By Ram Rao, Ph.D., Principal Research Scientist for Apollo Health

In the Indian system of medicine called Ayurveda, practitioners rely on novel methods of administering therapeutic agents to treat brain disorders. One such method, called ‘NASYA’ involves intranasal administration of dry herbal powders, aqueous-based herbal extracts, or medicated oils. This intranasal delivery method is a practical, non-invasive, rapid, and simple method to deliver the therapeutic agent into the brain. And we now know why! 

The blood-brain barrier (BBB) is a boundary between the circulating blood and the brain’s extracellular space. The BBB is highly restrictive and allows only selective substances to cross from the systemic circulation (bloodstream) into the brain. This barrier is needed to protect the brain from toxins, pathogens, and other circulating chemicals that can potentially damage the nerve cells’ structure and/or function. The components that can pass through the barrier are water, gases like oxygen, and fat-soluble substances. While the BBB is essential for normal brain structure and function, its presence has prevented the entry of many therapeutic agents for treating brain-related diseases and injuries, including but not limited to Alzheimer’s disease, strokes, brain tumors, and head injuries. Thus the challenge for the drug industry with respect to neurodegenerative diseases is to design and select drug candidates that can pass through the BBB, bind to specific targets, and modify the disease condition effectively. 

Intranasal administration works successfully because of a lack of an effective barrier between the nasal cavity and the brain’s olfactory region. Thus, compounds introduced into the nasal cavity bind to specific receptors lining this route and get transported into the brain. A wide variety of therapeutic agents, including large-sized molecules, small molecules, and macromolecules, can be rapidly delivered into the brain using this method, thereby reducing systemic exposure and side effects. Intranasal administration offers numerous benefits for drug delivery into the brain, and interest in this non-invasive route of administration has increased. Researchers are now successfully using this route to administer peptides, proteins, functional siRNA, stem cells, and other biologics directly into the brain. Several forms of commercially available insulin are being atomized into a spray and administered intranasally to treat cognitive impairment and dementia. This route of administration avoids the unwanted effect of increasing systemic insulin levels, which could lead to hypoglycemia or insulin resistance.

As more drug discovery researchers become aware of this novel delivery route, the type and list of substances that get delivered into the brain via the nasal cavity will only continue to expand. While current research confirms the intranasal delivery route as exciting and novel, further investigation is warranted to understand the mechanism, stability, potency, distribution, and efficacy of drugs administered intranasally to utilize this approach as an effective therapeutic strategy for diseases of the brain. 

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