Biochemistry Programme, Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.
Department of Biological Sciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, Bangi, Selangor, Malaysia.
Adv Protein Chem Struct Biol. 2021;123:193-218. doi: 10.1016/bs.apcsb.2020.08.003. Epub 2020 Sep 23.
Human serum albumin, the primary transport and reservoir protein in the human circulatory system, interacts with numerous endogenous and exogenous ligands of varying structural characteristics. The mode of binding of drugs to albumin is central to understanding their pharmacokinetic profiles and has a major influence on their in vivo efficacy. Altered drug binding to albumin due to drug-drug interactions or abnormal physiology may result in marked changes in the active drug concentration, thus affecting its pharmacokinetic and pharmacodynamic properties. The propensity of drug-drug interaction to be clinically significant as well as possible exploitation of such interactions for therapeutic purposes is reviewed. Being the major organs of albumin metabolism, any impairment in the liver and kidney functions frequently alter the level of serum albumin, which affects the pharmacokinetic profiles of drugs and may have serious clinical implications. The natural function of serum albumin as a drug carrier is facilitated by its interaction with various cellular receptors. These receptors not only promote the uptake of drugs into cells but are also responsible for the extraordinarily long circulatory half-life of albumin. This property in combination with the presence of multiple ligand binding pockets have led to the emergence of serum albumin as an attractive vehicle for novel drug delivery systems. Here, we provide an overview of various albumin-based drug delivery strategies, classified according to their methods of drug attachment, and highlight their experimental and clinical successes.
人血清白蛋白是人体循环系统中主要的转运和储备蛋白，与许多具有不同结构特征的内源性和外源性配体相互作用。药物与白蛋白结合的模式是理解其药代动力学特征的核心，对其体内疗效有重大影响。由于药物相互作用或异常生理导致白蛋白与药物结合的改变，可能导致活性药物浓度的显著变化，从而影响其药代动力学和药效学特性。本文综述了药物相互作用的临床意义以及可能利用这些相互作用达到治疗目的的情况。肝脏和肾脏是白蛋白代谢的主要器官，其功能的任何损害都会经常改变血清白蛋白的水平，从而影响药物的药代动力学特征，并可能产生严重的临床影响。血清白蛋白作为药物载体的天然功能是通过与各种细胞受体相互作用来实现的。这些受体不仅促进药物进入细胞，而且还负责白蛋白异常长的循环半衰期。这种特性与多个配体结合口袋的存在相结合，导致血清白蛋白作为新型药物递送系统的有吸引力的载体的出现。在这里，我们根据药物连接的方法对各种基于白蛋白的药物递送策略进行了概述，并强调了它们的实验和临床成功。
