鼻脑递送给药装置技术要点探讨及监管考量

Nasal Delivery Device for “Nose-to-Brain”: Technical Discussion and Regulatory Considerations

关键词:  鼻脑递送  给药装置  喷雾形态  靶向递送

Key words:  nose-to-brain delivery  drug delivery device  spray form  targeted delivery

摘要:

针对越来越迫切的脑部疾病治疗需求，鼻脑递送技术利用鼻腔与脑组织间特殊的生理连接，避开血脑屏障、肝脏首过效应等生理因素，采用非侵入性给药方式将治疗脑部疾病的药物直接递送入脑，发挥治疗作用，为解决日益严重的脑部疾病问题提供了新的可能。本文在分析鼻脑递送生理特点和优势的基础上，重点梳理了近年来鼻脑递送给药装置方面的最新研究进展，探讨此类特殊装置的技术关键点，并结合国内外研发及产业现状提出监管考量，以期为鼻脑递送技术的深入发展和更为广阔的应用提供建议。

Abstract:

According to the differences in function and structure, the nasal cavity can be roughly divided into three regions:the vestibule, respiratory zone, and olfactory zone. The current mainstream of research believes that the process of drugs entering the brain through the nasal cavity mainly occurs in the latter two regions, with the olfactory zone being the primary area. To allow more effective ingredients to enter the brain or reach the above-mentioned delivery pathway targets quickly, when developing related drug products, it should be possible to deliver the drug to the upper nasal cavity, like the upper respiratory zone and olfactory zone. Therefore, special drug delivery devices that can target the upper nasal cavity play a key and core role in Nose-to-Brain delivery.
It is nasal spray device Nose-to-Brain delivery products approved by FDA mainly use. The following are three main research directions of the Nose-to-Brain delivery devices. 1) In-depth assessment and research of critical quality attributes and their influencing factors. Many research institutions and enterprises have conducted extensive research on liquid or powder sprays aided by nasal spray devices, and it is currently agreed that spray pattern, plume geometry, and particle size are the critical quality attributes, which can be mainly affected by spray devices and content properties. A spray with a smaller angle can penetrate the nasal valve easier and deliver to the upper nasal cavity. 2) The study of delivery platforms for such complex drug-device combinations is also a key direction, such as Exhalation Delivery Systems (EDS), Precision Olfactory Delivery Systems (POD®), and Controlled Particle Dispersion Technology (CPD) platforms, etc., which are general technology platforms established by drug delivery device manufacturers to better achieve Nose-to-Brain delivery. They have indeed achieved more accurate drug delivery, more significant therapeutic effects, and more convenient use for patients. 3) Combining drug delivery devices with new technologies. For example, adding mucosal adsorbents and permeation enhancers to the prescription, and preparing medicinal products using nanoparticle formulation technology. It is new directions for future research and development which can further meet the needs of Nose-to-Brain delivery.
Nose-to-Brain delivery bring new hope to a wide range of clinical needs for brain diseases due to its special advantages. In order to play the truly important role of Nose-to-Brain delivery, it is not only the industry make efforts in research and industrialization, but also regulatory aspects need scientific evaluation and reasonable regulation of emerging technologies. Here are our thoughts. First, we need to pay attention to the important role of regulatory science in the technical research and evaluation of Nose-to-Brain delivery products. Next, we need to pay attention to the interaction and collaboration between scientific researchers, industry, regulators, and users. Then, regulatory authorities needs to broaden its thinking flexibility and attach importance to the role of individual drug guidelines, summary key technical points and solutions from multiple cases. Finally, we need to pay attention to the design, research and development support, and industrialization security of domestic drug delivery devices.