浅析纳米载体靶向药物递送系统:误区、壁垒与对策

Initial analysis of nano carrier targeted drug delivery system:misunderstanding,barriers and strategy

纳米载体靶向药物递送系统早已受到各国的广泛关注,虽然这一研究方向的论文发表量呈指数增加,却基本没有成药性.本文基于物理化学和生物学原理分析,通过对不同材料和粒径纳米载体扩散系数的实验研究,探讨分子与纳米粒子在水介质中依数性和扩散能力的差异、纳米载体在体内的寻靶过程,从根本上剖析了纳米载体靶向药物递送系统理论中存在的种种误区,揭示了主动靶向修饰的纳米载体并不能够按照载体设计的初衷提高对肿瘤组织的靶向效率的缺陷.证明EPR效应只适用于药物分子与具有足够扩散能力的纳米载体,并提出依靠环境特异性响应的靶向释药、提高纳米载体扩散能力、利用巨噬细胞固有的吞噬作用捕获NPs实现靶向药物递送以及逐级靶向等更具有可行性的靶向递送新策略.

Nano carrier targeted drug delivery system has been widely concerned by many countries.Although papers published in this field have increased exponentially,no drug has come into the market successfully.Based on physicochemical and biological principles and through diffusion coefficient determination of nano carriers in different materials and particle sizes,this paper studies the different diffusion capacity of molecules and nanoparticles in aqueous media,as well as in vivo targeting process of the nanoparticles.After fundamental analysis of various theoretical misunderstanding for nano carriers targeted drug delivery system,we reveal that active targeting nanoparticles could not improve tumor targeting efficiency as their original designations.Then we draw a conclusion that EPR effect is only applicable for drug molecules and nano carriers with sufficient diffusion capacity,and propose new strategies for more feasible nano carriers targeted delivery,including environment-specific responded targeting drug release,improving the nano carrier diffusion capacity,using macrophage phagocytosis capturing NPs to achieve the target drug delivery,and step-by-step targeting strategy.