Wuya College of Innovation, Shenyang Pharmaceutical University, Wenhua Road No. 103, 110016 Shenyang, China.
Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
Adv Drug Deliv Rev. 2021 Jul;174:140-167. doi: 10.1016/j.addr.2021.04.006. Epub 2021 May 1.
The global market of pharmaceutical biologics has expanded significantly during the last few decades. Currently, pharmaceutical biologic products constitute an indispensable part of the modern medicines. Most pharmaceutical biologic products are injections either in the forms of solutions or lyophilized powders because of their low oral bioavailability. There are certain pharmaceutical biologic entities formulated into particulate delivery systems for the administration via non-invasive routes or to achieve prolonged pharmaceutical actions to reduce the frequency of injections. It has been well documented that the design of nano- and microparticles via various particle engineering technologies could render pharmaceutical biologics with certain benefits including improved stability, enhanced intracellular uptake, prolonged pharmacological effect, enhanced bioavailability, reduced side effects, and improved patient compliance. Herein, we review the principles of the particle engineering technologies based on bottom-up approach and present the important formulation and process parameters that influence the critical quality attributes with some mathematical models. Subsequently, various nano- and microparticle engineering technologies used to formulate or process pharmaceutical biologic entities are reviewed. Lastly, an array of commercialized products of pharmaceutical biologics accomplished based on various particle engineering technologies are presented and the challenges in the development of particulate delivery systems for pharmaceutical biologics are discussed.
在过去几十年中，药物生物制剂的全球市场显著扩大。目前，药物生物制品已成为现代药物不可或缺的一部分。由于其口服生物利用度低，大多数药物生物制品为注射剂，有溶液或冻干粉形式。某些药物生物实体被制成颗粒递药系统，用于非侵入性途径给药或实现延长药物作用，以减少注射次数。有充分的文献记载，通过各种微粒工程技术设计纳米和微米颗粒，可以使药物生物制品具有某些益处，包括提高稳定性、增强细胞内摄取、延长药效、提高生物利用度、减少副作用和提高患者顺应性。本文综述了基于自下而上方法的微粒工程技术原理，并介绍了影响关键质量属性的重要制剂和工艺参数及其相关数学模型。随后，综述了用于药物生物实体制剂或加工的各种纳米和微米级微粒工程技术。最后，介绍了基于各种微粒工程技术的一系列已商业化的药物生物制品，并讨论了药物生物制剂颗粒递药系统开发中的挑战。
