Introduction: The main purpose of the research was to develop, optimize and
characterize tobramycin sulphate loaded chitosan nanoparticles based gel in order to ameliorate
its therapeutic efficacy, precorneal residence time, stability, targeting and to provide
controlled release of the drug.
Methods: Box-Behnken design was used to optimize formulation by 3-factors (chitosan,
STPP and tween 80) and 3-levels. Developed formulation was subjected for characterizations
such as shape and surface morphology, zeta potential, particle size, in vitro drug release
studies, entrapment efficiency of drug, visual inspection, pH, viscosity, spreadability,
drug content, ex vivo transcorneal permeation studies, ocular tolerance test, antimicrobial
studies, isotonicity evaluation and histopathology studies.
Results: Based on the evaluation parameters, the optimized formulation showed a particle
size of 43.85 ± 0.86 nm and entrapment efficiency 91.56% ± 1.04, PDI 0.254. Cumulative
in vitro drug release was up to 92.21% ± 1.71 for 12 hours and drug content was found between
95.36% ± 1.25 to 98.8% ± 1.34. TEM analysis unfolded spherical shape of nanoparticles.
TS loaded nanoparticulate gel exhibited significantly higher transcorneal permeation
as well as bioadhesion when compared with marketed formulation. Ocular tolerance was
evaluated by HET-CAM test and formulation was non-irritant and well-tolerated. Histopathology
studies revealed that there was no evidence of damage to the normal structure of
the goat cornea. As per ICH guidelines, stability studies were conducted and were subjected
for 6 months.
Conclusion: Results revealed that the developed formulation could be an ideal substitute
for conventional eye drops for the treatment of bacterial keratitis.