Contact Lenses Incorporating Methotrexate-Loaded Chitosan/Hyaluronic Acid Nanoparticles.

Nanoparticle-laden contact lenses (CLs) represent a promising strategy for ocular drug delivery. Nanocarriers built from hyaluronic acid and chitosan offer a biomimetic alternative to synthetic polymers, by combining the lubricating property of hyaluronic acid with the mucoadhesive property of chitosan. However, achieving sustained drug release without compromising lens properties remains challenging, and the influence of lens material and replacement modality is unclear. This study evaluated methotrexate (MTX)-loaded chitosan/hyaluronic acid (CS/HA) nanoparticles incorporated into silicone hydrogel CLs with different replacement modalities, assessing their effect on drug release kinetics. Daily replacement lenses (Senofilcon A and Delefilcon A) released 26 ± 4% and 33 ± 5% of MTX after 24 h, respectively. The monthly lens Lehfilcon A showed slower diffusion-controlled release, with only 15 ± 2% released at 24 h and a 64 ± 3% cumulative release after 31 days (p < 0.01). Nanoparticle incorporation improved drug retention and reduced initial drug loss compared with lenses loaded with only MTX. Monthly lenses demonstrated sustained delivery potential, supporting prolonged ocular therapy, while daily lenses may be better suited for short-term treatment. These findings reinforce the value of bioinspired nanocarriers, mimicking natural retention mechanisms of the ocular surface, for next-generation therapeutic CLs.