugs. Barrier incorporation can be tuned to provide prolonged therapeutic levels of various drugs.15
• Microbial keratitis. Sight-threatening conditions, such as microbial keratitis, require rapid deployment of high levels of medication to the affected tissues. Currently, patients with severe microbial keratitis are hospitalized to ensure continuous delivery of therapeutic levels of antibiotic through round-the-clock dosing. Management of these patients could be dramatically improved through the use of an effective drug delivery system, ensuring continuously high antibiotic levels. Contact lens delivery of antibiotics has been investigated, yielding sustained, high therapeutic levels with potential utility for managing bacterial keratitis.16,17
• Glaucoma. Chronic ocular conditions, such as glaucoma, require long-term pharmacologic treatment. Frequent dosing often leads to compliance failures, making this an excellent application for the use of extended-release, drug-eluting contact lenses. A feasibility study investigating efficacy and toxicity of contact lenses that were passively impregnated with timolol maleate and brimonidine tartrate found IOP reductions equivalent to conventional therapy and no toxicity.18 This means that we can offer prolonged controlled drug delivery. A recent study found that contact lenses increased drug bioavailability and decreased systemic absorption.19
• Allergy. Patients with ocular allergy also could benefit from continuous delivery of therapeutic levels of allergy medication. The use of ketotifen-containing contact lenses for the management of ocular allergy has been investigated experimentally, and has also undergone several safety and efficacy clinical trials.20,21
• Dry eye. Another promising area for the use of drug-eluting contact lenses is the controlled release of phospholipids. Meibomian gland dysfunction (and dry eye in general) has been associated with a lack of phospholipids in the tear film. Phospholipids are an essential component contained in meibum, which acts to stabilize the tear layer. Phospholipid-eluting contact lenses may provide an effective treatment for some forms of dry eye, and possibly can improve end-of-day dryness in contact lens wearers by stabilizing the tear film and enhancing lens wettability.22 This may be especially helpful in wearers of silicone hydrogel lenses, which sequester lipids due to the hydrophobic nature of their surfaces.23
In addition to the familiar refractive and protective role soft contact lenses have played for the past 50 years, developments in drug delivery technology are likely to propel soft lenses to even greater heights of clinical significance in the future. Contact lenses are uniquely able to provide sustained effective levels of medication to the eye. Breakthroughs in drug delivery are also likely to help eliminate end-of-day dryness in contact lens wearers and offer help to dry eye sufferers. These advances in drug delivery technology are likely to extend the usefulness of contact lenses for the foreseeable future.
Dr. Epstein is a popular speaker and well-known author. He serves as an adjunct associate clinical professor at Midwestern University Eye Institute in Phoenix, Ariz. and is the Chief Medical Editor of Optometric Physician.
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