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凝聚体填充脂质囊泡用于蛋白质递药。

Coacervate-Filled Lipid Vesicles for Protein Delivery.

机构信息

Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Kimball Hall 290, Ithaca, 14853, USA.

出版信息

Macromol Biosci. 2023 Jun;23(6):e2200538. doi: 10.1002/mabi.202200538. Epub 2023 Feb 19.

DOI:10.1002/mabi.202200538
PMID:36749955
Abstract

Macromolecularly crowded coacervate is useful in protein delivery for tissue engineering and regenerative medicine. However, coacervate tends to aggregate easily, which impedes their application. Here, this work presents a method to prepare coacervate with enhanced stability. This work assembles phospholipids on the surface of a coacervate to form lipocoacervate (LipCo). The resultant LipCo possesses a discrete spherical structure with a coacervate interior and phospholipid outer shell. The size of LipCo does not change over the four-week observation window, whereas coacervate coalesced into one bulk phase within 30 min. This work uses vascular endothelial growth factor-C (VEGF-C) and fibroblast growth factor-2 (FGF-2) as examples to test LipCo's ability to maintain protein bioactivity. The in vitro lymphangiogenesis assay demonstrates that human dermal lymphatic endothelial cells (LECs) formed increased network of cord in VEGF-C and FGF-2 loaded LipCo group compared to free proteins and proteins loaded in coacervate. Overall, LipCo could serve as a protein delivery vehicle with improved colloidal stability.

摘要

凝聚物中的大分子物质在组织工程和再生医学的蛋白质传递中很有用。然而,凝聚物容易聚集,这阻碍了它们的应用。在这项工作中,提出了一种制备稳定性增强的凝聚物的方法。该工作在凝聚物表面组装磷脂以形成脂凝聚物(LipCo)。所得的 LipCo 具有离散的球形结构,内部为凝聚物,外部为磷脂壳。在四周的观察窗口内,LipCo 的大小没有变化,而凝聚物在 30 分钟内聚集成一个整体相。该工作使用血管内皮生长因子-C(VEGF-C)和成纤维细胞生长因子-2(FGF-2)为例来测试 LipCo 维持蛋白质生物活性的能力。体外淋巴管生成试验表明,与游离蛋白和凝聚物中装载的蛋白相比,在负载 VEGF-C 和 FGF-2 的 LipCo 组中人真皮淋巴管内皮细胞(LECs)形成了更多的索状网络。总的来说,LipCo 可以作为一种改善胶体稳定性的蛋白质递送载体。

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