Department of Pharmaceutics, University of Washington, Seattle, 98195-7610, USA.
AAPS PharmSciTech. 2011 Jun;12(2):534-43. doi: 10.1208/s12249-011-9614-1. Epub 2011 Apr 26.
Many nasally applied compounds gain access to the brain and the central nervous system (CNS) with varying degree. Direct nose-to-brain access is believed to be achieved through nervous connections which travel from the CNS across the cribriform plate into the olfactory region of the nasal cavity. However, current delivery strategies are not targeted to preferentially deposit drugs to the olfactory at cribriform. Therefore, we have developed a pressurized olfactory delivery (POD) device which consistently and non-invasively deposited a majority of drug to the olfactory region of the nasal cavity in rats. Using both a hydrophobic drug, mannitol (log P = -3.1), and a hydrophobic drug, nelfinavir (log P = 6.0), and POD device, we compared brain and blood levels after nasal deposition primarily on the olfactory region with POD or nose drops which deposited primarily on the respiratory region in rats. POD administration of mannitol in rats provided a 3.6-fold (p < 0.05) increase in cortex-to-blood ratio, compared to respiratory epithelium deposition with nose drop. Administration of nelfinavir provided a 13.6-fold (p < 0.05) advantage in cortex-to-blood ratio with POD administration, compared to nose drops. These results suggest that increasing the fraction of drug deposited on the olfactory region of the nasal cavity will result in increased direct nose-to-brain transport.
许多经鼻腔给予的化合物以不同程度进入大脑和中枢神经系统 (CNS)。人们认为，直接的鼻脑通路是通过从 CNS 穿过筛板进入鼻腔嗅区的神经连接实现的。然而，目前的给药策略并不是针对将药物优先递送到嗅裂。因此，我们开发了一种加压嗅觉给药 (POD) 装置，该装置可在大鼠的鼻腔嗅区持续且非侵入性地递大部分药物。使用亲脂性药物甘露醇（log P = -3.1）和亲脂性药物奈非那韦（log P = 6.0）和 POD 装置，我们比较了鼻内给药后主要沉积在嗅裂区的 POD 或滴鼻与主要沉积在呼吸区的 POD 或滴鼻在大鼠中的脑和血药水平。与经鼻滴注呼吸上皮相比，POD 给药在大鼠中的甘露醇给药可使皮质/血液比增加 3.6 倍（p < 0.05）。与鼻滴注相比，POD 给药可使奈非那韦的皮质/血液比增加 13.6 倍（p < 0.05）。这些结果表明，增加药物在鼻腔嗅区的沉积分数将导致直接鼻脑转运增加。
