Drug therapies for acute lung injury (ALI) are far from satisfactory, primarily because drugs cannot specifically target the lungs. Direct delivery of drugs to the deep alveolar regions by inhalation administration is crucial for the treatment of ALI. However, conventional inhalable carriers such as lactose and mannitol are generally inactive. Therefore, the use of a novel pharmacologically active carrier for pulmonary delivery may produce synergetic effects in treating ALI. Considering the pathophysiological environment of ALI, which typically featured excessive reactive oxygen species (ROS) and acute inflammation, we synthesized a novel kind of biodegradable and ROS-sensitive cross-linked covalent cyclodextrin frameworks (OC-COF) with uniform inhalable particle size to treat ALI. OC-COF was devised to incorporate H 2 O 2 -scavenging peroxalate ester linkages, which could hydrolyze and eliminate ROS generated in inflammatory sites. Ligustrazine (LIG), an antioxidant and anti-inflammatory natural compound, was loaded into OC-COF and evaluated as a dry powder inhaler (LIG@OC-COF) in vitro and in vivo, showing favorable aerodynamic properties and prominent antioxidant and anti-inflammatory capacities for the synergistic effects of OC-COF and LIG. In ALI rats, inhalation of LIG@OC-COF with a one-fifth LIG dose significantly alleviated the inflammation, oxidant stress, and lung damage. Western blot analysis demonstrated that LIG@OC-COF protected the lungs by regulating the Nrf2/NF-κB signaling pathway. In summary, this study provides a novel ROS-responsive material as an inhalable particulate carrier for the improved treatment of ALI and other medical conditions.
Lung cancer is one of the most fatal cancers due to its high metastatic rate. Traditional Chinese medicine has been used in cancer patients for decades to improve quality of life and prolong survival time. The present study used a novel Qiyusanlong (QYSL) decoction composed of 10 kinds of Chinese medicine including astragalus membranaceus (Huangqi), polygonatumod oratum (yuzu), scolopendra (tianlong), pberetima (dilong), solanum nigrum (longkui), herbahedyotis (baihushecao), semen coicis (yiyiren), euphorbia helioscopia (zeqi), curcuma longa (eshu) and tendril-leaved fritillary bulb (chuanbei). The effects and function of the QYSL decoction remain to be elucidated. The present study established a mouse xenograft model using Lewis lung carcinoma cell injection and administered different doses of QYSL decoction to the mice. It was demonstrated that the chemotherapy drug Cisplatin (DDP) and QYSL decoction repressed lung tumor growth, and the inhibitory effect of DDP was more significant. Furthermore, QYSL decoction and DDP modulated the expression of regulatory proteins in the Wnt/β‑catenin pathway, including Wnt1, Wnt2, Wnt5a and glycogen synthase kinase 3β, detected by western blotting, and affected the signals of cluster of differentiation 44 variation 6 and Survivin in tumor tissues, examined via immunohistochemistry. The combination of QYSL decoction and DDP enhanced the inhibitory effect. These data demonstrated that the QYSL decoction repressed lung tumor development via the Wnt/β‑catenin pathway. The therapeutic effect of QYSL decoction alone was milder compared with DDP, however the combination of QYSL decoction and chemotherapy exhibited an increased the rapeutic effect compared with the treatments administered alone. These findings revealed the function of QYSL decoction as a lung cancer treatment and provided insight for a novel lung cancer therapy.
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