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Drug Deliv. 2016;23(3):933-9. doi: 10.3109/10717544.2014.923064. Epub 2014 Jun 24.

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

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a Department of Pharmaceutics, Faculty of Pharmacy , Hamdard University , New Delhi , India .
b College of pharmacy, Al-Dawadmi Campus, Shaqra University , Riyadh , Kingdom of Saudi Arabia .
c Department of Nuclear Medicine Division (NMD) , Institute of Nuclear Medicine & Allied Sciences , Timarpur , Timarpur , Delhi , India , and.
d Department of Pharmacy , Oman Medical College , Azaiba , Muscat , Sultanate of Oman.


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 (99m)Tc 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

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