DELIVERING DRUGS to the eye remains a challenge due to the eye’s ability to rapidly eliminate foreign substances. To address this, various strategies have been developed to prolong drug residence time on the ocular surface, including the use of contact lenses (Pelusi et al, 2023). A promising approach involves integrating aptamers into contact lenses.
Aptamers are short, single-stranded DNA or RNA molecules that fold into unique 3D structures, enabling them to bind to specific targets, such as proteins, small molecules, or cells, with high affinity and specificity. Often regarded as chemical analogs to antibodies, aptamers offer several advantages, including low immunogenicity, chemical stability, ease of modification, and cost-effective synthesis, making them ideal for ophthalmic drug delivery (Santarpia and Carnes, 2024).
Clinical Relevance in Eyecare
The US Food and Drug Administration (FDA) approvals of 2 anti-VEGF aptamers—namely pegaptanib (in 2004) and avacincaptad (in 2023) for treatment of age-related macular degeneration and geographic atrophy—marked key milestones (Bege et al, 2025). Importantly, when administered systemically, unmodified aptamers often suffer reduced specificity due to nonspecific interactions with plasma proteins in the bloodstream and are rapidly cleared through renal filtration due to their low molecular weight (Liu et al, 2023). Targeted delivery to the ocular surface using aptamer technologies, via eye drops or contact lenses, might overcome previous challenges of ocular surface drug delivery by enhancing residence time and retaining activity at the target site.
Aptamer Contact Lenses for Targeted Delivery
Aptamer-functionalized hydrogels have shown promise for controlled drug delivery, offering a minimally invasive, patient-friendly approach to managing chronic ocular diseases (Abune et al, 2021).
Aptamers have been developed against mucins on the ocular surface, corneal epithelial cells, and other ocular tissues (Wong et al, 2023; Korhonen et al, 2024; Wong, Liu, Wong, and Liu, 2024). Two of these aptamers have shown enhanced drug delivery efficiency when administered via eye drops (Wong et al, 2023; Wong, Liu, Phan et al, 2024). Incorporating such aptamers into contact lenses may improve targeting specificity and retention time for localized drug delivery onto the ocular surface.
Aptamer Contact Lenses for Biosensing
Beyond drug delivery, incorporating biosensor receptors, like aptamers, with contact lenses might enable continuous monitoring of ocular or systemic diseases through changes in optical or electrochemical signals (Shetty et al, 2024). A wearable aptamer-based sensor has been developed for noninvasive measurement of hormones in sweat (Wang et al, 2022).
The flexibility of aptamer sequences allows for rapid re-engineering to detect emerging biomarkers or multiple analytes simultaneously. This approach could be applied to detect markers of diabetic retinopathy or dry eye disease in tears (Cao et al, 2023).
Two aptamers have been selected for the ophthalmic drugs atropine and timolol maleate, with both demonstrating high specificity and favorable detection limits in artificial tears (Wong et al, 2024). Incorporating these biosensors into lenses could enable real-time, noninvasive monitoring of drug concentrations in tear fluid.
Challenges and Future Directions
Aptamer-functionalized contact lenses integrate molecular specificity with wearable technology, offering transformative potential for ocular drug delivery and diagnostics. Key challenges remain before clinical translation of aptamer-functionalized contact lenses, including aptamer stability in tear fluid, lens comfort and biocompatibility, and scalable, regulatory-compliant manufacturing.
References
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