Division of Molecular Pharmaceutics and Drug Delivery, College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA; Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt.
The Laboratory of Immunology, Department of Medicine and Moores Cancer Center, University of California San Diego, La Jolla, CA, 92093, USA; FutuRNA Pharmaceuticals, Inc., La Jolla, CA 92037, USA.
Int J Pharm. 2024 Feb 15;651:123757. doi: 10.1016/j.ijpharm.2023.123757. Epub 2023 Dec 30.
Extracellular vesicles (EVs) are endogenous vesicles that comprise a variety of submicron vesicular structures. Among these, exosomes have been widely investigated as delivery systems for small and large molecules. Herein, the thin-film freeze-drying technology was utilized to engineer aerosolizable dry powders of miR-335-laden induced EVs (iEV-335) generated in B cells for potential delivery into the lung to treat primary lung cancer and/or pulmonary metastases. The size distribution, structure, and morphology of iEV-335 were preserved after they were subjected to thin-film freeze-drying with the proper excipients. Importantly, iEV-335, in liquid or reconstituted from thin-film freeze-dried powders, were equally effective in downregulating SOX4 gene expression in LM2 human triple-negative mammary cancer cells. The iEV-335 dry powder compositions showed mass median aerodynamic diameters (MMAD) of around 1.2 µm with > 60 % of the emitted doses had an MMAD of ≤ 3 µm, indicating that the powders can potentially achieve efficient deposition within the alveolar region following oral inhalation, which is desirable for treatment of primary lung cancer and pulmonary metastases. Overall, it is concluded that it is feasible to apply thin-film freeze-drying to prepare aerosolizable dry powders of iEVs for pulmonary delivery.
细胞外囊泡 (EVs) 是由多种亚微米囊泡结构组成的内源性囊泡。在这些囊泡中，外泌体已被广泛研究作为小分子和大分子的递药系统。在此，利用薄膜冷冻干燥技术构建了负载 miR-335 的诱导型 B 细胞 EVs (iEV-335) 的可雾化干粉，以期递送至肺部以治疗原发性肺癌和/或肺转移。适当辅料的薄膜冷冻干燥后，iEV-335 的粒径分布、结构和形态得以保留。重要的是，iEV-335 无论是在液体状态还是从薄膜冷冻干燥粉末中复溶，均能有效下调 LM2 人三阴性乳腺癌细胞中 SOX4 基因的表达。iEV-335 干粉制剂的质量中值空气动力学直径 (MMAD) 约为 1.2 µm，超过 60%的发射剂量的 MMAD 小于等于 3 µm，表明这些粉末在口服吸入后，有可能在肺泡区域实现有效的沉积，这对于原发性肺癌和肺转移的治疗是理想的。总的来说，应用薄膜冷冻干燥技术来制备可雾化的 iEVs 干粉用于肺部递药是可行的。
