Chitosan/pectin nanoparticles encapsulating green coffee bean extract as a novel non-invasive therapy for dry eye...

Dry eye disease (DED) is a prevalent disease characterized by reduced tear production and ocular inflammation. The limitations of its current therapies have raised interest in exploring alternative natural therapies. Green coffee bean extract (GCBE) is one of these natural remedies which is rich in chlorogenic acid (CGA) with its well-known anti-inflammatory properties. However, GCBE possesses poor ocular bioavailability. This study aimed to develop GCBE-loaded chitosan/pectin nanoparticles (GCBE/CPNPs) using polyelectrolyte complexation. These nanoparticles were characterized and evaluated for in vitro drug release study using a dialysis bag method, ex vivo corneal permeation using modified Franz diffusion cell method, and in vivo corneal biodistribution using confocal laser scanning microscopy. DED was induced in rabbits by topical application of atropine sulfate (1 %). Tear production was assessed by Schirmer tear test. Anti-inflammatory potential was examined by investigating Bcl-2 level via immunohistochemistry. GCBE/CPNPs exhibited particle size of about 324.8 ± 21.87 nm and zeta potential of about +23.9 ± 0.21 mV, with high encapsulation efficiency of 94.8±6.49 %. In vitro release study demonstrated a biphasic release profile, reaching 91.55 ± 2.049 % after 24 h. Ex vivo corneal permeation study revealed a 13.49-fold increase in permeation of GCBE/CPNPs compared to free GCBE. In vivo biodistribution showed a 4.7-fold increase in accumulation of Rhodamine B-labeled CPNPs in comparison to free dye. In vivo studies in the DED rabbit model revealed that GCBE/CPNPs achieved a 12.1-fold increase in the percentage change of tear production and a 4.8-fold increase in the potential to alleviate inflammation when compared to free GCBE. These findings suggest that GCBE/CPNPs may represent a promising ocular delivery platform for managing DED.