Instant-gelling electrospun polyvinyl alcohol nanofiber mats for enhanced retinal drug delivery via topical ocular...

Topical application is the preferred route for drugs to treat ocular diseases, but most current eye drop preparations deliver active ingredients only transiently to surface structures. To enhance ocular drug delivery following topical application, we developed a preparation utilizing the unique property of polyvinyl alcohol (PVA) nanofibers to gel rapidly upon contact with minimal tear fluid on the ocular surface, thereby enhancing precorneal residence time. Coumarin 6 (C6), a poorly water-soluble fluorescent compound, was used as a tracer to evaluate the intraocular drug delivery by several PVA- and non-PVA-based preparations. C6 was incorporated into nanofibers via emulsion electrospinning and maintained in an amorphous state within the fibers to enhance solubility. Nanofibers were prepared using PVA with different polymerization and hydrolysis degrees. The corneal epithelial cell (CEC) damage potential was examined in monolayer culture by electrical resistance measures. All preparations demonstrated good biocompatibility without CEC barrier damage. The C6 release profiles varied depending on polymerization and hydrolysis degrees of PVA, indicating tunable release capacity. Low-polymerization PVA resulted in rapid C6 release, whereas completely hydrolyzed PVA enabled sustained release. C6 was barely detectable in mouse ocular tissue after topical administration of an aqueous suspension, while C6 dissolved in ethanol or encapsulated in liposomes reached peak ocular concentrations within 30 min, followed by a decline at 6 h. In contrast, administration of C6-containing nanofiber mats resulted in 5- to 18-fold higher retinal concentrations at 6 h compared to C6-containing liposomes. This PVA nanofiber-based system can safely prolong ocular drug delivery and improve bioavailability for poorly water-soluble compounds.