Advancement on Sustained Antiviral Ocular Drug Delivery for Herpes Simplex Virus Keratitis: Recent Update on Potential Investigation

Abstract

The eyes are the window to the world and the key to communication, but they are vulnerable to multitudes of ailments. More serious than is thought, corneal infection by herpes simplex viruses (HSVs) is a prevalent yet silent cause of blindness in both the paediatric and adult population, especially if immunodeficient. Globally, there are 1.5 million new cases and forty thousand visual impairment cases reported yearly. The Herpetic Eye Disease Study recommends topical antiviral as the front-line therapy for HSV keratitis. Ironically, topical eye solutions undergo rapid nasolacrimal clearance, which necessitates oral drugs but there is a catch of systemic toxicity. The hurdle of antiviral penetration to reach an effective concentration is further complicated by drugs’ poor permeability and complex layers of ocular barriers. In this current review, novel delivery approaches for ocular herpetic infection, including nanocarriers, prodrugs, and peptides are widely investigated, with special focus on advantages, challenges, and recent updates on in situ gelling systems of ocular HSV infections. In general congruence, the novel drug delivery systems play a vital role in prolonging the ocular drug residence time to achieve controlled release of therapeutic agents at the application site, thus allowing superior ocular bioavailability yet fewer systemic side effects. Moreover, in situ gel functions synergistically with nanocarriers, prodrugs, and peptides. The findings support that novel drug delivery systems have potential in ophthalmic drug delivery of antiviral agents, and improve patient convenience when prolonged and chronic topical ocular deliveries are intended.

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“…The chemical stability was assessed by the estimation of % of the drug remaining in the formulation, pH, and physical stability, which was evaluated by monitoring any change in pH, viscosity, and appearance. [13,30,31]…”

Potential of Stimuli-Responsive In Situ Gel System for Sustained Ocular Drug Delivery: Recent Progress and Contemporary Research

“…Moreover, the mucoadhesive delivery system enables the drug release at targeted sites, hence bypassing first-pass degradation [16]. Thus, this system promotes local absorption due to the rich blood supply of mucosa, provides a localized effect, and subsequently improves ocular bioavailability along with therapeutic efficacy [5]. Morsi et al synthesized acetazolamide nanoemulsion-based in situ gel using xanthan gum, hydroxypropyl methylcellulose (HPMC), or Carbopol in the blend with gellan gum for glaucoma therapy.…”

“…The topical administration of ocular drugs remains the most widely accepted treatment route due to hassle-free and least invasiveness [2,3]. Nevertheless, the complex ophthalmic environment equipped with static, dynamic, and metabolic barriers makes topical drug delivery rather challenging [4,5]. Static barriers are the physical stumbling blocks of biological membranes that drugs must pass through to exert a pharmacological effect [2,6].…”

Blocking HSV-1 glycoprotein K binding to signal peptide peptidase reduces virus infectivity in vitro and in vivo

“…This study provides new insights into the determinants of HSV-1 replication and infectivity and provides a framework for the design of drugs that will offer new ways to combat herpesvirus infections with minimal to no side effects. In addition to the use of acyclovir and ganciclovir, nanocarriers, prodrugs, peptide conjugation, and in situ gelling systems have been used to slow the onset or progression of HSK and HSV-1 replication in vitro and in animal models [40,41,[54][55][56][57][58][59][60]. Therefore, these studies and many more have evaluated the antiviral activities of natural or synthesized compounds as potential treatments for viral keratitis.…”