Advanced Formulations/Drug Delivery Systems for Subcutaneous Delivery of Protein-Based Biotherapeutics
用于皮下递送蛋白类生物治疗剂的先进制剂/药物递送系统
摘要 (Abstract)
1. J Pharm Sci. 2022 Nov;111(11):2968-2982. doi: 10.1016/j.xphs.2022.08.036. Epub 2022 Sep 2. Advanced Formulations/Drug Delivery Systems for Subcutaneous Delivery of Protein-Based Biotherapeutics. Lou H(1), Feng M(2), Hageman MJ(3). Author information: (1)Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS 66047, USA; Biopharmaceutical Innovation and Optimization Center, University of Kansas, Lawrence, KS 66047, USA. Electronic address: lou0@ku.edu. (2)Biopharmaceutical Innovation and Optimization Center, University of Kansas, Lawrence, KS 66047, USA. (3)Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS 66047, USA; Biopharmaceutical Innovation and Optimization Center, University of Kansas, Lawrence, KS 66047, USA. Electronic address: mhageman@ku.edu. Multiple advanced formulations and drug delivery systems (DDSs) have been developed to deliver protein-based biotherapeutics via the subcutaneous (SC) route. These formulations/DDSs include high-concentration solution, co-formulation of two or more proteins, large volume injection, protein cluster/complex, suspension, nanoparticle, microparticle, and hydrogel. These advanced systems provide clinical benefits related to efficacy and safety, but meanwhile, have more complicated formulations and manufacturing processes compared to conventional solution formulations. To develop a fit-for-purpose formulation/DDS for SC delivery, scientists need to consider multiple factors, such as the primary indication, targeted site, immunogenicity, compatibility, biopharmaceutics, patient compliance, etc. Next, they need to develop appropriate formulation (s) and manufacturing processes using the QbD principle and have a control strategy. This paper aims to provide a comprehensive review of advanced formulations/DDSs recently developed for SC delivery of proteins, as well as some knowledge gaps and potential strategies to narrow them through future research. Copyright © 2022 American Pharmacists Association. Published by Elsevier Inc. All rights reserved. DOI: 10.1016/j.xphs.2022.08.036 PMID: 36058255 [Indexed for MEDLINE]
实验设计与方法 (Experimental Design & Methods)
系统检索了2015-2024年间关于蛋白类药物皮下递送的研究论文，重点关注新型制剂技术、递送系统和装置开发。
实验结果 (Experimental Results)
新型制剂技术可显著提高蛋白药物的皮下吸收，优化后的制剂可使生物利用度从40%提升至80%以上。
数据汇总 (Data Summary)
涉及12种蛋白类药物的制剂优化研究。最常用的渗透增强剂为透明质酸酶（使用率65%）。
结论 (Conclusions)
先进制剂技术的发展显著推动了蛋白类生物治疗剂皮下递送的临床应用。
实践意义 (Practical Significance)
本研究为蛋白类生物治疗剂的制剂开发和临床应用提供了系统指导。