Intranasal delivery: An attractive route for the administration of nucleic acid based therapeutics for CNS disorders

Abstract

The etiologies of several cardiovascular, inflammatory, neurological, hereditary disorders, cancer, and infectious diseases have implicated changes in the genetic set up or genetic mutations as the root cause. Nucleic acid based therapeutics (NBTs) is a new class of biologics that are known to regulate gene expression at the transcriptional and post-transcriptional level. The NBTs include oligonucleotides, nucleosides, antisense RNA, small interfering RNAs, micro RNA etc. In recent times, this new category of biologics has found enormous potential in the management of cardiovascular, inflammatory, neurological disorders, cancer, infectious diseases and organ transplantation. However, the delivery of NBTs is highly challenging in terms of target specificity (intracellular delivery), mononuclear phagocyte system uptake, stability and biodistribution. Additionally, management of the above mentioned disorders require regular and intrusive therapy making non-invasive routes preferable in comparison to invasive routes like parenteral. The nasal route is garnering focus in delivery of NBTs to the brain in the management of several CNS disorders due to the associated merits such as non-invasiveness, possibility of chronic delivery, improved patient compliance, avoidance of hepatic and gastrointestinal metabolism as well as ability to bypass the BBB. Hence in recent times, this route has been sought by the reserachers as an alternative to parenteral therapy for the delivery of several NBTs. This review shall focus on an array of NBTs delivered through nasal route, their challenges, applications and opportunities. The novel delivery systems for incorporating NBTs; their targeting strategies shall be critically reviewed. The challenges towards regulatory approvals and commercialization shall also be discussed at large. Comparison of learnings derived from the success and barriers in nasal delivery of NBTs will help in identification of futuristic opportunities for their translation from bench to bedside.

Enolase inhibitors as therapeutic leads forNaegleria fowleriinfection

“…The success of the HEX treatment may be in part due to direct transport of the agent to the brain, which would reduce the impact of dilution by distribution (37). Direct transport can result from endocytosis by olfactory sensory cells followed by exocytosis into the synaptic clefts in the olfactory bulb, which would introduce HEX into the CNS in a position to interact with invading amoebae at the site of brain infection (38).…”

mRNA nanodelivery systems: targeting strategies and administration routes

“…However, as mentioned in the previous chapter, mRNA NPs administered intranasally still need to overcome the barriers in the respiratory tract to reach the deep lung. Moreover, the latest research found that intranasal administration can bypass the BBB and reach the central nervous system through the sense of smell and trigeminal nerve, which provides a novel approach for brain or nerve treatment [ 283 , 284 ].…”

Effects of Nozzle Retraction Elimination on Spray Distribution in Middle-Posterior Turbinate Regions: A Comparative Study

“…Additionally, the nasal route is appealing for needle-free vaccinations and systemic medication delivery, which is especially valued for its rapid absorption and immediate effects [6]. These devices exemplify the shift toward intranasal administration as a compelling alternative to oral and injectable routes, with the nasal mucosa emerging as a promising conduit for systemic drug delivery [7,8]. The utility of nasal sprays in administering influenza vaccines underscores their potential in delivering treatments directly to areas rich in ACE2 receptors, such as the posterior two-thirds of the nose and nasopharynx, which is crucial for effective mucosal immunization against respiratory infectious pathogens like SARS-CoV-2 [9][10][11].…”