Tanna Vidhi, Sawarkar Sujata P, Ravikumar Padmini
Department of Pharmaceutics, SVKM's Dr. Bhanuben Nanavati College of Pharmacy, University of Mumbai, Mumbai, India.
Curr Drug Deliv. 2023;20(2):144-157. doi: 10.2174/1567201819666220401091632.
Migraine is a disabling disease characterized by severe throbbing headaches. Patients demand quick relief from this pain. The presence of the 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 the ineffective absorption of the drug. Migraine-induced nausea and vomiting further limit patient compliance to oral medication. Other limitations associated with the oral route include extensive first-pass metabolism, slow onset of action, inability to cross the blood-brain barrier, requirement of a large amount of dose/dosage, and frequent administration. The anti-migraine drugs used in migraine, such as triptans, are therapeutically effective but have low bioavailability on oral administration. Also, these drugs are associated with several cardiovascular complications. The oral dose of most antimigraine drugs, oral triptans, Ergotamine, NSAIDs, and CGRP antagonists is quite high because of their poor bioavailability. As a result, these drugs are associated with several side effects. This aspect necessitates the need to develop a dosage form that can deliver drugs directly to the brain, thereby reducing the dose. Invasive techniques to deliver these therapeutics to the brain do exist. However, they are painful, require expert assistance, and are not a cost-effective approach for migraine treatment. These limitations demand the development of a novel non-invasive approach that is safe, efficacious, and has high patient compliance. According to reports, it is possible to target the brain tissue by administering the drug intranasally using the 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 increased patient compliance. Some factors like solubility, the lipophilicity of the drug, mucociliary clearance, and 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. Considering these challenges, developing an efficient intranasal dosage form is necessary. 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, microemulsion, nanoemulsion, nanoparticles, vesicular systems, micelles, and microspheres used in nose to brain delivery of migraine therapeutics are also discussed in the article.
偏头痛是一种使人衰弱的疾病，其特征为严重的搏动性头痛。患者渴望迅速缓解这种疼痛。血脑屏障的存在使得药物无法有效穿透进入大脑。通过口服途径给予传统的抗偏头痛药物会导致药物吸收不稳定。胃排空延迟也会导致药物吸收无效。偏头痛引起的恶心和呕吐进一步限制了患者对口服药物的依从性。与口服途径相关的其他局限性包括广泛的首过代谢、起效缓慢、无法穿过血脑屏障、需要大量剂量以及频繁给药。用于治疗偏头痛的抗偏头痛药物，如曲坦类药物，在治疗上是有效的，但口服给药时生物利用度较低。此外，这些药物还与多种心血管并发症相关。由于生物利用度差，大多数抗偏头痛药物、口服曲坦类药物、麦角胺、非甾体抗炎药和降钙素基因相关肽（CGRP）拮抗剂的口服剂量相当高。因此，这些药物会产生多种副作用。这就需要开发一种能够将药物直接输送到大脑的剂型，从而降低剂量。确实存在将这些治疗药物输送到大脑的侵入性技术。然而，它们很痛苦，需要专业人员协助，而且对于偏头痛治疗来说并不是一种经济有效的方法。这些局限性要求开发一种新型的非侵入性方法，该方法安全、有效且患者依从性高。据报道，通过嗅觉和三叉神经途径经鼻给药有可能靶向脑组织。这种途径是非侵入性的，可避免首过代谢，消除恶心和呕吐，有助于减少剂量，从而提高患者依从性。一些因素，如药物的溶解度、亲脂性、黏液纤毛清除和酶降解，会阻碍药物经鼻途径的生物利用度。因此，迫切需要开发具有延长鼻腔滞留时间的新型鼻腔制剂，其可以调节药代动力学以获得充分的治疗反应，并实现高效且稳定的脑靶向。考虑到这些挑战，开发一种高效的鼻腔剂型是必要的。本综述简要概述了为改善偏头痛治疗而报道的所有新型载体。本文还讨论了用于偏头痛治疗药物鼻脑递送的基于纳米载体的递送系统，如原位凝胶、微乳、纳米乳、纳米颗粒、囊泡系统、胶束和微球。
