可注射的、带状微彩纸屑生物聚合物平台,用于疫苗应用。
Injectable, Ribbon-Like Microconfetti Biopolymer Platform for Vaccine Applications.
机构信息
Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Chapel Hill, North Carolina 27515, United States.
Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, 4211 Marsico Hall, 125 Mason Farm Road, Chapel Hill, North Carolina 27599, United States.
出版信息
ACS Appl Mater Interfaces. 2020 Sep 2;12(35):38950-38961. doi: 10.1021/acsami.0c10276. Epub 2020 Aug 24.
Previously, high-aspect- ratio ribbon-like microconfetti (MC) composed of acetalated dextran (Ace-DEX) have been shown to form a subcutaneous depot for sustained drug release. In this study, MC were explored as an injectable vaccine platform. Production of MC by electrospinning followed by high-shear homogenization allowed for precise control over MC fabrication. Three distinct sizes of MC, small (0.67 × 10.2 μm), medium (1.28 × 20.7 μm), and large (5.67 × 90.2 μm), were fabricated and loaded with the adjuvant, resiquimod. Steady release rates of resiquimod were observed from MC, indicating their ability to create an immunostimulatory depot in vivo. Resiquimod-loaded MC stimulated inflammatory cytokine production in bone marrow-derived dendritic cells without incurring additional cytotoxicity in vitro. Interestingly, even medium and large MC were able to be internalized by antigen-presenting cells and facilitate antigen presentation when ovalbumin was adsorbed onto their surface. After subcutaneous injection in vivo with adsorbed ovalbumin, blank MC of all sizes were found to stimulate a humoral response. Adjuvant activity of resiquimod was enhanced by loading it into MC and small- and medium-sized MC effectively induced a Th1-skewed immune response. Antigen co-delivered with adjuvant-loaded MC of various sizes illustrates a new potential vaccine platform.
先前,高纵横比的带状微珠(MC)由乙酰化葡聚糖(Ace-DEX)组成,已被证明可以形成皮下储库,用于持续释放药物。在这项研究中,MC 被探索作为一种可注射疫苗平台。通过静电纺丝和高剪切匀浆生产 MC 可以精确控制 MC 的制造。制备了三种不同大小的 MC,小(0.67×10.2μm)、中(1.28×20.7μm)和大(5.67×90.2μm),并加载佐剂瑞喹莫德。从 MC 观察到瑞喹莫德的稳定释放率,表明它们有能力在体内创建免疫刺激储库。负载瑞喹莫德的 MC 在体外刺激骨髓来源树突状细胞产生炎症细胞因子,而不会增加额外的细胞毒性。有趣的是,即使是中大和大 MC 也能够被抗原呈递细胞内化,并在其表面吸附卵清蛋白时促进抗原呈递。在体内用吸附的卵清蛋白进行皮下注射后,发现所有大小的空白 MC 都能刺激体液反应。将瑞喹莫德加载到 MC 中增强了其佐剂活性,并且小和中 MC 有效地诱导了 Th1 偏向的免疫反应。各种大小的负载佐剂的 MC 共递送抗原说明了一种新的潜在疫苗平台。
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