高渗透长滞留效应理论在肿瘤靶向药物传递系统设计中的应用进展

Application progress of enhanced permeability and retention effect in tumor targeted macromolecular drug delivery

目的综述高渗透长滞留效应(enhanced permeability and retention effect,简称EPR效应)的发现历史、影响因素及其在大分子药物肿瘤传递中的广泛应用。方法查阅近年来国内外相关文献50篇,对其进行归纳、总结和分析。结果大分子理化性质、肿瘤血管结构及血管调节因子对EPR效应有重要影响,临床上使用硝酸甘油、血管紧张肽转化酶抑制剂等外源性物质来提升EPR效应,以加强微粒给药系统的肿瘤靶向效果。结论 EPR效应作为大分子抗癌药物设计的"金标准",为肿瘤靶向药物传递系统设计的研究与开发提供了重要参考。

Objective To review EPR（ enhanced permeability and retention）effect and its history, factors in- volved and its widespread use in macromolecular drug delivery to tumor. Methods The relevant 50 papers on EPR effect were summarized and analyzed. Results The EPR effect was deeply influenced by the physico- chemical properties of macromolecules, the architecture of tumor vasculature and vascular mediators. Nitro- glycerin, angiotensin-converting enzyme（ACE） inhibitors and other exogenous agents led to a significantly increased on the EPR effect, and hence to strengthen particle drug delivery system tumor targeting effect. Conclusions The EPR effect has become the as＂ gold standard＂ in anticancer drug design using macromolec- ular agents, which will provide important reference in the study of tumor targeting drug delivery system.