| 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。 |
| 关键词: 纳米医学 物理药剂学 理化特性 理论研究 |
| DOI：10.16781/j.0258-879x.2017.06.0699 |
| 投稿时间：2017-05-11修订日期：2017-06-02 |
| 基金项目:国家自然科学基金（31470964，81171450） |
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| Proposing“nano-based physical pharmacy” principle for overcoming bottlenecks in development of nanomedicine |
| CHEN Di,LI Wei* |
(International Joint Cancer Institute, Second Military Medical University, Shanghai 200433, China
*Corresponding author) |
| Abstract: |
| Nanomedicine has shown huge potential in the treatment of cancer, which is not only due to the fact that it can overcome the drawbacks of some small molecular drugs such as insolubility, rapid metabolism, and poor targeting, but also realize the multi modality treatment by containing a variety of molecules. Tremendous novel nano systems referring to above mentioned advantages have been reported so far. However, few newly developed nanomedicine can be approved for clinical applications due to poor stability and rapid metabolism, resulting in the limited efficacy and bottlenecking the development of nanomedicine, that is, "excellent performance in vitro-poor performance in vivo". We believe that the fundamental solution in nanomedicine depends on its basic physical and chemical properties, that is the research and innovation of physical pharmacy theoretical methods of nanopreparation. Herein, focusing on the characteristics of tumor microenvironment and targeting the practical clinical problems, we firstly established a series of physical pharmacy related principles for nanomedicine by the physical and chemical methods combined with the macromolecular Flory-Huggins interaction parameters and scaling theory. Furthermore, taking nanomicelles used to deliver hydrophobic chemotherapeutic drugs as an example, we systemically elaborated the relationship of the physicochemical properties including the carrier composition, self-assembly, drug loading and release, and stability with in vitro and in vivo properties, and explored the related mechanism in vivo. |
| Key words: nanomedicine physical pharmacy physicochemical property theoretical study |
