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Studies on nano-particulate systems and their bio-response for drug delivery

纳米颗粒系统及其药物递送生物反应的研究

基本信息

批准号：
14370731
负责人：
TAKEUCHI Hirofumi
金额：
$ 7.49万
依托单位：
Gifu Pharmaceutical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

项目摘要

1. Assessment of bio-compatibility of nano-particlesThe interaction between lipid membrane and bio-components were evaluated by use of Biacore. The interactive force was reduced by modifying the surface of lipid membrane with PVA-R. The cell entrapment of nano particles (liposomes) were measured with J774 cells and confocal laser microscopy. The entrapment efficiency was also decreased by coating the surface of particles. These results strongly suggested the usefulness of surface modification of drug carrier particles with hydrophilic polymers such as PVA-R.2. Design of mucoadhesive particles with partly hydrophobic chitosanNew type of chitosan (CS-R) was prepared for surface modification of liposomes and its mucoadhesive properties were evaluated. While chitosan can coat the only negatively charged liposomes, CS-R was found to be applicable for coating of non-charged liposomes. The resultant CS-R coated liposomes possessed similar mucoadhesive properties. In examining the effectiveness of CS-R coated liposomes in oral administration of peptide drugs, drug adsorption was enhanced in the initial stage after administration of the drug systems.3. Membrane transport of drug with the particular systemsThe permeability of model drug was tested with the particle carriers coated with chitosan by use of Caco2 cell. The drug permiability was enhanced by use of the carrier systems. The mechanism of the drug permeation with the carrier systems were examined by use of various types of particulate systems. It was found that chitosan molecules have a special function to open the tight junction of the Caco2 cell membranes.

1.纳米粒生物相容性评价采用Biacore生物相容性分析仪评价纳米粒与脂质膜的相互作用。用PVA-R对脂膜表面进行改性，降低了相互作用力。用J774细胞和激光共聚焦显微镜测定纳米脂质体的细胞包封率。表面包覆也会降低包封率。这些结果强烈表明，用PVA-R等亲水性聚合物对药物载体颗粒进行表面修饰是有用的。2。部分疏水性壳聚糖微球的设计制备了新型壳聚糖（CS-R）用于脂质体的表面修饰，并对其粘附性能进行了评价。虽然壳聚糖可以包覆仅带负电荷的脂质体，但发现CS-R适用于包覆不带电荷的脂质体。所得CS-R包衣脂质体具有相似的粘膜粘附特性。在考察CS-R包衣脂质体口服给药肽类药物的有效性时，药物系统给药后的初始阶段药物吸附增强.药物在特定系统中的膜转运利用Caco 2细胞对模型药物在壳聚糖包裹的微粒载体上的渗透性进行了测试。通过使用载体系统提高了药物渗透性。通过使用各种类型的微粒系统，研究了载体系统的药物渗透机制。结果发现，壳聚糖分子具有打开Caco 2细胞膜紧密连接的特殊功能。