Abstract
There are several approaches to treat ocular diseases, which can be invasive or non-invasive. Within the non-invasive, new pharmaceutical strategies based on nanotechnology and mucoadhesive polymers are emerging methodologies, which aim to reach an efficient treatment of eye diseases. The aim of this work was the development of novel chitosan/hyaluronic acid nanoparticle systems with mucoadhesive properties, intended to encapsulate antioxidant molecules (e.g., crocin) aiming to reduce eye oxidative stress and, consequently, ocular disease. An ultraviolet (UV) absorber molecule, actinoquinol, was also added to the nanoparticles, to further decrease oxidative stress. The developed nanoparticles were characterized and the results showed a mean particle size lower than 400 nm, polydispersity index of 0.220 ± 0.034, positive zeta potential, and high yield. The nanoparticles were also characterized in terms of pH, osmolality, and viscosity. Mucoadhesion studies involving the determination of zeta potential, viscosity, and tackiness, showed a strong interaction between the nanoparticles and mucin. In vitro release studies using synthetic membranes in Franz diffusion cells were conducted to unravel the drug release kinetic profile. Ex vitro studies using pig eye scleras in Franz diffusion cells were performed to evaluate the permeation of the nanoparticles. Furthermore, in vitro assays using the ARPE-19 (adult retinal pigment epithelium) cell line showed that the nanoparticles can efficiently decrease oxidative stress and showed low cytotoxicity. Thus, the developed chitosan/hyaluronic acid nanoparticles are a promising system for the delivery of antioxidants to the eye, by increasing their residence time and controlling their delivery.
Highlights
Living beings are exposed to oxidative stress (OS) due to reactive oxygen species (ROS) produced within the cells or in the environment [1]
NPs of CS and hyaluronic acid (HA) were prepared aiming to interact with the ophthalmic mucosal barrier and to facilitate the transport of an antioxidant, crocin, and a UV absorber, ACT
The results show that the NPs were not stable 32 days after production, with significant differences in both size and Zeta Potential (ZP) values
Summary
Living beings are exposed to oxidative stress (OS) due to reactive oxygen species (ROS) produced within the cells or in the environment [1]. In the case of humans, some of the most exposed and vulnerable tissues are located in the eye, such as the anterior segment, cornea, lens, and trabecular meshwork [2,3]. The eyes are mostly affected by the incidence of UV radiation, which is responsible for some pathologies of the ocular tissues, such as glaucoma [2,3,4,5]. The eye has evolved excellent antioxidant defenses that act at different levels and are mainly located in the more exposed ocular tissues [3]. The eye is composed of several barriers with the function to keep the systematic circulation separated from the ocular tissues, such as the cornea, the barrier for topical drug absorption, the retina, the barrier to macromolecules, and the sclera, the barrier to diffusion of macromolecules [6,7,9]
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