Raid G. Alany

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.

Traditional electrospinning is a promising technique for fabricating nanofibers for tissue engineering and drug delivery applications. The method is highly efficient in producing nanofibers with morphology and porosity similar to the extracellular matrix. Nonetheless, and in many instances, the process has faced several limitations, including weak mechanical strength, large diameter distributions, and scaling-up difficulties of its fabricated electrospun nanofibers. The constraints of the polymer solution’s intrinsic properties are primarily responsible for these limitations. Reactive electrospinning constitutes a novel and modified electrospinning techniques developed to overcome those challenges and improve the properties of the fabricated fibers intended for various biomedical applications. This review mainly addresses reactive electrospinning techniques, a relatively new approach for making in situ or post-crosslinked nanofibers. It provides an overview of and discusses the recent literature about chemical and photoreactive electrospinning, their various techniques, their biomedical applications, and FDA regulatory aspects related to their approval and marketing. Another aspect highlighted in this review is the use of crosslinking and reactive electrospinning techniques to enhance the fabricated nanofibers’ physicochemical and mechanical properties and make them more biocompatible and tailored for advanced intelligent drug delivery and tissue engineering applications.