Clarithromycin-Loaded Ocular Chitosan Nanoparticle: Formulation, Optimization, Characterization, Ocular Irritation,...

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.

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 (Y₁) and entrapment efficiency (Y₂). 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.

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 (R²=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.

The finding of the study concluded that CTM-CHNPs can be used for effective management of bacterial conjunctivitis by increasing the precorneal residence time.