Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshidashimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.
Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshidashimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.
J Control Release. 2022 Oct;350:486-493. doi: 10.1016/j.jconrel.2022.05.063. Epub 2022 Aug 31.
The enhanced permeability and retention (EPR) effect has been the gold standard in developing drug delivery systems for passive tumor targeting. Although the importance of this concept remains unchanged, some controversies have arisen. In this review, various strategies for tumor targeting using macromolecules and nanoparticles based on the EPR effect are discussed from the viewpoint of pharmacokinetics. Overall, such strategies seek to retain therapeutic material in the blood circulation, which is a key factor for successful targeting. Strategies using macromolecules, including antibody-drug conjugates, serum albumin-based delivery systems, PEGylated recombinant proteins, and stealth liposomes as well as nanoparticle-based strategies such as those based on lipid nanoparticles, and polymeric micelles, have been discussed. The feasibility of small extracellular vesicles, a new class of nanosized delivery carriers, is also discussed.
增强的通透性和保留（EPR）效应一直是开发用于被动肿瘤靶向的药物递送系统的金标准。尽管这一概念的重要性仍然没有改变，但也出现了一些争议。在这篇综述中，从药代动力学的角度讨论了基于 EPR 效应的用于肿瘤靶向的各种大分子和纳米颗粒的策略。总的来说，这些策略旨在使治疗材料保留在血液循环中，这是成功靶向的关键因素。讨论了使用大分子的策略，包括抗体药物偶联物、基于血清白蛋白的递药系统、聚乙二醇化重组蛋白和隐形脂质体，以及基于纳米颗粒的策略，如基于脂质纳米粒和聚合物胶束的策略。还讨论了小细胞外囊泡这一类新型纳米递药载体的可行性。
