Nose to Brain Targeting Potential of a Chitosan-Coated Nano-Formulation: Pharmacodynamic and Pharmacoscintigraphic Evaluation

摘要

Ropinirole, a non-ergoline dopamine agonist has considerable neuroprotective property and is extensively used in both monotherapy as well as in combination therapy for the treatment of Parkinson's disease. It is also being used in restless leg night syndrome and in levodopa associated dyskinesia. Its low brain bioavailability and high systemic side effects limit its neurotherapeutic potential. A homogenized chitosan coated mucoadhesive ropinirole nanoemulsion (o/w) was prepared using the minimum possible amount of surfactant that could improve its solubility, stability and intransnasal flux. The homogenized chitosan coated mucoadhesive nanoemulsion was evaluated on the basis of drug release, globule size, viscosity, polydispersity, zeta potential and surface morphology. Technetium (~(99m)Tc) labeled ropinirole nanoemulsion and conventional solution were administered intranasally in Sprague-Dawley for dynamic imaging to visualize the nose to brain pathway. In distribution studies, an insignificant ropinirole level was detected in the systemic organs including liver, heart, spleen, lungs, kidney and significantly high levels were detected in brain with significant increase in the AUC, t_(1/2) and MRT. In the second set of experiment haloperidol was used for inducing Parkinson's related symptoms. Treatment with formulation showed better pharmcodynamic response compared to other formulations tested.