Preparation and Evaluation of Modified Chitosan Nanoparticles Using Anionic Sodium Alginate Polymer for Treatment of Ocular Disease

Abstract

Mucoadhesive nanoparticles offer prolonged drug residence time at the corneal epithelium by adhering to the mucous layer of the eye. Here, in this research investigation, voriconazole-loaded chitosan mucoadhesive nanoparticles (VCZ-MA-NPs) were modified to mucous-penetrating nanoparticles (VCZ-MP-NPs) by coating them with anionic polymer sodium alginate. The ionic gelation method was utilized to prepare mucoadhesive chitosan nanoparticles, which were further coated with sodium alginate to obtain the surface properties essential for mucous penetration. The developed VCZ-MA-NPs and VCZ-MP-NPs were evaluated extensively for physicochemical delineation, as well as in vitro and ex vivo studies. The particle size, polydispersity index, and ζ potential of the VCZ-MA-NPs were discovered to be 116 ± 2 nm, 0.23 ± 0.004, and +16.3 ± 0.9 mV, while the equivalent values for VCZ-MP-NPs were 185 ± 1 nm, 0.20 ± 0.01, and −24 ± 0.9 mV, respectively. The entrapment efficiency and drug loading were obtained as 88.06%±1.29% and 7.27% ± 0.95% for VCZ-MA-NPs and 91.31% ± 1.05% and 10.38% ± 0.87% for VCZ-MP-NPs, respectively. The formulations were found to be stable under different conditions (4 °C, 25 °C, and 40 °C). Chitosan nanoparticles and modified nanoparticles showed a spherical and smooth morphology under electron microscopic imaging. An excised caprine cornea was used for the ex vivo permeation study, exhibiting 58.98% ± 0.54% and 70.02% ± 0.61% drug permeation for VCZ-MA-NPs and VCZ-MP-NPs, respectively. The findings revealed that the mucous-penetrating nanoparticles could effectively pass through the corneal epithelium, thus overcoming the mucous barrier and fungal layer of the eye, which highlights their potential in the treatment of fungal keratitis.

Keywords

• fungal keratitis
• chitosan
• voriconazole
• mucoadhesive
• mucous penetrating
• ophthalmic