Blood-Brain Barrier (BBB) acts as a highly impermeable barrier, presenting an impediment to the crossing of most classical drugs targeted for neurodegenerative diseases including Parkinson's disease (PD). About the nature of drugs and other potential molecules, they impose unavoidable doserestricted limitations eventually leading to the failure of therapy. However, many advancements in formulation technology and modification of delivery approaches have been successful in delivering the drug to the brain in the therapeutic window. The nose to the brain (N2B) drug delivery employing the nanoformulation, is one such emerging delivery approach, overcoming both classical drug formulation and delivery-associated limitations. This latter approach offers increased bioavailability, greater patient acceptance, lesser metabolic degradation of drugs, circumvention of BBB, ample drug loading along with the controlled release of the drugs. In N2B delivery, the intranasal (IN) route carries therapeutics firstly into the nasal cavity followed by the brain through olfactory and trigeminal nerve connections linked with nasal mucosa. The N2B delivery approach is being explored for delivering other biologicals like neuropeptides and mitochondria. Meanwhile, this N2B delivery system is associated with critical challenges consisting of mucociliary clearance, degradation by enzymes, and drug translocations by efflux mechanisms. These challenges finally culminated in the development of suitable surfacemodified nano-carriers and Focused- Ultrasound-Assisted IN as FUS-IN technique which has expanded the horizons of N2B drug delivery. Hence, nanotechnology, in collaboration with advances in the IN route of drug administration, has a diversified approach for treating PD. The present review discusses the physiology and limitation of IN delivery along with current advances in nanocarrier and technical development assisting N2B drug delivery.

中文翻译：

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纳米技术进步从鼻子到大脑输送治疗药物以改善帕金森病治疗

血脑屏障 (BBB) 是一种高度不可渗透的屏障，阻碍了大多数针对神经退行性疾病（包括帕金森病 (PD)）的经典药物的通过。关于药物和其他潜在分子的性质，它们施加了不可避免的剂量限制，最终导致治疗失败。然而，制剂技术的许多进步和递送方法的修改已成功地将药物在治疗窗口内递送至大脑。采用纳米制剂的鼻到脑（N2B）药物递送是一种新兴的递送方法，克服了传统药物制剂和递送相关的限制。后一种方法提供了更高的生物利用度、更高的患者接受度、更少的药物代谢降解、规避血脑屏障、充足的药物负载以及药物的受控释放。在 N2B 递送中，鼻内 (IN) 途径首先将治疗药物输送到鼻腔，然后通过与鼻粘膜相连的嗅觉和三叉神经连接输送到大脑。N2B 递送方法正在探索用于递送神经肽和线粒体等其他生物制品。同时，这种 N2B 递送系统面临着一些关键挑战，包括粘膜纤毛清除、酶降解以及外排机制引起的药物易位。这些挑战最终导致了合适的表面改性纳米载体和聚焦超声辅助 IN（FUS-IN 技术）的开发，扩大了 N2B 药物输送的视野。因此，纳米技术与 IN 给药途径的进步相结合，提供了治疗 PD 的多样化方法。本综述讨论了 IN 递送的生理学和局限性，以及协助 N2B 药物递送的纳米载体和技术开发的当前进展。