建立“纳米物理药剂学”原理解决纳米医药发展中的瓶颈问题

发布时间：2018-03-10 07:30

  本文选题：纳米医学　切入点：物理药剂学　出处：《第二军医大学学报》2017年06期 　论文类型：期刊论文

【摘要】：纳米医药在肿瘤治疗方面显示出巨大的潜力,它不仅能克服一些小分子药物水溶性差、代谢快、靶向性差的缺点,还能包载多种分子进行多模态诊疗。尽管优点众多,也有不少新型纳米体系被不断报道,但真正能转化进入临床应用的很少,纳米药物仍存在着体内稳定性差、循环代谢快等问题,从而限制了纳米药物的功效,导致纳米医药进入"体外性能优异-体内表现差"发展瓶颈期。我们认为,从根本上解决纳米医药发展瓶颈问题依赖于其基本的物理化学特性,也就是纳米制剂的物理药剂学理论方法的研究和创新。因此,本文从肿瘤微环境特点出发,围绕临床应用中的实际问题,结合大分子弗洛里赫金斯参数和标度理论等相关理论,以物理化学为手段,建立系列纳米医药的物理药剂学相关原理,并以递送疏水化疗药物的纳米胶束为例,系统地阐述载体组成、自组装、药物装载和释放以及稳定性等相关理化特性与体内外性能的相关关系及体内相互作用的基本机制。
[Abstract]:Nanopharmaceuticals show great potential in tumor therapy, not only to overcome the shortcomings of some small molecular drugs, such as poor water solubility, fast metabolism, poor targeting, but also to carry a variety of molecules for multimodal diagnosis and treatment. Many new nanosystems have been reported, but few of them can really be transformed into clinical applications. Nanopharmaceuticals still have some problems such as poor internal stability, fast circulation and metabolism, which limits the efficacy of nanopharmaceuticals. As a result, nanopharmaceuticals have entered the bottleneck period of "excellent performance in vitro-poor performance in vivo". We believe that the fundamental solution to the bottleneck problem in the development of nanopharmaceuticals depends on their basic physical and chemical properties. That is, the research and innovation of the physical pharmacology theory of nanopharmaceuticals. Therefore, based on the characteristics of tumor microenvironment and the practical problems in clinical application, this paper combines the related theories such as macromolecular Floriheggins parameter and scaling theory. The physical pharmacological principles of a series of nanopharmaceuticals were established by means of physical chemistry. Taking the nano-micelles delivering hydrophobic chemotherapeutic drugs as an example, the composition and self-assembly of the carriers were systematically described. The relationship between the physical and chemical properties of drug loading, release and stability and the relationship between in vivo and in vitro properties, and the basic mechanism of in vivo interaction.
【作者单位】： 第二军医大学国际合作肿瘤研究所;
【基金】：国家自然科学基金(31470964,81171450)~~
【分类号】：R943
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本文编号：1592342