Villalonga-Barber Carolina, Micha-Screttas Maria, Steele Barry R, Georgopoulos Aristidis, Demetzos Costas
Institute of Organic and Pharmaceutical Chemistry, National Hellenic Research Foundation, Vassileos Constantinou 48, 11635 Athens, Greece.
Curr Top Med Chem. 2008;8(14):1294-309. doi: 10.2174/156802608785849012.
Two general aspects which need to be considered for the successful application of dendrimers for biomedical purposes are their availability at an acceptable cost and their suitability as regards their pharmacodynamic and pharmacokinetic properties. These two aspects are covered in this review. In the first part, synthetic strategies for the preparation of dendrimers are outlined and emphasis is given to recent work on methodologies whose aim is the development of more efficient routes to dendrimers in terms of the materials used for their synthesis as well as in terms of the procedures required for their purification. These include procedures involving double-stage and double exponential synthesis, orthogonal coupling strategies, self-assembly and solid-phase approaches, as well as particularly useful synthetic protocols such as those used in "click chemistry". The second part of the review deals with the way in which the size, chemical constitution and physicochemical properties of dendrimers used for drug delivery may affect pharmacodynamic and pharmacokinetic parameters which are important considerations for drug bioavailability. This is illustrated by an overview of examples from recent work involving non-steroidal anti-inflammatory drugs, anticancer drugs and antibacterials.
为了将树枝状大分子成功应用于生物医学领域,需要考虑两个总体方面,即它们能否以可接受的成本获得,以及它们在药效学和药代动力学性质方面的适用性。本综述涵盖了这两个方面。在第一部分中,概述了树枝状大分子的合成策略,并着重介绍了近期在方法学方面的工作,这些方法旨在开发更高效的树枝状大分子合成路线,包括从合成所用材料以及纯化所需程序的角度。这些方法包括涉及双阶段和双指数合成、正交偶联策略、自组装和固相方法的程序,以及特别有用的合成方案,如“点击化学”中使用的那些方案。综述的第二部分讨论了用于药物递送的树枝状大分子的大小、化学组成和物理化学性质可能影响药效学和药代动力学参数的方式,而这些参数是药物生物利用度的重要考虑因素。近期涉及非甾体抗炎药、抗癌药和抗菌药的工作实例概述对此进行了说明。