Pulmonary fibrosis (PF) is a chronic, progressive and irreversible interstitial lung disease that seriously threatens human life and health. Our previous study demonstrated the unique superiority of traditional Chinese medicine cryptotanshinone (CTS) combined with sustained pulmonary drug delivery for treating PF. In this study, we aimed to enhance the selectivity, targeting efficiency and sustained-release capability based on this delivery system. To this end, we developed and evaluated CTS-loaded modified liposomes-chitosan (CS) microspheres SM(CT-lipo) and liposome-exosome hybrid bionic vesicles-CS microspheres SM(LE). The prepared nano-in-micro particles system integrates the advantages of the carriers and complements each other. SM(CT-lipo) and SM(LE) achieved lung myofibroblast-specific targeting through CREKA peptide binding specifically to fibronectin (FN) and the homing effect of exosomes on parent cells, respectively, facilitating efficient delivery of anti-fibrosis drugs to lung lesions. Furthermore, compared with daily administration of conventional microspheres SM(NC) and positive control drug pirfenidone (PFD), inhaled administration of SM(CT-lipo) and SM(LE) every two days still attained similar efficacy, exhibiting excellent sustained drug release ability. In summary, our findings suggest that the developed SM(CT-lipo) and SM(LE) delivery strategies could achieve more accurate, efficient and safe therapy, providing novel insights into the treatment of chronic PF.

中文翻译：

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可吸入的 FN 结合脂质体或脂质体-外泌体混合仿生囊泡封装微粒用于增强肺纤维化治疗

肺纤维化（PF）是一种慢性、进行性、不可逆的间质性肺疾病，严重威胁人类生命和健康。我们前期的研究证明了中药隐丹参酮（CTS）联合肺部持续给药治疗PF的独特优势。在本研究中，我们旨在提高基于该递送系统的选择性、靶向效率和缓释能力。为此，我们开发并评估了负载CTS的修饰脂质体-壳聚糖（CS）微球SM（CT-lipo）和脂质体-外泌体杂化仿生囊泡-CS微球SM（LE）。所制备的纳米微颗粒体系综合了载体的优点，优势互补。 SM(CT-lipo)和SM(LE)分别通过CREKA肽与纤连蛋白(FN)特异性结合以及外泌体对亲代细胞的归巢效应实现肺肌成纤维细胞特异性靶向，促进抗纤维化药物有效递送至肺部病灶。此外，与每日给药常规微球SM(NC)和阳性对照药物吡非尼酮(PFD)相比，每两天吸入给药SM(CT-lipo)和SM(LE)仍能达到相似的疗效，表现出优异的持续药物释放能力。总之，我们的研究结果表明，开发的 SM(CT-lipo) 和 SM(LE) 递送策略可以实现更准确、高效和安全的治疗，为慢性 PF 的治疗提供新的见解。