Department of Chemistry, Waterloo Institute for Nanotechnology, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada.
Nanoscale Horiz. 2021 Feb 1;6(2):78-94. doi: 10.1039/d0nh00605j. Epub 2021 Jan 5.
Liposomes are a unique platform for drug delivery, and a number of liposomal formulations have already been commercialized. Doxil is a representative example, which uses PEGylated liposomes to load doxorubicin for cancer therapy. Its delivery relies on the enhanced permeability and retention (EPR) effect or passive targeting. Drug loading can be achieved using both standard liposomes and also those containing a solid core such as mesoporous silica and poly(lactide-co-glycolide) (PLGA). Developments have also been made on active targeted delivery using bioaffinity ligands such as small molecules, antibodies, peptides and aptamers. Compared to other types of nanoparticles, the surface of liposomes is fluid, allowing dynamic organization of targeting ligands to achieve optimal binding to cell surface receptors. This review article summarizes development of liposomal targeted drug delivery systems, with an emphasis on the biophysical properties of lipids. In both passive and active targeting, the effects of liposome size, charge, fluidity, rigidity, head-group chemistry and PEGylation are discussed along with recent examples. Most of the examples are focused on targeting tumors or cancer cells. Finally, a few examples of commercialized formulations are described, and some future research opportunities are discussed.
脂质体是一种独特的药物传递平台,已经有许多脂质体制剂实现了商业化。多柔比星脂质体(Doxil)就是一个代表性的例子,它使用聚乙二醇化脂质体来装载多柔比星用于癌症治疗。其传递依赖于增强的通透性和保留(EPR)效应或被动靶向。可以使用标准脂质体和含有固体核心的脂质体(如介孔硅和聚(乳酸-共-乙醇酸)(PLGA))来进行药物装载。使用生物亲和配体(如小分子、抗体、肽和适体)进行主动靶向传递也有了进展。与其他类型的纳米颗粒相比,脂质体的表面是流体的,允许靶向配体的动态组织,以实现与细胞表面受体的最佳结合。本文综述了靶向脂质体药物传递系统的发展,重点介绍了脂质体的物理特性。在被动和主动靶向中,讨论了脂质体大小、电荷、流动性、刚性、头基化学和聚乙二醇化的影响,并结合了最近的一些例子。大多数例子都集中在靶向肿瘤或癌细胞上。最后,描述了一些已商业化的制剂的实例,并讨论了一些未来的研究机会。