Pharmacokinetics and pharmacodynamics of intranasally administered selegiline nanoparticles with improved brain delivery in Parkinson's disease

Selegiline, a well-known anti-Parkinson agent, is reported to be associated with poor oral bioavailability and safety. Therefore, we formulated selegiline as chitosan nanoparticles and evaluated its pharmacokinetics and pharmacodynamics after intranasal administration to rats relative to those after oral administration. The optimized formulation exhibited spherical nanoparticles with more than 90% drug loading and steady in vitro and ex vivo drug release. Selegiline concentrations in the brain and plasma were 20- and 12-fold higher, respectively, after intranasal administration than after oral administration. Treatment with intranasal nanoparticles was also associated with better performance in locomotor activity, catalepsy, and stride length tests and significantly increased dopamine, catalase activity, and glutathione content in the brain. Therefore, intranasally administered selegiline nanoparticles holds superior therapeutic value compared to oral administration and can be a promising approach for the treatment of Parkinson's disease. Selegiline-loaded chitosan nanoparticles were prepared by ionic gelation method. Selegiline concentrations in the brain and plasma were 20- and 12-fold, respectively, higher after intranasal nanoparticles administration to rats than after oral solution administration. In the pharmacodynamic study, rotenone was administered to induce Parkinsonian symptoms in rats as confirmed by a novel modified stride length test. The intranasal administration of selegiline nanoparticles significantly improved motor performance (increased locomotor activity and reduced catalepsy) and increased brain dopamine, catalase activity, and glutathione content compared with the administration of oral solution. Intranasal nanoparticles administration is a promising approach to treat Parkinson's disease. [Display omitted]