聚乳酸-乙醇酸共聚物装置:用于持续蛋白质递送的生产与应用

Poly(lactic-co-glycolic acid) devices: Production and applications for sustained protein delivery.

作者信息

Lee Parker W, Pokorski Jonathan K

机构信息

Department of Macromolecular Science and Engineering, School of Engineering, Case Western Reserve University, Cleveland, Ohio.

出版信息

Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2018 Sep;10(5):e1516. doi: 10.1002/wnan.1516. Epub 2018 Mar 13.

Abstract

Injectable or implantable poly(lactic-co-glycolic acid) (PLGA) devices for the sustained delivery of proteins have been widely studied and utilized to overcome the necessity of repeated administrations for therapeutic proteins due to poor pharmacokinetic profiles of macromolecular therapies. These devices can come in the form of microparticles, implants, or patches depending on the disease state and route of administration. Furthermore, the release rate can be tuned from weeks to months by controlling the polymer composition, geometry of the device, or introducing additives during device fabrication. Slow-release devices have become a very powerful tool for modern medicine. Production of these devices has initially focused on emulsion-based methods, relying on phase separation to encapsulate proteins within polymeric microparticles. Process parameters and the effect of additives have been thoroughly researched to ensure protein stability during device manufacturing and to control the release profile. Continuous fluidic production methods have also been utilized to create protein-laden PLGA devices through spray drying and electrospray production. Thermal processing of PLGA with solid proteins is an emerging production method that allows for continuous, high-throughput manufacturing of PLGA/protein devices. Overall, polymeric materials for protein delivery remain an emerging field of research for the creation of single administration treatments for a wide variety of disease. This review describes, in detail, methods to make PLGA devices, comparing traditional emulsion-based methods to emerging methods to fabricate protein-laden devices. This article is categorized under: Biology-Inspired Nanomaterials > Protein and Virus-Based Structures Implantable Materials and Surgical Technologies > Nanomaterials and Implants Biology-Inspired Nanomaterials > Peptide-Based Structures.

摘要

用于蛋白质持续递送的可注射或可植入聚乳酸-乙醇酸共聚物(PLGA)装置已得到广泛研究和应用,以克服由于大分子疗法不良的药代动力学特征而导致治疗性蛋白质需要重复给药的问题。根据疾病状态和给药途径,这些装置可以呈微粒、植入物或贴片的形式。此外,通过控制聚合物组成、装置几何形状或在装置制造过程中引入添加剂,可以将释放速率从数周调整到数月。缓释装置已成为现代医学中一种非常强大的工具。这些装置的生产最初集中在基于乳液的方法上,依靠相分离将蛋白质封装在聚合物微粒中。已经对工艺参数和添加剂的作用进行了深入研究,以确保在装置制造过程中蛋白质的稳定性并控制释放曲线。连续流体生产方法也已被用于通过喷雾干燥和电喷雾生产来制造载有蛋白质的PLGA装置。用固体蛋白质对PLGA进行热处理是一种新兴的生产方法,它允许连续、高通量地制造PLGA/蛋白质装置。总体而言,用于蛋白质递送的聚合物材料仍然是一个新兴的研究领域,旨在为多种疾病创造单次给药治疗方法。这篇综述详细描述了制造PLGA装置的方法,将传统的基于乳液的方法与制造载有蛋白质装置的新兴方法进行了比较。本文分类如下:生物启发纳米材料>基于蛋白质和病毒的结构;可植入材料和手术技术>纳米材料和植入物;生物启发纳米材料>基于肽的结构

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