Natural gum-modified mucin nanocarriers with enhanced mucoadhesion and trans-cornea infiltration for controlled drug delivery in ocular uveitis therapy

Abstract

Ocular uveitis is a major health concern due to the limited efficacy of current antibiotic eye drops. Conventional treatments require frequent reapplication as they have low bioavailability and show slow drug action at the infection site. To address this, a novel eye drop formulation was developed using mucin-based nanoparticles (Mu NPs) that encapsulate ciprofloxacin. In the ionic gelation technique, the COO⁻ groups of the mucin chain interacted electrostatically with cationic crosslinkers to form NPs, and then, Mu NPs were stabilized using xanthan gum for extended shelf life. TEM and DLS studies confirmed variations in particle size and surface charge based on the crosslinker concentration. In vitro, ex vivo, and in vivo biocompatibility tests showed excellent safety, including <4% hemolysis ratio, and the Draize test also confirmed the biocompatibility. The formulation had 95% drug encapsulation efficiency and controlled drug release rate with 40–50% release in the first 8 hours. In rabbit eye models, induced inflammation and bacterial infection were treated successfully within 3 and 7 days, respectively. The histopathological analysis of infected corneas proved the completion of internal healing. The high mucoadhesiveness of mucin enhanced drug retention in the aqueous humor (0.26 µg mL⁻¹) even after 8 hours, outperforming commercial eyedrops. These findings suggest mucin NPs as a promising mucoadhesive drug delivery system for infectious and inflammatory eye diseases.