Abstract

Polyelectrolyte complexes and the derivatives thereof comprise some of the most promising vehicles for the encapsulation and delivery of macromolecular therapeutics. In particular, protein therapeutics, which present a host of special considerations, can often be effectively packaged and delivered using interpolyelectrolyte complexes. While the technologies are still in the developmental phase, there are numerous examples of complexes where control is exerted over spacial and temporal delivery of a model protein cargo or candidate protein therapeutic agent. Here we provide a historical and practical background to promote a deeper understanding of interpolyelectrolyte complexes and the derivative technologies. Additionally, we review the physical principles underlying the association of polyelectrolyte complexes and the application of those principles to novel strategies and technologies driving interpolyelectrolyte complexation. Then, the application of polyelectrolyte complex technology to protein therapeutics is discussed in detail including discussions of several types of protein cargo with a special emphasis on Brain-Derived Neurotrophic Factor. Finally, we focus on the use of stealth polymers in block ionomer complexes, specifically PEG; its benefits, flaws, and possible alternatives. Comprehensive understanding of the field may promote the continued development of derivative technologies for the delivery of particularly intransigent protein therapeutics, much as has been accomplished for small molecule drugs. We also aim to link current advances to the historical developments which inaugurated the field. With consideration to the field, industrial and academic researchers can utilize the discussed technologies and continue to elucidate novel modalities for a myriad of therapeutic and commercial applications.

中文翻译：

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聚电解质间复合物作为多肽药物输送的新兴技术

摘要

聚电解质复合物及其衍生物构成了一些最有前途的大分子治疗包封和递送载体。特别是蛋白质疗法，它提出了许多特殊的考虑因素，通常可以使用聚电解质间复合物进行有效包装和递送。虽然这些技术仍处于发展阶段，但有许多复合物的例子，其中对模型蛋白质货物或候选蛋白质治疗剂的空间和时间递送施加控制。在这里，我们提供了历史和实践背景，以促进对聚电解质间复合物和衍生技术的更深入理解。此外，我们回顾了聚电解质络合物结合的物理原理，以及这些原理在驱动聚电解质间络合的新策略和技术中的应用。然后，详细讨论了聚电解质复合物技术在蛋白质治疗中的应用，包括讨论几种类型的蛋白质货物，特别强调脑源性神经营养因子。最后，我们关注隐形聚合物在嵌段离聚物复合物中的使用，特别是 PEG；它的优点、缺陷和可能的替代方案。对该领域的全面了解可能会促进衍生技术的持续发展，以提供特别顽固的蛋白质疗法，就像小分子药物所取得的成就一样。我们还旨在将当前的进展与开创该领域的历史发展联系起来。考虑到该领域，工业和学术研究人员可以利用所讨论的技术并继续阐明用于无数治疗和商业应用的新模式.