Overcoming Parkinson’s disease: direct nose-to-brain delivery of amantadine

Lungare, Shital; Bowen, James and Badhan, Raj Kumar Singh (2013). Overcoming Parkinson’s disease: direct nose-to-brain delivery of amantadine. In: UK & Ireland Controlled Release Society Annual Symposium, 16 Apr 2013, Reading, UK.

URL: https://www.academia.edu/9851877/Overcoming_Parkin...


Treatments for Parkinson’s disease face significant challenges in delivery to the due to the presence of blood brain barrier (BBB). The aim of this study was to develop and characterise an in-situ thermoresponsive polymer based gel system for possible exploitation of the intranasal olfactory route where the BBB is absent. Reaching the olfactory region in the nasal cavity and mucociliary clearance are the main hurdles from formulation point of view. Thermo-sensitive and pH sensitive polymers seem to be the answer to these problems. Formulation made with these polymers along with mucoadhesives will be liquid at room temperature and will turn into a viscous gel when comes in contact with the body either due to change in pH or temperature. We have successfully prepared the gels using cold method using amantadine, with Pluronic F127 as a thermoreversible polymer and carboxymethylcelluose (CMS) as a mucoadhesive polymer. Rheological characterisation confirmed the sol-to-gel phenomenon at desired temperatures. CMC increased the gelation temperature with increase in concentration, whereas amantadine lowered the gelation temperature with increase in concentration. After preliminary studies, 16 % of Pluronic F127 found to be a suitable concentration for the formulation to change from sol-to-gel at ambient nasal temperatures. Molecular, gene expression and drug transport studies using the nasal epithelial cell lines RPMI 2650 are also under investigation along with the development of an in-vitro olfactory-epithelial cell culture model to study axonal transport. Unlike the animal studies this model will be faster to use, efficient and also better representation of human olfactory system.

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