Green development of Cefuroxime-Loaded Chitosan Nanoparticle Microneedles using citric acid crosslinker: A New Approach for targeted Ocular Infection

This study aims to develop chitosan nanoparticles containing cefuroxime sodium, a BCS class 3 drug, which was encapsulated into the nanoparticles using a gelation method and then loaded into dissolving microneedles (DMNs) to enable ocular drug delivery. The nanoparticle formula contained chitosan, citric acid, cefuroxime sodium, and Pluronic F127 at a ratio of (1:1:1:0.05) and exhibited a particle size of 509.97 ± 0.47 nm, and entrapment efficiency (EE%) of 44.94%. The DMNs, prepared by the casting method, was fabricated from carboxymethyl cellulose sodium, sucrose, and polyvinylpyrrolidone, exhibited excellent mechanical strength. The nanoparticle-loaded DMNs successfully penetrated the corneal layer, with a cumulative drug delivery of 75.32 µg/cm2, which was significantly higher than that of DMNs loaded with conventional cefuroxime sodium. The nanoparticle formulation and the conventional cefuroxime sodium formulation had the same minimum inhibitory concentration of 0.90 µg/mL against Staphylococcus aureus, indicating that the pharmacological action was conserved. Additionally, compared to the conventional cefuroxime sodium (2.88 ± 0.05 cm), the nanoparticle formulation showed a noticeably broader inhibitory zone (3.48 ± 0.05 cm), suggesting an increase in antibacterial diffusion. In conclusion, the fabricated DMNs demonstrated sufficient mechanical strength to effectively penetrate the cornea and dissolve rapidly, which highlights their potential as a promising strategy for ocular drug delivery