Department of Mechanical Engineering and Materials Science, Institute of Materials Science and Engineering , Washington University in St. Louis , St. Louis , Missouri 63130 , United States.
Department of Radiology, Mallinckrodt Institute of Radiology , Washington University School of Medicine , St. Louis , Missouri 63130 , United States.
ACS Appl Mater Interfaces. 2019 Feb 6;11(5):5499-5508. doi: 10.1021/acsami.8b17809. Epub 2019 Jan 28.
Microcapsules are emerging as promising microsize drug carriers due to their remarkable deformability. Shape plays a dominant role in determining their vascular transportation. Herein, we explored the effect of the shape of the microcapsules on the in vivo biodistribution for rational design of microcapsules to achieve optimized targeting efficiency. Silk fibroin, a biocompatible, biodegradable, and abundant material, was utilized as a building block to construct biconcave discoidal and spherical microcapsules with diameter of 1.8 μm and wall thickness of 20 nm. We have compared the cytocompatibility, cellular uptake, and biodistribution of both microcapsules. Both biconcave and spherical microcapsules exhibited excellent cytocompatibility and internalization into cancer cells. During blood circulation in mice, both microcapsules showed retention in liver and kidney and most underwent renal clearance. However, we observed significantly higher accumulation of biconcave silk microcapsules in lung compared with spherical microcapsules, and the accumulation was found to be stable in lung even after 3 days. The higher concentration of biconcave discoidal microcapsules found in lung arises from pulmonary environment, margination dynamics, and enhanced deformation in bloodstream. Red blood cell (RBC)-mimicking silk microcapsules demonstrated here can potentially serve as a promising platform for delivering drugs for lung diseases.
微胶囊由于其显著的变形能力而成为有前途的微尺寸药物载体。形状在决定其血管运输中起着主导作用。在此，我们探讨了微胶囊形状对体内生物分布的影响，以便合理设计微胶囊以实现优化的靶向效率。丝素蛋白是一种生物相容性、可生物降解和丰富的材料，被用作构建具有 1.8μm 直径和 20nm 壁厚的双凹盘形和球形微胶囊的构建模块。我们比较了这两种微胶囊的细胞相容性、细胞摄取和体内分布。双凹和球形微胶囊均表现出优异的细胞相容性和进入癌细胞的能力。在小鼠体内血液循环过程中，两种微胶囊均在肝脏和肾脏中保留，并大部分通过肾脏清除。然而，与球形微胶囊相比，我们观察到双凹丝微胶囊在肺部的积累明显更高，并且即使在 3 天后，肺部的积累仍然稳定。在肺部发现的双凹盘形微胶囊的浓度更高是由于肺部环境、边缘动力学和血流中增强的变形。这里展示的类似于红细胞 (RBC) 的丝微胶囊有可能成为治疗肺部疾病的药物的有前途的平台。
