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

Drug Delivery

Aseem Bhatnagar¹  Javed Ali²  Sanjula Baboota²  Abdulmohsen H. Alrohaimi³  Gulam Mustafa³  Alka Ahuja⁴ 

[1] Department of Nuclear Medicine Division (NMD), Institute of Nuclear Medicine & Allied Sciences, Timarpur, Timarpur, Delhi, India, an;Department of Pharmaceutics, Faculty of Pharmacy, Hamdard University, New Delhi, India;Department of Pharmaceutics, Faculty of Pharmacy, Hamdard University, New Delhi, India;College of pharmacy, Al-Dawadmi Campus, Shaqra University, Riyadh, Kingdom of Saudi Arabia;Department of Pharmacy, Oman Medical College, Azaiba, Muscat, Sultanate of Oma;

关键词: Brain targeting;    gamma scintigraphy;    intranasal drug delivery;    neural pathway;    non-neural pathway;    olfactory nerve;    ropinirole;    trigeminal nerve;   

DOI  :  10.3109/10717544.2014.923064

来源: publisher

【 摘 要 】

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.

【 授权许可】

Unknown