Norfloxacin Loaded pH Triggered Nanoparticulate in-situ Gel for Extraocular Bacterial Infections: Optimization, Ocular Irritancy and Corneal Toxicity

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In order to achieve prolong corneal contact time of norfloxacin (NFX) for treatment of extra ocular diseases, a pH triggered nanoparticulate in-situ gelling system was designed to explore dual advantage of nanoparticles and in-situ gelling system, for its ocular delivery. NFX loaded nanocarriers were developed by ionotropic gelation technique using chitosan as a matrix forming polymer, cross-linked by an anionic crosslinker sodium tripolyphosphate (TPP). Optimization of nanoformulations was done by 32 full factorial design using chitosan and TPP concentration(s) as the independent variables and particle size, % entrapment efficiency and % cumulative drug release as the responses. The experimental design was validated by extra design check point formulation (N10). The optimized formulation (N4) selected on the basis of highest desirability factor (0.895) was developed as in-situ gelling system using carbapol934 and evaluated. The best in-situ gelling formulation (N4G5) was sufficiently mucoadhesive, corneal toxicity, antibacterial activity and free from ocular irritancy.