Md Shadab, Mustafa Gulam, Baboota Sanjula, Ali Javed
a Department of Pharmaceutical Technology , School of Pharmacy, International Medical University (IMU) , Kuala Lumpur , Malaysia .
b College of Pharmacy, Al-Dawadmi Campus, Shaqra University , Riyadh , Kingdom of Saudi Arabia , and.
Drug Dev Ind Pharm. 2015;41(12):1922-34. doi: 10.3109/03639045.2015.1052081. Epub 2015 Jun 9.
Brain disorders remain the world's leading cause of disability, and account for more hospitalizations and prolonged care than almost all other diseases combined. The majority of drugs, proteins and peptides do not readily permeate into brain due to the presence of the blood-brain barrier (BBB), thus impeding treatment of these conditions.
Attention has turned to developing novel and effective delivery systems to provide good bioavailability in the brain.
Intranasal administration is a non-invasive method of drug delivery that may bypass the BBB, allowing therapeutic substances direct access to the brain. However, intranasal administration produces quite low drug concentrations in the brain due limited nasal mucosal permeability and the harsh nasal cavity environment. Pre-clinical studies using encapsulation of drugs in nanoparticulate systems improved the nose to brain targeting and bioavailability in brain. However, the toxic effects of nanoparticles on brain function are unknown.
This review highlights the understanding of several brain diseases and the important pathophysiological mechanisms involved. The review discusses the role of nanotherapeutics in treating brain disorders via nose to brain delivery, the mechanisms of drug absorption across nasal mucosa to the brain, strategies to overcome the blood brain barrier, nanoformulation strategies for enhanced brain targeting via nasal route and neurotoxicity issues of nanoparticles.
脑部疾病仍然是全球致残的主要原因,其导致的住院治疗和长期护理比几乎所有其他疾病的总和还要多。由于血脑屏障(BBB)的存在,大多数药物、蛋白质和肽不易渗透到大脑中,从而阻碍了这些疾病的治疗。
人们已将注意力转向开发新型有效的给药系统,以在大脑中提供良好的生物利用度。
鼻内给药是一种非侵入性给药方法,可绕过血脑屏障,使治疗物质直接进入大脑。然而,由于鼻粘膜通透性有限和鼻腔环境恶劣,鼻内给药在大脑中产生的药物浓度相当低。在临床前研究中,将药物包裹在纳米颗粒系统中可改善从鼻腔到大脑的靶向性以及大脑中的生物利用度。然而,纳米颗粒对脑功能的毒性作用尚不清楚。
本综述着重阐述了对几种脑部疾病以及所涉及的重要病理生理机制的理解。该综述讨论了纳米治疗剂通过鼻腔到大脑给药治疗脑部疾病的作用、药物从鼻粘膜吸收到大脑的机制、克服血脑屏障的策略、通过鼻腔途径增强大脑靶向性的纳米制剂策略以及纳米颗粒的神经毒性问题。