Brain targeting by intranasal drug delivery (INDD): a combined effect of trans-neural and para-neuronal pathway

Abstract

The effectiveness of intranasal drug delivery for brain targeting has emerged as a hope of remedy for various CNS disorders. The nose to brain absorption of therapeutic molecules claims two effective pathways, which include trans-neuronal for immediate action and para-neuronal for delayed action. To evaluate the contribution of both the pathways in absorption of therapeutic molecules and nanocarriers, lidocaine, a nerve-blocking agent, was used to impair the action potential of olfactory nerve. An anti-Parkinson drug ropinirole was covalently complexes with ^99mTc in presence of SnCl₂ using in-house developed reduction technology. The radiolabeled formulations were administered intranasally in lidocaine challenged rabbit and rat. The qualitative and quantitative outcomes of neural and non-neural pathways were estimated using gamma scintigraphy and UHPLC-MS/MS, respectively. The results showed a significant (p ≤ 0.005) increase in radioactivity counts and drug concentration in the brain of rabbit and rat compared to the animal groups challenged with lidocaine. This concludes the significant contribution (p ≤ 0.005) of trans-neuronal and para-neuronal pathway in nose to brain drug delivery. Therefore, results proved that it is an art of a formulator scientist to make the drug carriers to exploit the choice of absorption pathway for their instant and extent of action.

• Brain targeting
• gamma scintigraphy
• intranasal drug delivery
• neural pathway
• non-neural pathway
• olfactory nerve
• ropinirole
• trigeminal nerve

Acknowledgements

The authors are thankful to Wockhardt Pharmaceutical (Aurangabad, India), Gattefosse (Saint Priest, Cedex France) and Nikko chemical Ltd (Tokyo, Japan) for providing ropinirole, Transcutol and sefsol 218, respectively. The authors are also grateful to Director, Institute of Nuclear Medicine and Allied Sciences for providing facilities to carry out in vivo experiments on animal models.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article. The authors are thankful to the Council for Scientific and Industrial Research (CSIR), Pusa road, New Delhi, for the grant, which supported this study.