Ocular formulations should provide an effective antibiotic concentration at the site of infection to treat bacterial eye infections. However, tears and frequent blinking accelerate the drug clearance rate and limit drug residence time on the ocular surface. This study describes a biological adhesion reticulate structure (BNP/CA-PEG) consisting of antibiotic-loaded bioadhesion nanoparticles (BNP/CA), with an average 500-600 nm diameter, and eight-arm NH2-PEG-NH2 for local and extended ocular drug delivery. This retention-prolonging effect is a function of the Schiff base reaction between groups on the surface of BNP and amidogen on PEG. BNP/CA-PEG showed significantly higher adhesion properties and better treatment efficacy in an ocular rat model with conjunctivitis in comparison to non-adhesive nanoparticles, BNP, or free antibiotics. Both in vivo safety experiment and in vitro cytotoxicity test verified the biocompatibility and biosafety of the biological adhesion reticulate structure, indicating a promising translational prospect for further clinical use.
Keywords: antibacterial nanoparticles; bacterial conjunctivitis; bioadhesive eye drops; biological adhesion reticulate structure; long-acting formulation; ocular drug delivery.