Patients typically use topical eye drops to deliver ophthalmic medications; however, limitations such as low bioavailability and patient compliance have led researchers to explore alternative methods for drug delivery.

With technological advancements, ocular drugs can now be administered through means other than drops, including modified inserts and contact lens (CL) materials. This article focuses on the application of these alternative drug delivery methods to specific ocular diseases.

Insert Uses

Dry eye disease (DED) therapies often include the use of artificial tear solutions (ATs). However, ATs are often insufficient, as frequent instillation is needed for adequate relief. A daily replaceable insert has found success in reducing signs and symptoms of DED, as its dissolvable design releases hydroxypropyl cellulose into the tear film over time. (Luchs et al, 2010; Koffler et al, 2010; McDonald et al, 2009; McDonald et al, 2010).

Researchers have also demonstrated sustained release of hyaluronic acid and hydroxypropyl methylcellulose from model CLs using a polymerization technique known as molecular imprinting, which involves the modification of polymers to tailor release of these tear enhancers (Ali and Byrne, 2009; White et al, 2011).

DED drug release, such as cyclosporine from CLs, has also been found to be material dependent (Jones et al, 2021; Peng & Chauhan, 2011). While cyclosporine release can be maintained for one day with hydrophilic, ionic etafilcon A lenses, it can be extended to upwards of two weeks with silicone hydrogels due to hydrophobic interactions with the material (Peng and Chauhan, 2011).

Patient compliance with glaucoma medication regimens tends to be poor. Hence, sustained drug release through fornix-based inserts and CLs have been explored. A pilocarpine-releasing insert was previously made commercially available; however, its success was limited due to discomfort and side effects (Brandt et al, 2016).

Timolol-loaded CLs with various modifications have been studied, leading to different release kinetics that allow sustained release times. For instance, vitamin E coating on CLs can serve as a diffusion barrier for the passage of drug, leading to significantly extended release compared to unmodified CLs (Peng et al, 2012).

Contact Lens Uses

For patients who suffer from allergic conjunctivitis, CL wear should be monitored due to the discomfort and risk of damage from rubbing in response to an ocular itch (Lemp, 2008; Najmi et al, 2019; Ackerman et al, 2016). But CL wear in allergy season does have its benefits, as it may act as a barrier to the eye and provide protection against allergens present in the environment (Wolffsohn and Emberlin, 2011). A commercially available lens that releases ketotifen fumarate has been released in Canada and Japan (Pall et al, 2019). Molecularly imprinted olopatadine-loaded CLs have also been developed and can inhibit the release of histamine from mast cells in vitro (González-Chomón et al, 2016).

Alternate Delivery Systems

The discussed drug delivery systems are diffusion-kinetics dependent, meaning drug release is mitigated by differences in concentration (Choi and Kim, 2018; Maulvi et al, 2016). However, to efficiently treat ocular diseases, incorporation of “on-demand” systems or “smart” intelligent materials triggering drug release in response to stimuli would provide timelier therapy.

Enzyme-triggered release has been discussed as a potential system for drug delivery, in which enzymes within the tear film could be harnessed to trigger drug release. In one example, CLs loaded with chitosan-poly nanoparticles have shown to release the nanoparticles in the presence of lysozyme over a 28-hour period (Åhlén et al, 2018). With increased presence of certain enzymes on the ocular surface in different disease states, an enzyme-triggered release system could potentially be tailored to treat specific diseases, thus allowing for more efficient treatment.

With further advancements in technology, the future remains promising for this field. CLS

References

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