Brain targeted delivery of mucoadhesive thermosensitive nasal gel of selegiline hydrochloride for treatment of Parkinson's disease

Abstract

Selegiline hydrochloride (SL), is an anti-Parkinson’s agent, has low-oral bioavailability due to its high first pass metabolism and scarce oral absorption. In the present study, SL mucoadhesive nasal thermosensitive gel (SNT-gel) was prepared to enhance the bioavailability and subsequently, its concentration in the brain. The SNT-gel was prepared using Poloxamer 407-Chitosan combination and optimised formulation was further evaluated for physicochemical parameters. The comparative pharmacodynamic studies including behavioural studies, biochemical testing and histopathology of the brain was carried out in rats for SNT-gel, SL-nasal solution and SL Marketed Tablets. The optimised SNT-gel formulation (SNT-V) revealed sol-gel transition at 33–34°C. In-vitro diffusion study of SNT-V showed 102.37 ± 2.1% diffusion at 12 h which reduced to 89.64 ± 1.2% in Ex-vivo diffusion. Comparative results of behavioural studies indicated an improved score of photoactometer and reduced motor deficit (catalepsy score) in SNT-gel treatment group as compared with other groups. Similarly, a significant increase in brain dopamine, reduction in monoamine oxidase B level, increase in catalase activity and level of reduced glutathione upon treatment with SNT-gel indicated its effectiveness which was also supported by histopathology results. Therefore, nasal thermosensitive gel holds better potential for brain targeting in Parkinson’s disease over the conventional nasal or oral formulations.

Keywords:

• Brain targeting
• selegiline hydrochloride
• nasal thermosensitive gel
• Parkinson’s disease
• behavioural studies
• biochemical testing

Acknowledgements

This work was supported by the CSIR, New Delhi, India [Grant number: 27(296)/13-EMR-II]. The authors are thankful to CSIR, India for funding this research work and Mr. Vinay Sridhar for the award of senior research fellowship under this research scheme. Also, authors are thankful to Anton Paar India Pvt. Ltd. for support in viscosity studies and Tack test.

Disclosure statement

The authors report no conflicts of interest.

Additional information

Funding

This work was supported by the CSIR, New Delhi, India [Grant number: 27(296)/13-EMR-II].