Establishment of Evaluation Method for Function of Drug Targeting Systems and Systematization of their Physicochemical Character-Function Relationship

近年来，药物靶向技术在药物递送优化方面引起了人们极大的兴趣。药物载体的应用是实现药物靶向性的最有前途的途径之一。虽然人们在开发载体系统方面做出了很大努力，但大多数方法都是通过试验和错误或仅基于经验来完成的。本研究项目的目的如下。第一，建立目标系统的评价方法。二是系统化药物载体的药动学特征。第三，建立药物靶向的方法学。为了在全身、器官和细胞水平上进行研究，进行了体内分布实验、器官灌注实验和使用培养细胞的体外实验。通过这些实验，我们阐明了大分子和微粒载体的药代动力学特征与其物理化学性质（如尺寸和电荷）之间的关系。在此基础上，我们开发了超氧化物歧化酶（抗氧化酶）和维生素K5（凝血剂）的靶向给药系统。

Recently, drug targeting approaches have attracted great interest for optimization of drug delivery. The use of drug carriers is one of the most promising ways to accomplish the drug targeting. Great efforts have been made to develop carrier systems, however, most approaches are done through trial and error or based on only experiences. The purposes of this tesearch project were as follows. First, to establish the evaluation method for targeting systems. Second, to systematize the pharmacokinetic characteristics of drug carriers. Third, to establish the methodology for drug targeting. In order to study at whole body, organ, and cellular levels, in vivo distribution experiments, organ perfusion experiments, and in vitro experiments using cultured cells were carried out. Through these experiments, we have clarified the relationship between the pharmacokinetic characteristics of macromolecular and microparticulate carriers and their physicochemical properties, such as size and charge. Based on the findings, we have developed some targeting delivery systems of superoxide dismutase (antioxidant enzyme) and vitamin K5 (blood coagulant).