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药物递送对聚合物的探索:前沿何在?

Drug delivery's quest for polymers: Where are the frontiers?

作者信息

Merkle Hans P

机构信息

Institute of Pharmaceutical Sciences, ETH Zurich, Campus Hönggerberg, Vladimir-Prelog-Weg 1-5/10, CH-8093 Zürich, Switzerland.

出版信息

Eur J Pharm Biopharm. 2015 Nov;97(Pt B):293-303. doi: 10.1016/j.ejpb.2015.04.038.

Abstract

Since the legendary 1964 article of Folkman and Long entitled "The use of silicone rubber as a carrier for prolonged drug therapy" the role of polymers in controlled drug delivery has come a long way. Today it is evident that polymers play a crucial if not the prime role in this field. The latest boost owes to the interest in drug delivery for the purpose of tissue engineering in regenerative medicine. The focus of this commentary is on a selection of general and personal observations that are characteristic for the current state of polymer therapeutics and carriers. It briefly highlights selected examples for the long march of synthetic polymer-drug conjugates from bench to bedside, comments on the ambivalence of selected polymers as inert excipients versus biological response modifiers, and on the yet unsolved dilemma of cationic polymers for the delivery of nucleic acid therapeutics. Further subjects are the complex design of multifunctional polymeric carriers including recent concepts towards functional supramolecular polymers, as well as observations on stimuli-sensitive polymers and the currently ongoing trend towards natural and naturally-derived biopolymers. The final topic is the discovery and early development of a novel type of biodegradable polyesters for parenteral use. Altogether, it is not the basic and applied research in polymer therapeutics and carriers, but the translational process that is the key hurdle to proceed towards an authoritative approval of new polymer therapeutics and carriers.

摘要

自1964年福克曼和朗发表具有传奇色彩的《硅橡胶作为长期药物治疗载体的应用》一文以来,聚合物在控释给药中的作用已经取得了长足的发展。如今,显而易见的是,聚合物在该领域即便不是发挥首要作用,也起着至关重要的作用。最新的推动因素源自再生医学中组织工程对药物递送的关注。本评论的重点是一系列一般性和个人性的观察结果,这些观察结果是聚合物治疗学和载体当前状况的特征。它简要突出了合成聚合物 - 药物偶联物从实验室走向临床应用的漫长历程中的精选实例,评论了某些聚合物作为惰性辅料与生物反应调节剂的矛盾之处,以及阳离子聚合物在递送核酸治疗药物方面尚未解决的困境。其他主题包括多功能聚合物载体的复杂设计,包括功能性超分子聚合物的最新概念,以及对刺激敏感聚合物的观察和目前对天然及天然衍生生物聚合物的发展趋势。最后一个主题是一种新型用于肠胃外给药的可生物降解聚酯的发现和早期开发。总而言之,聚合物治疗学和载体的基础研究与应用研究并非关键障碍,而转化过程才是迈向新型聚合物治疗学和载体获得权威批准的关键障碍。

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