title: 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 (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.
authors: 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 .
authors: Gulam
authors: G
authors: Mustafa
authors: 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 .
authors: Abdulmohsen H
authors: AH
authors: Alrohaimi
authors: c Department of Nuclear Medicine Division (NMD) , Institute of Nuclear Medicine & Allied Sciences , Timarpur , Timarpur , Delhi , India , and.
authors: Aseem
authors: A
authors: Bhatnagar
authors: a Department of Pharmaceutics, Faculty of Pharmacy , Hamdard University , New Delhi , India .
authors: Sanjula
authors: S
authors: Baboota
authors: a Department of Pharmaceutics, Faculty of Pharmacy , Hamdard University , New Delhi , India .
authors: Javed
authors: J
authors: Ali
authors: d Department of Pharmacy , Oman Medical College , Azaiba , Muscat , Sultanate of Oman.
authors: Alka
authors: A
authors: Ahuja
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations / Q000008:administration & dosage; D016503:Drug Delivery Systems / Q000379:methods*; D008012:Lidocaine / Q000008:administration & dosage; D008297:Male; D009297:Nasal Mucosa / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D011817:Rabbits; D051381:Rats
chemical_list: D003692:Delayed-Action Preparations; D008012:Lidocaine
keywords: Brain targeting; gamma scintigraphy; intranasal drug delivery; neural pathway; non-neural pathway; olfactory nerve; ropinirole; trigeminal nerve