چکیده (انگلیسی):

The objective of the present investigation was to formulate nanoparticles constructed using
PLGA polymer for the effective targeted delivery to brain via nasal route. The PLGA
nanoparticles were optimized using novel design of experiment technique by 23 full factorial
design. Drug: polymer ratio (X1), surfactant concentration (X2) and stirring speed (X3) were
identified as critical process parameters, and its impact on particle size (Y1) and % entrapment
efficiency (Y2) was studied. The optimized nanoparticle formulation was conjugated
with glutathione as an endogenous ligand by using carbodiimide chemistry using (1-Ethyl-
3-(3-dimethylaminopropyl)carbodiimide) (EDAC) as linker molecule. From Ellman’s assay,
it was found that a total of 691.27 ± 151 units of glutathione were conjugated upon each
PLGA nanoparticle. The in vitro release studies as well as ex vivo studies revealed biphasic
pattern of drug release with initial burst release followed by slow exponential release of
drug over a period of 24 h. The in vivo biodistribution studies were conducted on rat following
nasal administration of the nanoparticle formulation (conjugated and unconjugated)
and were compared with plain paclitaxel suspension.The results clearly demonstrated that
the brain targeting efficiency was enhanced with the glutathione conjugated formulation
(387.474%) as compared to the unconjugated nanoparticle formulation (224.327%). Further,
the in vitro in vivo correlation studies revealed good relationship (R2 > 0.95) as obtained from
the levy plot. Glutathione proves to be an efficient vector for the successful transport of poor
bioavailable drug to the brain.