粘膜屏障在肺部给药系统中仍然是一个重要的障碍，因为气道中的粘膜纤毛清除加速了吸入纳米颗粒（NPs）的去除。在本研究中，我们设计和开发了可吸入的富琼酸F127修饰的丝素纳米颗粒负载槲皮素（标记为QR-SF（PF127）NPs），旨在解决气道粘膜屏障问题，并改善QR的肿瘤治疗效果。SF NPs 上的PF127涂层能够减弱NPs与粘液蛋白质的相互作用，从而促进SF（PF127）NPs 在粘液层中的扩散。QR-SF（PF127）NPs 的颗粒大小约为200nm，带有负电荷表面，并显示出恒定的药物释放性能。荧光漂白恢复（FRAP）实验和经上皮传输测试表明，QR-SF（PF127）NPs 在人工黏液和单层Calu-3细胞模型中表现出优越的穿透黏液能力。值得注意的是，大量的QR-SF（PF127）NPs 均匀分布在小鼠气道断面中，表明纳米颗粒在呼吸道中保持良好。建立了小鼠黑色素瘤肺转移模型，并且QR-SF（PF127）NPs 在体内的治疗效果显著提高。PF127修饰的SF NPs 可能是减弱与粘液蛋白质相互作用并提高肺部给药系统黏液穿透效率的一种有前景的策略。© 2023 沈阳药科大学. Elsevier B.V. 出版.

The mucosal barrier remains a major barrier in the pulmonary drug delivery system, as mucociliary clearance in the airway accelerates the removal of inhaled nanoparticles (NPs). Herein, we designed and developed the inhalable Pluronic F127-modified silk fibroin NPs loading with quercetin (marked as QR-SF (PF127) NPs), aiming to solve the airway mucus barrier and improve the cancer therapeutic effect of QR. The PF127 coating on the SF NPs could attenuate the interaction between NPs and mucin proteins, thus facilitating the diffusion of SF(PF127) NPs in the mucus layer. The QR-SF (PF127) NPs had particle sizes of approximately 200 nm with negatively charged surfaces and showed constant drug release properties. Fluorescence recovery after photobleaching (FRAP) assay and transepithelial transport test showed that QR-SF (PF127) NPs exhibited superior mucus-penetrating ability in artificial mucus and monolayer Calu-3 cell model. Notably, a large amount of QR-SF (PF127) NPs distributed uniformly in the mice airway section, indicating the good retention of NPs in the respiratory tract. The mice melanoma lung metastasis model was established, and the therapeutic effect of QR-SF (PF127) NPs was significantly improved in vivo. PF127-modified SF NPs may be a promising strategy to attenuate the interaction with mucin proteins and enhance mucus penetration efficiency in the pulmonary drug delivery system.© 2023 Shenyang Pharmaceutical University. Published by Elsevier B.V.