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解析补体介导的过敏反应的复杂性:治疗策略的新兴进展综述

Unravelling the complexity of CARPA: a review of emerging advancements in therapeutic strategies.

作者信息

Saxena Shubhi, Sharma Subhi, Kumar Gourav, Thakur Shubham

机构信息

Department of Quality Assurance, ISF College of Pharmacy, Moga, Punjab, 142001, India.

Department of Pharmaceutics, ISF College of Pharmacy (An Autonomous College), Moga, Punjab, 142001, India.

出版信息

Arch Dermatol Res. 2025 Feb 19;317(1):439. doi: 10.1007/s00403-025-03971-z.

DOI:10.1007/s00403-025-03971-z
PMID:39971823
Abstract

Hypersensitivity reactions to complement activation-related pseudo-allergy (CARPA) pose a serious concern to patient safety when using nanoparticle-based drug delivery systems (NDDS). Complement activation-related pseudo-allergy is a severe, idiosyncratic hypersensitivity reaction consequent to complement activation and liberation of potent pro-inflammatory molecules. Recent developments have concentrated on identifying, managing, and preventing CARPA to improve the efficacy and safety of NDDS, including early identification biomarkers and highly sensitive diagnostic techniques. The development of biocompatible nanoparticles, surface changes to reduce complement activation, and the use of complement inhibitors are some of the innovative strategies for CARPA reduction that are highlighted. Furthermore, newly developed management procedures, such as premedication schedules, customized dosage plans, and real-time monitoring methods, are also covered. The scope of this review encompasses the new diagnostic methods based on in-vitro assays, ex-vivo models, and highly sensitive imaging techniques for the detection of complement activation and other related pseudo-allergic reactions including liposome encapsulation and PEGylation to enhance biocompatibility and decrease immune stimulation. Special emphasis is paid to the application of high-throughput screening technologies and omics tools that enhance the likelihood and evaluation of CARPA immunogenicity. Integration of these approaches forms a comprehensive approach to improving the understanding and administration of CARPA in clinical settings to increase patient safety during nanoparticle-based treatment. The advanced alignments complement regulatory and clinical concerns and connect experimental paradigms to applications, such integration of knowledge provides a platform for the development of next-generation NDDSs for reducing CARPA and enhancing the efficiency of medication delivery thereby increasing patient compliance. This abstract delineates the methods of diagnosing, preventing, and managing CARPA, with addressing the nanotechnology for the problem.

摘要

在使用基于纳米颗粒的药物递送系统(NDDS)时,补体激活相关的类过敏反应(CARPA)引起的超敏反应对患者安全构成严重威胁。补体激活相关的类过敏反应是补体激活和强效促炎分子释放后导致的严重、特异质性超敏反应。最近的进展集中在识别、管理和预防CARPA,以提高NDDS的疗效和安全性,包括早期识别生物标志物和高灵敏度诊断技术。开发生物相容性纳米颗粒、改变表面以减少补体激活以及使用补体抑制剂是一些突出的减少CARPA的创新策略。此外,还涵盖了新开发的管理程序,如预处理方案、定制剂量计划和实时监测方法。本综述的范围包括基于体外试验、离体模型和高灵敏度成像技术的新诊断方法,用于检测补体激活和其他相关的类过敏反应,包括脂质体包封和聚乙二醇化以增强生物相容性和减少免疫刺激。特别强调高通量筛选技术和组学工具的应用,这些技术提高了CARPA免疫原性的可能性和评估。这些方法的整合形成了一种综合方法,以增进对临床环境中CARPA的理解和管理,从而在基于纳米颗粒的治疗过程中提高患者安全性。先进的整合补充了监管和临床方面的关注,并将实验范式与应用联系起来,这种知识的整合为开发下一代用于减少CARPA和提高药物递送效率从而提高患者依从性的NDDS提供了一个平台。本摘要阐述了诊断、预防和管理CARPA的方法,并涉及解决该问题的纳米技术。

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本文引用的文献

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Pseudo-allergic reactions induced by Chinese medicine injections: a review.中药注射剂引起的类过敏反应:综述
Chin Med. 2023 Nov 13;18(1):149. doi: 10.1186/s13020-023-00855-0.
2
Extracellular vesicles: powerful candidates in nano-drug delivery systems.细胞外囊泡:纳米药物递送系统中的有力候选者。
Drug Deliv Transl Res. 2024 Feb;14(2):295-311. doi: 10.1007/s13346-023-01411-x. Epub 2023 Aug 15.
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Role of anti-polyethylene glycol (PEG) antibodies in the allergic reactions to PEG-containing Covid-19 vaccines: Evidence for immunogenicity of PEG.
抗聚乙二醇(PEG)抗体在含 PEG 的 COVID-19 疫苗过敏反应中的作用:PEG 具有免疫原性的证据。
Vaccine. 2023 Jul 12;41(31):4561-4570. doi: 10.1016/j.vaccine.2023.06.009. Epub 2023 Jun 5.
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Targeting the central nervous system: From synthetic nanoparticles to extracellular vesicles-Focus on Alzheimer's and Parkinson's disease.靶向中枢神经系统:从合成纳米颗粒到细胞外囊泡——聚焦阿尔茨海默病和帕金森病。
Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2023 Sep-Oct;15(5):e1898. doi: 10.1002/wnan.1898. Epub 2023 May 8.
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Hypersensitivity reactions to small molecule drugs.小分子药物过敏反应。
Front Immunol. 2022 Nov 10;13:1016730. doi: 10.3389/fimmu.2022.1016730. eCollection 2022.
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Polyethylene glycol (PEG): The nature, immunogenicity, and role in the hypersensitivity of PEGylated products.聚乙二醇(PEG):性质、免疫原性及在 PEG 化产品过敏反应中的作用。
J Control Release. 2022 Nov;351:215-230. doi: 10.1016/j.jconrel.2022.09.031. Epub 2022 Sep 22.
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Biomedical nanomaterials for immunological applications: ongoing research and clinical trials.用于免疫应用的生物医学纳米材料:正在进行的研究和临床试验。
Nanoscale Adv. 2020 Aug 24;2(11):5046-5089. doi: 10.1039/d0na00478b. eCollection 2020 Nov 11.
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Polymeric particle-based therapies for acute inflammatory diseases.用于急性炎症性疾病的基于聚合物颗粒的疗法。
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