Development and Characterization of PLGA Nanoparticle-Laden Hydrogels for Sustained Ocular Delivery of Norfloxacin in the Treatment of Pseudomonas Keratitis: An Experimental Study
Rana M. Gebreel, Noha Ahmed Edris, Hala Mohammed El-Mofty, Mina Ibrahim Tadros, Mohamed A. El-Nabarawi, Doaa H. Hassan
Abstract
Aim: 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. Methods: NFX-loaded NPs were developed via the double-emulsion/solvent evaporation technique, according to 2 1 .4 1 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 (Q 30min ) and 12 hours (Q 12h ), drug percentage permeated through goat corneas after 30 min (P 30min ) and 12 hours (P 12h ) 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. Results: 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 Q 30min (10.96% and 16.65%) and P 30min (17.39% and 21.05%) and promising Q 12h (58.23% and 71.20%) and P 12h (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. Conclusion: G3 and G4 are potential ocular delivery systems for NFX. Keywords: norfloxacin, nanoparticles, PLGA, ocular delivery, Pseudomonas keratitis