A variety of ocular diseases are caused by viruses, and most treatments rely on the use of systemic formulations and eye drops. The efficient ocular barriers that oppose antiviral drug penetration have prompted the development of improved topical delivery platforms. The aim was to design hydrogel contact lenses endowed with an affinity for acyclovir (ACV) and its prodrug valacyclovir (VACV), first-choice drugs against herpes simplex virus (HSV) ocular keratitis, and that can sustain the release of therapeutic doses during daily wearing. Functional monomers suitable for interaction with these drugs were screened using computational modeling. Imprinted and non-imprinted hydrogels were prepared with various contents in the functional monomer methacrylic acid (MAA) and characterized in terms of swelling, transmittance, mechanical properties, and ocular compatibility (hen’s egg test on chorioallantoic membrane (HET-CAM) assay). The values were in the range typical of soft contact lenses. Compared to ACV, the capability to load VACV was remarkably higher due to stronger electrostatic interactions with MAA. The advantages of the imprinting technology were evidenced for VACV. Stability of VACV loading solution/hydrogels under steam heat sterilization and subsequent drug release was investigated. Permeability studies through bovine and porcine cornea and sclera of the drug released from the hydrogels revealed that VACV accumulates in the cornea and can easily cross the sclera, which may facilitate the treatment of both anterior and posterior eye segments diseases.
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