Drug Delivery to Respiratory Mucosa using Fusogenic Liposomes and its Molecular Design.

使用融合脂质体将药物输送至呼吸道粘膜及其分子设计。

• 批准号: 10672100
• 负责人: TAKAHASHI Koichi
• 金额: $ 2.24万
• 依托单位: Mukogawa Women's University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10672100/
• 关键词: fusogenic liposomes; nasal mucosa; tracheal mucosa; sialidase; trypsin-type endoprotease; リポソーム; センダイウイルス

The objective of the present investigation was to evaluate the usefulness and characterization of fusogenic liposomes (FLs), which have envelope glycoproteins of the Sendai virus on their surface, on a delivery of macromolecules to respiratory mucosa.After nasal administration of FLs and unilaminar liposomes (Lips) containing FITC-dextran (FD) as a model macromolecular compound, FD was not detected in plasma at any times. The recovery of FD after administration of Fls to nose and trachea was significantly lower than that of FD solution or Lips. Time course analysis showed that the rapid fusion to the mucosa in FLs was detectable within 15 min in nose and 30 min in trachea, and reached a maximum value at 30 min in nose and 60 min in trachea. The molecular weights of FD did not affect the binding and fusion of FLs to the mucosa. As evaluated by confocal laser scanning fluorescence microscopy, uptake studies revealed intracellular fluorescence in the epithelial cells. The binding and fusion of FLs to the mucosa were decreased with the coadministration of DTT and pretreatment of sialidase. These results suggested that FLs may recognize sialic acid in the process of the binding and fusion. The binding amount of cationic FLs to nasal mucosa was larger than of anionic FLs, but the fusion amount was almost same between cationic and anionic FLs. Protease inhibitors, such as sialidase inhibitor, typsin inhibitor and chamostat, increased the binding and fusion amount of FLs to the mucosa, but bacitracin did not. From these results, FLs may be useful in localizing macromolecules to nasal mucosa.

本研究的目的是评估表面具有仙台病毒包膜糖蛋白的融合脂质体（FL）在将大分子递送至呼吸道粘膜方面的有用性和表征。经鼻给药FL和含有FITC-葡聚糖（FD）的单层脂质体（Lips）作为模型大分子后 化合物，FD在血浆中任何时候都没有检测到。将Fls注射到鼻子和气管后FD的恢复明显低于FD溶液或唇部。时程分析显示，FLs与粘膜的快速融合在鼻部15分钟和气管部30分钟内即可检测到，并在鼻部30分钟和气管部60分钟时达到最大值。 FD的分子量不影响FL与粘膜的结合和融合。通过共焦激光扫描荧光显微镜评估，摄取研究揭示了上皮细胞中的细胞内荧光。 DTT 和唾液酸酶预处理联合使用可减少 FL 与粘膜的结合和融合。这些结果表明FLs可能在结合和融合过程中识别唾液酸。阳离子FLs与鼻粘膜的结合量大于阴离子FLs，但阳离子FLs与阴离子FLs的融合量几乎相同。蛋白酶抑制剂，如唾液酸酶抑制剂、酪氨酸酶抑制剂和趋化抑制剂，增加了FL与粘膜的结合和融合量，但杆菌肽则没有这种作用。从这些结果来看，FL 可能有助于将大分子定位到鼻粘膜。