Validation of biocompatible nanofiber membranes based on polyvinyl alcohol and carboxymethylcellulose blend as an ophthalmic drug deliverer and tear viscosity improver

Abstract

Purpose : To validate a biocompatible nanofiber membrane based on polyvinyl alcohol (PVA) and carboxymethylcellulose (CMC) blend as an ophthalmic drug deliverer and tear viscosity improver to treat dry eye disease (DED)

Methods : Water-based PVA and CMC polymer solutions were mixed in different ratios to prepare the nanofiber membrane by electrospinning. Small pieces of the membrane were cut to study the morphology, chemistry, thermal, and mechanical properties with scanning electron microscopy (SEM), infrared spectroscopy, differential scanning calorimetry, and dynamical mechanical analysis, respectively. Hydrophobic properties were analyzed with contact angle on artificial tears. HELA cell viability was evaluated in the presence of an increasing number of membrane sheets. Membrane persistence on the conjunctival fornix, ocular surface staining (OSS) with fluoresceine graded with NEI-CLEK score, tear film stability with fluorescein tear film break-up time (FBUT) test, and conjunctival histology analysis were performed on a rabbit model. All procedures were approved by the faculty ethics committee.

Results : Lower polymer concentrations and lower CMC:PVA ratios yield the best results; thinner nanofibers with a diameter of 196nm ±55nm and free of defects. The operational parameters were optimized to obtain a nanostructured morphology. Regarding the hydrophobic properties, a contact angle of between 30° and 46° was observed, implying hydrophilic behavior that was validated in solubility assays. The cell viability assays showed a reduction of up to 51% at 72h regardless of the number of membranes suggesting that it was due to a viscosity-saturation in the in-vitro culture. An improvement in ΔFBUT after 2h (+2.2) and 24 h (+0.8) was observed. No changes were observed in OSS. The persistence of the membrane in the rabbit fornix was 100%, 50% and 10% at 2h, 1 day, and 3rd day. The membrane loss was related to the nictitating membrane of the rabbit eyelid and animal scratching. Macroscopic and histological analysis showed the absence of ocular surface lesions.

Conclusions : This PVA/CMC nanofiber membrane is hydrophilic and improves tear viscosity for at least 24 h without injuring the ocular surface at 2 and 24h. This makes it a viable proposal for dry eye therapy to reduce the need for multiple eye drop administrations throughout the day.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.