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.

Solid Dispersion Incorporated into Dissolving Microneedles for Improved Antifungal Activity of Amphotericin B: In Vivo Study in a Fungal Keratitis Model

“…As shown in the figure, the administration of 0.1 M NaOH was used as a positive control because it could induce rapid and severe bleeding, which was considered a severe irritation, while the addition of NaCl 0.9% w/v was used as a negative control because it did not cause irritation, which indicated that it was considered safe. Meanwhile, for the treatment of all DMN-SD-AMB formulas after 5 min of observation, the appearance was similar to that of the negative control, which indicated that they did not show signs of damage to blood vessels . Thus, DMN-SD-AMB did not irritate the system and was deemed safe for application in in vivo studies.…”

“…Meanwhile, for the treatment of all DMN-SD-AMB formulas after 5 min of observation, the appearance was similar to that of the negative control, which indicated that they did not show signs of damage to blood vessels. 39 Thus, DMN-SD-AMB did not irritate the system and was deemed safe for application in in vivo studies.…”

“…After the inner membrane was removed, the chorioallantois membrane (CAM) was revealed and then treated using 0.3 mL aliquots of drug treatment, as well as a control group. Finally, the irritation reactions such as lysis, hemorrhage, and coagulation were observed visually at predetermined time endpoints (0.5, 2, and 5 min). , …”

“…Finally, the irritation reactions such as lysis, hemorrhage, and coagulation were observed visually at predetermined time endpoints (0.5, 2, and 5 min). 38,39 2.19. Ocular Tissue Preparation.…”

Biomimetic Lipid-polymer composite membrane model to study Permeability through Cornea

“…For the study, the cornea was separated from the eyeball and was cleaned thoroughly to remove any other adhered tissue using a standard solution. (Bhosale et al, 2022) The goat cornea was uniformly spread between the acceptor and donor compartment, as shown in Figure 1(B(iii)). After that, 14ml of PBS buffer at pH 7.4 was placed into the receptor compartment such that the cornea was in close contact with the buffer media.…”