Background: Intranasal administration of biodegradable nanoparticles has been extensively
studied for targeting the drug directly to CNS through the olfactory or trigeminal route bypassing the
blood brain barrier.
Objective: The objective of the present study was to optimize Clonazepam loaded PLGA nanoparticles
(CLO-PNPs) by investigating the effect of process variables on the responses using 32 full factorial
Methods: Effect of two independent factors-amount of PLGA and concentration of Poloxamer 188,
were studied at low, medium, and high levels on three dependent responses-%Entrapment efficiency,
Particle size (nm), and % cumulative drug release at 24hr.
Results: %EE, Particle size, and %CDR at 24hr of the optimized batch was 63.7%, 165.1 nm, and
86.96%, respectively. Nanoparticles were radiolabeled with 99mTc and biodistribution was investigated
in BALB/c mice after intranasal and intravenous administrations. Significantly higher brain/blood uptake
ratios and AUC values in the brain following intranasal administration of CLO-PNPs indicated
more effective brain targeting of CLO. Higher brain uptake of intranasal CLO-PNPs was confirmed by
rabbit brain scintigraphy imaging. A histopathological study performed on goat nasal mucosa revealed
no adverse response of nanoparticles. TEM image exhibited spherical shaped particles in the nano
range. DSC and XRD studies suggested Clonazepam encapsulation within the PLGA matrix. The onset
of occurrence of PTZ-induced seizures in rats was significantly delayed by intranasal nanoparticles as
compared to intranasal and intravenous CLO-SOL.
Conclusion: This investigation exhibits rapid rate and higher extent of CLO transport in the brain with
intranasal CLO-PNPs suggesting a better option as compared to oral and parenteral route in the management
of acute status epilepticus.