Exploring Nose to Brain Nano Delivery for Effective Management of Migraine

Abstract

Migraine is a disabling disease, characterized by severe throbbing headache. Patients demand quick relief from this pain. The presence of blood brain barrier does not permit the drug to penetrate the brain effectively. Administration of conventional anti-migraine medications via oral route leads to erratic absorption of drugs. Delayed gastric emptying is also responsible for ineffective absorption of drug. Migraine induced nausea and vomiting, further limits patient compliance to oral medication. Other limitations associated with oral route include extensive first pass metabolism, slow onset of action, inability to cross blood brain barrier and requirement of large amount of dose/dosage and frequent administration. The anti-migraine drugs used in migraine like triptans are therapeutically effective but have low bioavaialability on oral administration. Also, these drugs are associated with several cardiovascular complications. The oral dose of most antimigraine drugs oral tritpans, Ergot amine, NSAIDs and CGRP antagonist is quite high because of their poor bioavailability. As a result of these drugs are associated with several side effects. This aspects necessitates the need of developing a dosage form that can deliver drug directly brain thereby reducing the dose. Use of invasive techniques to deliver these therapeutics to the brain do exist, however, they are painful, require expert assistance and are not cost-effective approach for migraine treatment. These limitations demand development of a novel non-invasive approach that is safe, efficacious and has high patient compliance. As, reported it is possible to target the brain tissue by administering the drug intranasally using olfactory and the trigeminal pathway. This route is non-invasive, avoids first-pass metabolism, eliminates nausea and vomiting, helps reduce dose, and thus helps achieve increase patient compliance. Some factors like solubility, lipophilicity of the drug, mucociliary clearance, enzymatic degradation hinder the bioavailability of the drug by nasal route. Therefore, there is a grave need to develop novel nasal formulations with prolonged nasal residence time, which can modulate pharmacokinetics for adequate therapeutic response, and render efficient yet robust brain targeting. It is necessary to consider these challenges in developing efficient intranasal dosage form. This review gives a brief overview of all the novel carriers reported for improving the treatment of migraine. Nanocarrier based delivery systems like in-situ gels, micro emulsion, nanoemulsion, nanoparticles, vesicular systems, micelles, and microspheres used in nose to brain delivery of migraine therapeutics are also discussed in the article.

Gel-forming antagonist provides a lasting effect on CGRP-induced vasodilation

“…For example, the EC (90) for telcagepant to inhibit the capsaicin-induced increase in dermal blood flow was ∼909 nM ( Sinclair et al, 2010 ). Therefore, the limited efficacy of small molecule antagonists could be due to restricted bioavailability in target tissues or their specificity for select signaling states ( Goadsby et al, 2020 ; Ailani et al, 2021 ; Croop et al, 2021 ; Altamura et al, 2022 ; Tanna et al, 2022 ). Because the gel-forming peptide antagonists are expected to block receptor activation via a distinct and larger interface compared to small molecule antagonists ( Lee et al, 2016 ), we speculate that the gel-forming antagonists could have a pharmacodynamic characteristic distinct from that of gepant therapies.…”

Research progress in brain-targeted nasal drug delivery

“…Usually, drugs with high lipid solubility have good compatibility with the nasal mucosa and are more likely to be absorbed. However, the high fat solubility of a drug can also be detrimental as it can facilitate entry into the general circulation after absorption through the nasal cavity, which is not conducive for drug entry into the brain ( Chen et al, 2022 ; Tanna et al, 2023 ).…”

Acute seizure therapies in people with epilepsy: Fact or fiction? A U.S. Perspective

“…The potential shortcomings of orally administrated tablets and oral formulations include aspiration risk, delayed time to efficacy, first-pass metabolism, and incomplete ingestion limited by swallowing [8] , [44] , [45] . Furthermore, delayed absorption may occur when taken with food [46] .…”