Development of gum-based chitosan nanoparticle with improved functional properties for conjunctivitis treatment

Abstract

Conjunctivitis, commonly known as pink eye, is a widespread eye condition characterized by inflammation or infection of the conjunctiva, the thin membrane covering the white part of the eye and the inner eyelids. Treating conjunctivitis effectively can be challenging due to the limitations of traditional drug delivery methods, such as eye drops, which often do not provide sufficient drug retention and can lead to systemic side effects. This study presents an innovative dual-drug delivery approach that involves encapsulating two powerful medications—dexamethasone (DEX), a corticosteroid that reduces inflammation, and moxifloxacin (MOX), an antibiotic effective against bacterial infections—within chitosan nanoparticles (CSNPs). These nanoparticles are further enhanced with various natural gums used as crosslinker, including Arabic gum, tamarind gum, guar gum, gellan gum, and xanthan gum. The inclusion of these gums aims to improve the mucoadhesive properties of the formulations, which helps them adhere better to the ocular surface and increases the availability of the drugs where they are needed most. The study conducted comprehensive evaluations through various tests—in vitro, ex vivo, and in vivo to assess the effectiveness, biocompatibility, and ability of these formulations to retain drugs on the eye's surface. Among the formulations tested, Arabic gum-based chitosan nanoparticles (CS-A-0.03) showed optimal characteristics, including a particle size of ~200 nm and high stability. These nanoparticles demonstrated excellent drug encapsulation efficiency (97 ± 1.96%. for DEX, 58.72 ± 5% for MOX) and controlled release over 5 hours. The formulation exhibited biocompatibility with only 0.28±0.09% hemolysis and no corneal tissue damage. Notably, the CS-A nanoparticles showed 73.91±0.25% mucoadhesion, significantly higher than commercial eye drops (64±3.5%). In vivo tests revealed faster and more effective inflammation reduction compared to conventional treatments. The long-term stability study showed that CS-A based formulations remained stable for 12 months at room temperature. The results demonstrated significant improvements in therapeutic outcomes when compared to conventional eye drop treatments. Specifically, these new formulations showed enhanced drug retention time on the ocular surface, addressing critical issues associated with traditional treatments.