Imprinted Contact Lenses for Ocular Administration of Antiviral Drugs

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.

Contact Lenses as Ophthalmic Drug Delivery Systems: A Review

“…Molecular imprinting is another novel method recently employed to prepare therapeutic contact lenses [ 22 , 60 ]. It consists of the addition of a template molecule (specifically, the ophthalmic drug) to a monomer solution, with the aim of inducing a spatial arrangement of the monomers according to their ability to interact with the drug-template [ 96 , 97 , 98 ].…”

“…When imprinted systems are employed for drug delivery, a sustained-release of the drug-template is generally promoted because of the polymer–drug interactions. For example, the advantage of using imprinting technology is evident from the results of the study of Varela-Garcia et al [ 60 ], which focused on the development of hydrogel contact lenses with a strong affinity for acyclovir and its prodrug valacyclovir, generally prescribed to the treatment of herpes simplex virus in the eye. In particular, the valacyclovir loading was significantly higher than the amount of loaded acyclovir, due the stronger interactions of valacyclovir with the methacrylic acid contained in the hydrogel network.…”

In Vivo Efficacy of Contact Lens Drug-Delivery Systems in Glaucoma Management. A Systematic Review

“…This technique increased the CL drug loading capacity [56]. It has been applied to different ophthalmic drugs-hyaluronic acid, prednisolone, diclofenac, ketotifen fumarate, norfloxacin, and acyclovir [57][58][59][60][61][62]. However, to date, only timolol has been investigated in vivo among hypotensive drugs.…”

Therapeutic Ophthalmic Lenses: A Review

“…Promising new strategies have been suggested for a wider approach to the anterior segment pathologies, addressing, for example, neurotrophic keratitis, persistent epithelial defects, diabetic keratopathy, and diabetic neuropathy, such as the use of topical insulin, naltrexone, ARIs, substance P, and different growth factors [160,169,170,174,200]. Poly-ε-lysine [190] Antifungals CL Silicone hydrogel (N/A) [191,194] Poly-ε-lysine [193] HEMA-PC [194] HEMA-MAA [194] HEMA-MAA-PVP [189,194] Sil-DMA-HEMA-PVP [194] Quaternized chitosan + graphene oxide [192] Antivirals CL HEMA-MAA [195,196] Collagen photosensitizer Riboflavin CL HEMA-PVP [197,199,201] Sil-DMA [201] PVP-MMA [201] Opioid antagonist Naltrexone CL HEMA [87] [44,45] Naltrexone (NTX) is an opioid antagonist, whose systemic or topical administration proved to block the negative effect of opioid growth factors, which are excessively present in diabetic patients, on cell proliferation and tissue growth. The use of naltrexone eye drops resulted in an accelerated corneal wound healing and the restoration of corneal sensitivity in many animal models, and it is considered to be a promising treatment of diabetic keratopathy [160,174].…”

“…In recent years, several examples of the mentioned drugs have been incorporated into CLs using many different techniques, and the obtained results have been extensively discussed in previous review papers [ 21 , 111 , 186 ]. Therapeutic CLs for the treatment of keratitis have also been widely reported in literature reviews [ 187 , 188 ], with promising results for the delivery of biocides [ 189 , 190 ], antifungals [ 189 , 191 , 192 , 193 , 194 ], and antiviral drugs [ 195 , 196 ].…”