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

1. 纳米颗粒的生物相容性评价：利用Biacore评价脂膜与生物组分之间的相互作用。用PVA-R修饰脂膜表面，降低了相互作用力。用J774细胞和激光共聚焦显微镜观察纳米颗粒（脂质体）的细胞包封情况。在颗粒表面涂覆也会降低颗粒的捕集效率。这些结果有力地说明了用亲水聚合物如pva - r - 2对药物载体颗粒进行表面修饰的有效性。制备了一种新型壳聚糖（CS-R）用于脂质体的表面改性，并对其粘接性能进行了评价。壳聚糖仅能包被带负电荷的脂质体，而CS-R则可包被不带电荷的脂质体。所得的CS-R包被脂质体具有相似的粘接性能。在考察CS-R包被脂质体用于口服多肽药物的有效性时，药物系统给药后的初始阶段药物吸附增强。用Caco2细胞，用壳聚糖包覆颗粒载体，对模型药物的透性进行了测试。通过使用载体系统，提高了药物的透性。利用不同类型的颗粒系统，研究了药物在载体系统中的渗透机理。壳聚糖分子具有打开Caco2细胞膜紧密连接的特殊功能。

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.