卡巴马泽和基基-β-环氧的含有复合物通过提高溶解度来增强鼻至大脑的输送
Takuhiro Totoki1, Koki Ogawa1, Tetsuya Ozeki1
1Drug Delivery and Nano Pharmaceutics, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan.
概括
propyl-β-cyclodextrin (HP-βCD) 纳入复合物增强卡巴马西 (CBZ) 溶解性,改善鼻至脑药物输送. 与传统方法相比,这种方法显著提高了大脑的吸收率.
科学领域:
- 制药科学 制药科学
- 药物运输 药物运输 药物运输
- 神经科学是一个神经科学.
背景情况:
- 鼻内药物输送绕过血脑屏障进行非侵入性大脑输送.
- 水溶性较差的药物在鼻腔中面临溶性限制,阻碍大脑的输送.
- 卡巴马西平 (CBZ) 是一种水溶性较差的药物,有可能通过鼻内输入大脑.
研究的目的:
- 开发一种含有碳二 (CBZ) 的基烯-β-循环二 (HP-βCD) 纳入复合物.
- 为了提高CBZ的溶解度,并促进其鼻到脑的输送.
- 通过鼻内给药来评估CBZ/HP-βCD复合物的脑吸收和分布.
主要方法:
- 阶段溶解性分析和乔布的图表来确认复合形成 (1:1 CBZ:HP-βCD).
- 使用冷干燥和喷雾冷干燥制备粉末配方.
- 粉末溶解,稳定性和无形状态的评估.
- 在老鼠的鼻腔内给药,以比较CBZ/HP-βCD复合体粉末与CBZ散装药物或物理混合物的脑吸收.
- 分析大脑与血的比例和区域大脑分布.
主要成果:
- 成功地形成了CBZ与HP-βCD的1:1纳入复合体.
- 粉末配方在5分钟内完全溶解,并保持无形状态.
- 在大鼠中,CBZ/HP-βCD复合物粉末的鼻内注射显著增加了大脑吸收.
- 粉末配方的脑血比液体配方的脑血比率更高,这表明鼻子到大脑的直接运输得到了增强.
- 在嗅球中观察到主要的药物积累,与鼻腔附近一致.
结论:
- HP-βCD纳入复杂化是一种可行的策略,可以提高CBZ等溶解不良药物的可溶性和稳定性.
- 通过鼻内输送CBZ/HP-βCD复合物粉末,可以提高脑部输送效率.
- 观察到的嗅球积累突出了针对大脑深层区域的潜在限制,需要进一步优化.
- 这种方法对通过鼻内注射输送难溶的中枢神经系统活性药物充满希望.
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