Micro-interaction of montmorillonite-loaded nanoparticles with mucin promotes retention of betaxolol hydrochloride on the ocular surface and the tear film microenvironment

Abstract

This work developed a triple-encapsulated nano-delivery system for topical and long-term glaucoma treatment. We encapsulated betaxolol hydrochloride (BH), a glaucoma drug loaded in refined acid-treated montmorillonite (RAMt), in hyaluronic acid/chitosan (HA/CS) cross-linked nanoparticles with high encapsulation efficiency and further wrapped them with Eudragit (ED) films to achieve dual sustained release. RAMt-BH-HA/CS@ED NPs exhibited excellent physicochemical properties for the sustained release of betaxolol hydrochloride. In vitro release experiments were performed, and the results showed that the drug release lasted for up to 8 h. Then, particle surface hydrophobicity experiments showed that the nanoparticles had both hydrophilic and hydrophobic properties. The ocular safety of the nanoparticles was confirmed by the chick embryo allantoic membrane assay and the rabbit blink frequency test. In the mucin-nanoparticle interaction experiments, the interaction between the nanoparticles and the mucin solution with high pH and low concentration (simulating the aqueous layer microenvironment of tears) was stronger than that with low pH and high concentration (simulating the tear mucin layer microenvironment of tears). Therefore, the nanoparticles showed excellent retention properties in tears and cornea. In vivo experiments in a rabbit model of elevated intraocular pressure demonstrated that the IOP-lowering effect was sustained for more than 12 hours. In conclusion, nanoparticles effectively lower IOP with excellent tolerability, and offer promising applications for long-term treatment of glaucoma.