Development and Characterization of PLGA Nanoparticle-Laden Hydrogels for Sustained Ocular Delivery of Norfloxacin in the Treatment of Pseudomonas Keratitis: An Experimental Study

Norfloxacin (NFX) has low ocular bioavailability. The current work aimed to develop NFX-loaded nanoparticle (NP)-laden hydrogels to improve the ocular potential of NFX, minimize the need for frequent instillations and lower undesirable side effects.NFX-loaded NPs were developed via the double-emulsion/solvent evaporation technique, according to 21.41 full factorial design, using two types of polylactic-co-glycolic acid (PLGA) polymer and four (drug: polymer) ratios. NPs were evaluated for particle size (PS), polydispersity index (PDI), zeta potential (ZP), drug entrapment efficiency percentage (EE%), drug percentage released after 30 min (Q30min) and 12 hours (Q12h), drug percentage permeated through goat corneas after 30 min (P30min) and 12 hours (P12h) and morphology. Two formulae were statistically selected and incorporated into hydroxypropyl methylcellulose (HPMC)-based hydrogels; G1 - G4. The latter systems were evaluated for appearance, clarity, pH, spreadability, rheology, drug percentages released, drug percentages permeated, antimicrobial activity against Pseudomonas aeruginosa, and histopathological changes.The selected NPs (NP2 and NP6) were spherical in shape and possessed suitable PS (392.02 nm and 190.51 nm) and PDI (0.17 and 0.18), high magnitude of ZP (-30.43 mV and -33.62 mV), high EE% (79.24% and 91.72%), low Q30min (10.96% and 16.65%) and P30min (17.39% and 21.05%) and promising Q12h (58.23% and 71.20%) and P12h (53.31% and 65.01%), respectively. Clear, spreadable, tolerable, pseudoplastic, and thixotropic HPMC-based hydrogels were developed. They showed more prolonged drug release and drug permeation profiles. NP2- and NP6-laden hydrogels (G3 and G4 systems, respectively) had promising antibacterial activity, and reasonable histopathological safety.G3 and G4 are potential ocular delivery systems for NFX.