Formulation, Optimization and Evaluation of Antibacterial Nanoparticle-Loaded in Situ Gel for Enhanced Ocular Drug Delivery

Bacterial conjunctivitis is a common ocular infection requiring effective antimicrobial therapy. Conventional ophthalmic preparations of ciprofloxacin hydrochloride have limited ocular residence time due to tear drainage and blinking, which may reduce therapeutic effectiveness. The present study aimed to formulate, optimize and evaluate ciprofloxacin hydrochloride-loaded chitosan nanoparticles incorporated into a thermoreversible in situ gel for enhanced ocular drug delivery. Ciprofloxacin hydrochloride was characterized by preformulation studies, showing a λmax of 277 nm, saturation solubility of 13.6 ± 0.05 mg/mL in distilled water and 11.4 ± 0.05 mg/mL in simulated tear fluid, an average melting point of 316°C and a DSC endothermic peak at 319°C. FTIR studies confirmed drug identity and compatibility with the selected excipients. Nanoparticles were prepared by ionic gelation using chitosan and sodium tripolyphosphate and optimized using a central composite design. The optimized nanoparticles containing 0.2% chitosan and 0.1% tripolyphosphate exhibited a particle size of 266.8 nm, PDI of 0.25, zeta potential of +20.6 mV, entrapment efficiency of 71.05% and drug content of 35.5%. SEM confirmed spherical nanoparticles. The optimized nanoparticles were incorporated into 19% w/v Poloxamer 407 in situ gel. The formulation showed a gelation temperature of 35.36 ± 0.31°C, gelation time of 66 seconds, pH of 7.2 ± 0.2, solution viscosity of 130 ± 4.1 and gel viscosity of 6454 ± 4.5, with 83% drug content. In vitro release reached 78.5% at 8 hours and followed the Korsmeyer–Peppas model (R² = 0.9954; n = 1.4886), indicating Super Case-II transport. Ex vivo corneal permeation reached 41.07% at 4 hours. The formulation showed antibacterial activity against S. aureus and E. coli, with zones of inhibition of 3.1 ± 0.2 and 3.4 ± 1.2 cm, respectively. Thus, the developed formulation demonstrated sustained drug release, corneal permeation and promising antibacterial activity, indicating its potential for ocular delivery of ciprofloxacin hydrochloride.