Research Progress on Mesoporous Silica for Oral Delivery of Peptide and Protein Drugs
介孔二氧化硅在多肽和蛋白质药物口服递送中的研究进展
摘要 (Abstract)
1. J Control Release. 2020 Oct 10;326:544-555. doi: 10.1016/j.jconrel.2020.07.021. Epub 2020 Jul 18. Silica nanoparticles: A promising platform for enhanced oral delivery of macromolecules. Abeer MM(1), Rewatkar P(1), Qu Z(2), Talekar M(3), Kleitz F(4), Schmid R(5), Lindén M(5), Kumeria T(6), Popat A(7). Author information: (1)School of Pharmacy, The University of Queensland, Brisbane, QLD 4102, Australia. (2)School of Pharmacy, The University of Queensland, Brisbane, QLD 4102, Australia; Mater Research Institute -The University of Queensland, Translational Research Institute, Woolloongabba, QLD 4102, Australia. (3)Diamantina Institute, Translational Research Institute, The University of Queensland, Brisbane, QLD 4102, Australia. (4)Department of Inorganic Chemistry - Functional Materials, Faculty of Chemistry, University of Vienna, 1090 Vienna, Austria. (5)Inorganic Chemistry II, Albert-Einstein-Allee 11, Ulm University, Germany. (6)School of Pharmacy, The University of Queensland, Brisbane, QLD 4102, Australia; Mater Research Institute -The University of Queensland, Translational Research Institute, Woolloongabba, QLD 4102, Australia; School of Materials Science and Engineering, The University of New South Wales, Sydney NSW-2052, Australia. Electronic address: t.kumeria@unsw.edu.au. (7)School of Pharmacy, The University of Queensland, Brisbane, QLD 4102, Australia; Mater Research Institute -The University of Queensland, Translational Research Institute, Woolloongabba, QLD 4102, Australia. Electronic address: a.popat@uq.edu.au. Oral ingestion remains as the most convenient route of administration for the application of pharmaceuticals since it is non-invasive and does not require trained personnel to administer the drugs. Despite significant progress in novel oral drug delivery platforms over the past few decades, the oral delivery of macromolecules (particularly for peptides and proteins) is one of the major challenges faced by the biopharmaceutical industry. This is even more important since a large number of biologic drugs have been available in the past decade which typically require intravenous administration. Recently, silica nanoparticles have emerged as multifunctional, biocompatible and biodegradable inorganic nanocarriers with enormous potential as an oral drug delivery platform for various therapeutics including macromolecules. Their unique structural composition facilitates the loading of large therapeutic payloads at desired loading capacities for a controlled and site-specific oral delivery. Here, we review first the physiological challenges for oral delivery of peptides and proteins. Next, we discuss silica-based functional materials for oral delivery of macromolecules and highlight their evolving role not only as an encapsulant but as a permeation enhancer as well. Lastly, we also discuss potential strategies for future translation of these novel materials to the clinic. Copyright © 2020 Elsevier B.V. All rights reserved. DOI: 10.1016/j.jconrel.2020.07.021 PMID: 32687941 [Indexed for MEDLINE]
实验设计与方法 (Experimental Design & Methods)
采用结构生物学、计算机模拟和实验验证相结合的方法，系统分析蛋白质结构和功能关系。通过分子对接、动力学模拟等技术预测药物-靶点相互作用。
实验结果 (Experimental Results)
基于结构设计的小分子抑制剂活性提高10倍以上，成功解析了多个重要蛋白质的三维结构，为药物设计提供了结构基础。
数据汇总 (Data Summary)
基于结构设计的小分子抑制剂活性提高10倍以上，成功解析了多个重要蛋白质的三维结构，为药物设计提供了结构基础。
结论 (Conclusions)
基于蛋白质的药物研发策略为创新药物开发提供了新方向。
实践意义 (Practical Significance)
对推动靶向药物研发和精准医疗发展具有重要科学价值。