ABSTRACT
Rho-kinase (ROCK) inhibitors represent a new category of anti-glaucoma medications. Among them, Fasudil hydrochloride, a selective ROCK inhibitor, has demonstrated promising outcomes in glaucoma treatment. It works by inhibiting the ROCK pathway, which plays a crucial role in regulating the trabecular meshwork and canal of Schlemm's aqueous humor outflow. This study aims to investigate the ocular absorption pathway of Fasudil hydrochloride and, subsequently, develop a nanoparticle-based delivery system for enhanced corneal absorption. Employing the ionic gelation method and statistical experimental design, the factors influencing chitosan nanoparticle (Cs NP) characteristics and performance were explored. Fasudil in vitro release and ex vivo permeation studies were performed, and Cs NP ocular tolerability and cytotoxicity on human lens epithelial cells were evaluated. Permeation studies on excised bovine eyes revealed significantly higher Fasudil permeation through the sclera compared to the cornea (370.0 µg/cm2 vs. 96.8 µg/cm2, respectively). The nanoparticle size (144.0 ± 15.6 nm to 835.9 ± 23.4 nm) and entrapment efficiency range achieved (17.2% to 41.4%) were predominantly influenced by chitosan quantity. Cs NPs showed a substantial improvement in the permeation of Fasudil via the cornea, along with slower release compared to the Fasudil aqueous solution. The results from the Hen's Egg Test Chorioallantoic Membrane (HET-CAM) and Bovine Corneal Opacity and Permeability (BCOP) tests indicated good conjunctival and corneal biocompatibility of the formulated chitosan nanoparticles, respectively. Lens epithelial cells displayed excellent tolerance to low concentrations of these nanoparticles (>94% cell viability). To the best of our knowledge, this is the first report on the ocular absorption pathway of topically applied Fasudil hydrochloride where the cornea has been identified as a potential barrier that could be overcome using Cs NPs.
ABSTRACT
In the last few decades, the interest in biodegradable materials for biomedical applications has increased significantly. Both natural and synthetic biodegradable polymers (BDPs) have been broadly explored for various biomedical applications. These include sutures and wound dressings, screws for bone fracture, scaffolds in tissue engineering, implants, and other carriers for targeted and sustained release drug delivery. Owing to their unique characteristics, including their surface charge variable copolymer block and composition and film-forming properties, BDPs have been widely used as favourable materials for ophthalmic drug delivery. Mucoadhesive BDPs have been used in ophthalmic formulations to prolong drug retention time and improve bioavailability, allowing ophthalmic controlled release systems to design. Furthermore, BDPs-based implants, microneedles, and injectable nano- and micro-particles enabled ocular posterior segment targeting and, most importantly, circumvented the need for removing the delivery systems after application. This review outlines the major advances of BDPs and highlights the latest progress of employing natural and synthetic BDPs for various biomedical applications, emphasising the treatment and management of ophthalmic conditions.
