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 SnCl 2 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.

Intranasal Chromium Induces Acute Brain and Lung Injuries in Rats: Assessment of Different Potential Hazardous Effects of Environmental and Occupational Exposure to Chromium and Introduction of a Novel Pharmacological and Toxicological Animal Model

“…This finding suggests that a large portion of the instilled dose is absorbed through the nasal cavity and directly delivered to the brain. In correspondence, many studies showed that absorption of substances through intranasal cavity provides them a direct delivery to the brain through both the olfactory and trigeminal nerves [16]. In agreement, other research groups reported a brain-targeted distribution of manganese [25] and silver [26] following intranasal instillation.…”

“…More importantly, it has been found that a large part of these substances, absorbed nasally, could be delivered directly to the brain within minutes along both the olfactory and trigeminal nerves [16]. In animals, several metals have been shown to pass via the olfactory receptor neurons from the nasal lumen through the cribriform plate to the olfactory bulb.…”

Nicotine Modulates Cognitive Function in D-Galactose-Induced Senescence in Mice

“…Intranasal drug delivery is a novel and safe way to administer medications through the nasal mucosa (Farzampour et al, 2016 ). This route of drug administration shunts the BBB, is non-invasive and encompasses two separate pathways including trans-neuronal or immediate and para-neuronal or delayed (Mustafa et al, 2016 ). It has been shown that nicotine nasal spray improves continuous attention, working memory, and executing processing (Smith et al, 2002 ; Myers et al, 2008 ).…”

Transnasal delivery of human A-beta peptides elicits impaired learning and memory performance in wild type mice

“…Additionally, within the last years, propagation of AD pathology via a neuronal cell-to-cell transfer has been suggested by cell culture and animal experiments [ 69 , 70 ]. In transnasal delivery, however, trans-neuronal and para-neuronal pathways seem to contribute depending on the administered drug formulation [ 71 ]. As we did not investigate the spreading of the exogenously applied peptides within the brain further, we cannot speculate yet on the route taken.…”