Background: Intranasal administration of biodegradable nanoparticles has been extensively studied for targeting the drug
directly to CNS through olfactory or trigeminal route bypassing 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 design.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 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 & intravenous administrations.
Significantly higher brain/blood uptake ratios and AUC values in 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. Histopathological study performed on goat nasal mucosa revealed no adverse response of nanoparticles. TEM image exhibited
spherical shaped particles in nano range. DSC and XRD studies suggested Clonazepam encapsulation within PLGA matrix. The onset
of occurrence of PTZ-induced seizures in rats was significantly delayed by intranasal nanoparticles as compared to intranasal & intravenous CLO-SOL.Conclusion: This investigation exhibits rapid rate and higher extent of CLO transport in brain with intranasal CLO-PNPs suggesting
a better option as compared to oral & parenteral route in management of acute status epilepticus.
We present a comprehensive investigation
on the interaction of
tetronics (T1304 and T1307) with some important physiological salts
(NaH2PO4, KH2PO4, Na2CO3, NaCl, and KI). Thermodynamic and microstructural
aspects of these interactions were studied as a function of the solution
temperature, pH and salt concentration. Characterizations were performed
using turbidimetric, calorimetric, and scattering techniques. We show
that, at ambient temperature, T1304 molecules aggregated to form spherical
core–shell aggregates displaying a unimodal distribution pattern.
On the other hand, unimers and large clusters dominated in the case
of highly hydrophilic T1307. Its micellization was promoted in the
presence of salts as per the following trend: NaCl < KH2PO4 < NaH2PO4 ≪ Na2CO3. Aggregation was found to be endothermic, and
hydrophobic interactions (TΔS
mic > ΔH
mic) prevailed.
The enthalpy–entropy compensation plot was found to be linear
for both copolymers. Demicellization occurred in the presence of KI
as it facilitated the buildup of water structures around the copolymer
chains. This could be verified from the increase in the cloud point,
critical micelle concentration, and free energy. Overall, the temperature
and salts inflicted a stronger hydrophobic effect upon T1304 in comparison
to T1307.
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