Abstract
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.
Highlights
Infection by herpes simplex virus (HSV) starts when the virus comes into contact with damaged skin or mucous membranes; the incubation period extends to 4 days [1]
Farmalabor (Canosa di Puglia, Italy); valacyclovir hydrochloride (VACV; MW 360.80 g/mol; solubility in water 174 mg/mL [36]) was from Acros Organics (Geel, Belgium); 2,20 -azo-bis(isobutyronitrile) (AIBN), dichlorodimethylsilane, ethylene glycol dimethacrylate (EGDMA), and methacrylic acid (MAA) were from Sigma-Aldrich (Steinheim, Germany); ethanol absolute and NaOH were from VWR (Leuven, Belgium); 2-hydroxyethyl methacrylate (HEMA) was from Merck (Darmstadt, Germany); acetic acid and NaCl were from Scharlau (Sentmenat, Spain); and methanol was from Fisher (Loughborough, UK)
Acyclovir and valacyclovir behaved differently when incorporated into HEMA-based hydrogels, despite their similar chemical structure and a priori similar binding energy with MAA
Summary
Infection by herpes simplex virus (HSV) starts when the virus comes into contact with damaged skin or mucous membranes; the incubation period extends to 4 days [1]. There are two subtypes of herpes simplex virus, HSV-1 and HSV-2. 90% of the world’s population is infected with HSV [2]. The virus can reactivate and travel to the skin or mucous membranes, causing a recurrent symptomatic or asymptomatic infection. Many factors can trigger this reactivation, for example, stress, exposure to heat or cold, menstruation, fever, or immunosuppression [3]. The clinical manifestations depend on whether the infection is primary or recurrent, the immune status of the host, and the entry portal [4]
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