<p>Clarithromycin-Loaded Ocular Chitosan Nanoparticle: Formulation, Optimization, Characterization, Ocular Irritation, and Antimicrobial Activity</p>

Abstract

Purpose: The topically administered drugs through conventional delivery systems have low bioavailability. Henceforth, the present study was designed to prepare and optimize clarithromycin (CTM)-loaded chitosan nanoparticles (CHNPs) to demonstrate the efficacy against microorganisms. Methods: Clarithromycin-loaded chitosan nanoparticles (CTM-CHNPs) were prepared by ionotropic gelation method. The formulation was optimized by box-Behnken design using the formulation variables like CH (A), STPP concentration (B), and stirring speed (C). Their effects were evaluated on the independent variables like particle size (Y 1 ) and entrapment efficiency (Y 2 ). Further, CTM-CHNPs were evaluated for physicochemical parameters, in-vitro drug release, ex-vivo permeation, bioadhesive study, corneal hydration, histopathology, HET-CAM, and antibacterial study. Results: The optimized formulation (CTM-CHNPopt) showed the low particle size (152± 5 nm), which is desirable for ocular delivery. It also showed high encapsulation (70.05%), zeta potential (+35.2 mV), and was found in a spherical shape. The drug release study revealed a sustained drug release profile (82.98± 3.5% in 12 hours) with Korsmeyer peppas kinetic (R 2 =0.996) release model. It showed a 2.7-fold higher corneal permeation than CTM-solution. CHNPs did not exhibit any sign of damage to excised goat cornea, which is confirmed by hydration, histopathology, and HET-CAM test. It exhibited significant ( P < 0.05) higher antibacterial susceptibility than CTM-solution. Conclusion: The finding of the study concluded that CTM-CHNPs can be used for effective management of bacterial conjunctivitis by increasing the precorneal residence time. Keywords: clarithromycin, chitosan, optimization, nanoparticles, HET-CAM, antimicrobial assessment

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