Ganciclovir-Loaded Chitosan Nanoparticles and Their Activity against HSV-1 Inducing Herpetic Retinitis

Abstract

Herpes simplex virus (HSV)-1-induced retinitis is one of ophthalmic viral infections. It is found in some immunocompromised and elderly patients and is a cause of complete blindness. Nowadays, an intravitreal (IVT) injection of ganciclovir (GCV) is applied to treat this disease. Unfortunately, frequent IVT injections induce adverse effects in the eye. GCV-loaded chitosan nanoparticles (GCV-CS-NPs) were developed to reduce the number of IVT injections. This study developed GCV-CS-NPs and investigated their activity against HSV-1. GCV-CS-NPs were prepared using an ionic gelation method with varying formulation compositions. The particle size, polydispersity index (PDI), zeta potential, pH, drug release, and activity against the HSV-1 were investigated. The results showed GCV-CS-NPs with particle sizes of around 161 to 294 nm, moderate PDI values, and zeta potentials of between +8.0 and +18.1 mV. These properties strongly depended on the formulation compositions. The release rate of GCV from the optimized GCV-CS-NPs (3C-0.5G-1T-4.5) in the simulated vitreous humor regarding Higuchi’s model was 4.89±0.48 µg/min1/2. The IC50 against the HSV-1 was 25.12±0.02 µg/mL. 3C-0.5G-1T-4.5 could be accepted as a promising delivery system of GCV to the vitreous humor via IVT injection and had a potential for being subjected to further in vivo studies.