Fluoroamphiphiles for enhancing immune response of subunit vaccine against SARS-CoV-2

IF 4.4 2区 医学 Q1 PHARMACOLOGY & PHARMACY
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Abstract

In recent decades, protein-based therapy has garnered valid attention for treating infectious diseases, genetic disorders, cancer, and other clinical requirements. However, preserving protein-based drugs against degradation and denaturation during processing, storage, and delivery poses a formidable challenge. Herein, we designed a novel fluoroamphiphiles polymer to deliver protein. Two different formulations of nanoparticles, cross-linked (CNP) and micelle (MNP) polymer, were prepared rationally by disulfide cross-linked and thin-film hydration techniques, respectively. The size, zeta potential, and morphology of both formulations were characterized and the delivery efficacy of both in vitro and in vivo was also assessed. The in vitro findings demonstrated that both formulations effectively facilitated protein delivery into various cell lines. Moreover, in vivo experiments revealed that intramuscular administration of the two formulations loaded with a SARS-CoV-2 recombinant receptor-binding domain (RBD) vaccine induced robust antibody responses in mice without adding another adjuvant. These results highlight the potential use of our carrier system as a safe and effective platform for the in vivo delivery of subunit vaccines.

Abstract Image

用于增强 SARS-CoV-2 亚单位疫苗免疫反应的氟膦类化合物。
近几十年来,基于蛋白质的疗法在治疗传染病、遗传疾病、癌症和其他临床需求方面受到了广泛关注。然而,如何防止蛋白质类药物在加工、储存和递送过程中降解和变性是一项艰巨的挑战。在此,我们设计了一种新型氟膦聚合物来递送蛋白质。通过二硫交联技术和薄膜水合技术,分别合理地制备了交联(CNP)和胶束(MNP)聚合物两种不同配方的纳米粒子。对制备的两种制剂进行了粒度、ZETA电位和形态学表征。同时还评估了两种制剂在体外和体内的递送功效。体外实验结果表明,两种制剂都能有效地将蛋白质输送到各种细胞系中。体内实验表明,肌肉注射这两种负载有 SARS-CoV-2 重组受体结合域(RBD)疫苗的制剂可诱导小鼠产生强有力的抗体反应,而无需添加其他佐剂。这些结果证明,它可以作为一种安全有效的载体,在体内输送亚单位疫苗。
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来源期刊
CiteScore
8.80
自引率
4.10%
发文量
211
审稿时长
36 days
期刊介绍: The European Journal of Pharmaceutics and Biopharmaceutics provides a medium for the publication of novel, innovative and hypothesis-driven research from the areas of Pharmaceutics and Biopharmaceutics. Topics covered include for example: Design and development of drug delivery systems for pharmaceuticals and biopharmaceuticals (small molecules, proteins, nucleic acids) Aspects of manufacturing process design Biomedical aspects of drug product design Strategies and formulations for controlled drug transport across biological barriers Physicochemical aspects of drug product development Novel excipients for drug product design Drug delivery and controlled release systems for systemic and local applications Nanomaterials for therapeutic and diagnostic purposes Advanced therapy medicinal products Medical devices supporting a distinct pharmacological effect.
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