Background:
Selegiline hydrochloride, a hydrophilic anti-Parkinson’ moiety, undergoes extensive
first-pass metabolism and has low bioavailability. A process to obtain of selegiline (SH) loaded chitosan
nanoparticles was attempted to circumvent the above problem, through intranasal delivery.
Methods:
SH loaded polymeric nanoparticles were prepared by ionic gelation of chitosan with
tripolyphosphate, and stabilized by tween 80/ poloxamer 188. The resulting nanoparticles (NPs) were
characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry, entrapment
efficiency, particle size, zeta potential and surface morphology by scanning electron microscopy. Further, they
were schematically evaluated for mucoadhesive strength, in-vitro drug release, release kinetics,
pharmacokinetics, catalepsy, akinesia, in-vivo lipid peroxidation, nitrite levels, glutathione, catalase enzyme
levels in brain and physicochemical stability parameters.
Results:
Selegiline nanoparticles (SP18) produced were in size of 63.1 nm, polydispersity index of 0.201, zeta
potential of +35.2 mV, mucoadhesion of 65.4% and entrapment efficiency of 74.77%. Selegiline showed biphasic
release from nanoparticles, over a period of 36 h, with Fickian diffusion controlled release profile. Maximum
concentration of SH in plasma was recognized as 52.71 ng/ml at 2 h for SP18, 20.09 ng/ml at 1 h for marketed
formulation, and 21.69 ng/ ml for drug solution. SH loaded NPs showed a reversive effect in catalepsy and akinesia
behaviour. This effect was especially pronounced in rats receiving SH loaded CS-NPs. Significant decrease in lipid
peroxidation and nitrite concentration; increase in reduced glutathione and catalase enzyme levels were obtained
due to antioxidant characteristics of SH, which turned to be useful to treat Parkinson’s disease.
Conclusion:
Selegiline loaded chitosan nanoparticles form an effective non-invasive drug delivery
system of direct nose to brain targeting in Parkinson’s disease.
