Shiga Hideaki, Yamamoto Junpei, Miwa Takaki
Department of Otorhinolaryngology-Head and Neck Surgery, Kanazawa Medical University, Ishikawa, Japan.
Yakugaku Zasshi. 2012;132(11):1263-6. doi: 10.1248/yakushi.12-00229-3.
Nasal administration of macromolecular drugs (peptides, nanoparticles) has a possibility to enable a drug delivery system beyond the blood brain barrier via olfactory nerve transport. Basic research on nasal drug delivery to the brain has been well studied. However, evaluation of the olfactory nerve transport function in patients with olfactory disorders has yet to be done, although such an evaluation is important in selecting candidates for clinical trials. Current olfactory function tests are useful for the analysis of olfactory thresholds in olfaction-impaired patients. However, the usefulness of using the increase in olfactory thresholds in patients as an index for evaluating olfactory nerve damage has not been confirmed because of the difficulty in directly evaluating the viability of the peripheral olfactory nerves. Nasally administered thallium-201 migrates to the olfactory bulb, as has been shown in healthy volunteers. Furthermore, transection of olfactory nerve fibers in mice significantly decreases migration of nasally administered thallium-201 to the olfactory bulb. The migration of thallium-201 to the olfactory bulb is reduced in patients with impaired olfaction due to head trauma, upper respiratory tract infections, and chronic rhinosinusitis, relative to the values in healthy volunteers. Nasally administrating thallium-201 followed by single photon emission computed tomography, X-ray computed tomography and magnetic resonance imaging might be useful in choosing candidates for clinical trials of nasal drug delivery methods to the brain.
经鼻给药的大分子药物(肽、纳米颗粒)有可能通过嗅神经运输实现跨越血脑屏障的药物递送系统。鼻内给药至脑的基础研究已得到充分研究。然而,尽管这种评估对于选择临床试验候选者很重要,但尚未对嗅觉障碍患者的嗅神经运输功能进行评估。目前的嗅觉功能测试对于分析嗅觉受损患者的嗅觉阈值很有用。然而,由于难以直接评估外周嗅神经的活力,因此尚未证实将患者嗅觉阈值的升高用作评估嗅神经损伤指标的有效性。正如在健康志愿者中所显示的那样,经鼻给予铊 - 201会迁移至嗅球。此外,小鼠嗅神经纤维的横断显著降低了经鼻给予的铊 - 201向嗅球的迁移。与健康志愿者的值相比,因头部创伤、上呼吸道感染和慢性鼻窦炎导致嗅觉受损的患者中,铊 - 201向嗅球的迁移减少。经鼻给予铊 - 201后进行单光子发射计算机断层扫描、X射线计算机断层扫描和磁共振成像,可能有助于选择脑鼻内给药方法临床试验的候选者。