Nose to brain delivery of drugs for CNS diseases

Zahraa Ali,Myasar Alkotaji

doi:10.33899/iphr.2021.168804

Abstract

Background: The management of central nervous system diseases is extremely challenging due to the numerous obstacles that stand against the successful delivery of drugs to their target site in the brain. Defeating the blood-brain barrier is considered the most significant challenge in this delivery. Different alternative routes of administration have been investigated. Nasal delivery is one of the possible ways for direct brain targeting. The nasal mucosa is the only part of the body at which the external environment become in straight connection with the central nervous system which takes place through the olfactory portion of the nasal mucosa. Different mechanisms have been suggested to describe the pathway for straight nasal to brain transport of medications, however, the precise route is still vague. The most important proposed pathways include nerve pathways (olfactory and trigeminal nerve), vascular, lymphatic, and cerebrospinal fluid mediated pathways. Among these mechanisms, the olfactory intra-neuronal delivery is the dominant one. Various particulate systems have been investigated for nasal delivery with the intention of direct transport to the brain. The most frequently studied delivery systems are polymeric nanosystems, lipid based nanosystems, and nanometric emulsions. In conclusion, direct nasal-to-brain delivery is a very fertile research area and any achievements in this area are running side by side with the progressions that occur in the particulate systems.

Highlights

Central nervous system (CNS) diseases are a collection of diseases that affect the central nervous systems causing a plethora of symptoms that interfere with the mental or physical status of an individual (1)
Numerous obstacles are present that need to be overcome by CNS medications in order to reach their active site in the brain
They found that the area under the curve (AUC) for the relationship between the brain concentration of the drug versus time following the intranasal administration of the liposomal formulation was much higher than the pure drug solution

Summary

Introduction

Central nervous system (CNS) diseases are a collection of diseases (including epilepsy, Alzheimer’s disease, schizophrenia, Parkinson disease, brain tumors, and others) that affect the central nervous systems causing a plethora of symptoms that interfere with the mental or physical status of an individual (1). There is a great likelihood for the drugs administered intranasally to pass directly to the brain (9) This route is brought about by the existence of olfactory neurons within the olfactory region of the nasal mucosa. It has been estimated the presence of five different delivery pathways for the transportation of the drug from the nasal cavity to the brain (32) These include the olfactory and trigeminal nerve pathways, the vascular, the lymphatic and the cerebrospinal fluid (CSF) pathways (29)(32). The olfactory intra-neuronal pathway is the primary route for the nose to brain delivery of CNS medications ( for the lipophilic drug molecules) (29). Polymerbased, lipid-based and nanometric emulsions have been explored extensively for intranasal delivery of active pharmaceutical ingredients (34)(35)

Polymeric nanosystems

Lipid-based nanoparticles

Microemulsion and nanoemulsion

Conclusions