Brinzolamide encapsulated β-cyclodextrin-chondroitin sulfate nanocomplexes anchored chitosan/polycaprolactone nanofibers as an ocular insert for glaucoma treatment

Glaucoma ranked second among the causes of blindness globally, necessitates the development of novel and effective therapeutic strategy. Anti-glaucoma eye drops as a topical dosage form are still considered as a method of choice for glaucoma treatment. However, a short ocular drug residence time of eye drops leads to poor bioavailability of drug which requires repeated dosing. Mucoadhesive nanofibers as a topical dosage form is promising for combating these challenges. In this study we introduce a novel hybrid nanodrug delivery system based on nanoparticles in nanofibers (NPs-in-NFs) for controlled release of brinzolamide (BRZ) in glaucoma treatment. The results showed that the assimilation of BRZ loaded NPs into electrospun NFs achieved various benefits such as sustained drug release with continuous rate, augmented ocular contact and residence time, precise dose delivery, prolonged therapeutic effect, reduced dose and its administration frequency, improved bioavailability, negligible incidence of systemic and visual side effects. Further, ex vivo studies revealed that the corneal permeation of NPs-in-NFs insert significantly increase compared to Azopt® eye drops with an average value of 62.34 ± 2.4 μg/cm² and 39.06 ± 1.9 μg/cm², respectively. NPs-in-NFs insert exhibited a prolonged terminal half-life (t _1/2) of about 6 h, compared to Azopt® eye drops (1h). Moreover, at 96h of dose administration, a significant decrease (14.48 ± 2.65 mm Hg) was observed in the IOP of NPs-in-NFs administered rabbits (21.06 ± 2.51 mm Hg) compared with Azopt® eye drops administered rabbits (35.54 ± 3.60 mm Hg). Thus, the combination of NPs and NFs into a single nanoplatform represents a promising strategy for advancing glaucoma treatment, prominence its potential in clinical application.

Glaucoma; Mucoadhesion; Nanofibers; Nanoparticles; brinzolamide.