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治疗药物递送系统的合理设计与工程:胶体与表面科学中的生物医学实践

Rational design and engineering of delivery systems for therapeutics: biomedical exercises in colloid and surface science.

作者信息

Kostarelos Kostas

机构信息

Imperial College Genetic Therapies Centre, Flowers Building, South Kensington Campus, Imperial College London, London SW7 2AZ, UK.

出版信息

Adv Colloid Interface Sci. 2003 Dec 1;106:147-68. doi: 10.1016/s0001-8686(03)00109-x.

Abstract

Engineering delivery systems of therapeutic agents has grown into an independent field, transcending the scope of traditional disciplines and capturing the interest of both academic and industrial research. At the same time, the acceleration in the discovery of new therapeutic moieties (chemical, biological, genetic and radiological) has led to an increasing demand for delivery systems capable of protecting, transporting, and selectively depositing those therapeutic agents to desired sites. The vast majority of delivery systems physically reside in the colloidal domain, while their surface properties and interfacial interactions with the biological milieu critically determine the pharmacological profiles of the delivered therapeutic agents. Interestingly though, the colloidal and surface properties of delivery systems are commonly overlooked in view of the predominant attention placed on the therapeutic effectiveness achieved. Moreover, the development and evaluation of novel delivery systems towards clinical use is often progressed by serendipity rather than a systematic design process, often leading to failure. The present article will attempt to illustrate the colloid and interfacial perspective of a delivery event, as well as exemplify the vast opportunities offered by treating, analysing and manipulating delivery systems as colloidal systems. Exploring and defining the colloid and surface nature of the interactions taking place between the biological moieties in the body and an administered delivery vehicle will allow for the rational engineering of effective delivery systems. A design scheme is also proposed on the way in which the engineering of advanced delivery systems should be practiced towards their transformation from laboratory inventions to clinically viable therapeutics. Lastly, three case studies are presented, demonstrating how rational manipulation of the colloidal and surface properties of delivery systems can lead to newly engineered systems relevant to chemotherapy, gene therapy and radiotherapy.

摘要

治疗剂递送系统已发展成为一个独立的领域,超越了传统学科的范畴,并引起了学术研究和工业研究的兴趣。与此同时,新治疗部分(化学、生物、基因和放射学)发现速度的加快,导致对能够保护、运输并将这些治疗剂选择性地沉积到所需部位的递送系统的需求不断增加。绝大多数递送系统实际上处于胶体领域,而它们的表面性质以及与生物环境的界面相互作用,关键地决定了所递送治疗剂的药理学特征。然而有趣的是,鉴于主要关注所实现的治疗效果,递送系统的胶体和表面性质通常被忽视。此外,新型递送系统向临床应用的开发和评估往往是偶然进行的,而非通过系统的设计过程,这常常导致失败。本文将试图阐述递送过程的胶体和界面观点,并举例说明将递送系统作为胶体系统进行处理、分析和操纵所带来的巨大机遇。探索和界定体内生物部分与给药递送载体之间相互作用的胶体和表面性质,将有助于合理设计有效的递送系统。还提出了一种设计方案,说明应如何开展先进递送系统的工程设计,使其从实验室发明转化为临床上可行的治疗方法。最后,给出了三个案例研究,展示了对递送系统的胶体和表面性质进行合理操纵如何能够产生与化疗、基因治疗和放射治疗相关的新工程系统。

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