Principles of nanoparticle design for overcoming biological barriers to drug delivery.
Principles of nanoparticle design for overcoming biological barriers to drug delivery.
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DOI：
10.1038/nbt.3330
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发表时间：
2015-09
影响因子：
46.9
通讯作者：
Ferrari M
中科院分区：
文献类型：
--
作者：
Blanco E;Shen H;Ferrari M
药物转运的生物屏障阻止了纳米治疗药物在患病部位的成功积累，限制了从癌症到炎症的疾病过程中的有效反应。虽然大量的研究工作旨在将多个功能和部分纳入整个纳米颗粒设计中，但这些策略中的许多策略未能充分解决这些障碍。诸如非特异性分布和治疗药物积累不足等障碍仍然是药物开发人员面临的巨大挑战。需要重新构想传统纳米颗粒才能成功克服这些药物输送障碍。治疗剂的位点特异性递送将仍然是遥远的现实，除非纳米载体设计考虑到颗粒在静脉内施用时遇到的大多数（如果不是全部的话）生物屏障。通过连续解决这些障碍中的每一个，创新的设计特征可以合理地结合起来，这将创造新一代的纳米治疗，实现基于纳米颗粒的药物递送的范式转变。
Biological barriers to drug transport prevent successful accumulation of nanotherapeutics specifically at diseased sites, limiting efficacious responses in disease processes ranging from cancer to inflammation. Although substantial research efforts have aimed to incorporate multiple functionalities and moieties within the overall nanoparticle design, many of these strategies fail to adequately address these barriers. Obstacles, such as nonspecific distribution and inadequate accumulation of therapeutics, remain formidable challenges to drug developers. A reimagining of conventional nanoparticles is needed to successfully negotiate these impediments to drug delivery. Site-specific delivery of therapeutics will remain a distant reality unless nanocarrier design takes into account the majority, if not all, of the biological barriers that a particle encounters upon intravenous administration. By successively addressing each of these barriers, innovative design features can be rationally incorporated that will create a new generation of nanotherapeutics, realizing a paradigmatic shift in nanoparticle-based drug delivery.