title: Inhalable oridonin-loaded poly(lactic-co-glycolic)acid large porous microparticles forin situtreatment of primary non-small cell lung cancer.
abstract: Non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancers. Traditional chemotherapy for this disease leads to serious side effects. Here we prepared an inhalable oridonin-loaded poly(lactic-co-glycolic)acid (PLGA) large porous microparticle (LPMP) forin situtreatment of NSCLC with the emulsion/solvent evaporation/freeze-drying method. The LPMPs were smooth spheres with many internal pores. Despite a geometric diameter of ~10 µm, the aerodynamic diameter of the spheres was only 2.72 µm, leading to highly efficient lung deposition.In vitrostudies showed that most of oridonin was released after 1 h, whereas the alveolar macrophage uptake of LPMPs occurred after 8 h, so that most of oridonin would enter the surroundings without undergoing phagocytosis. Rat primary NSCLC models were built and administered with saline, oridonin powder, gemcitabine, and oridonin-loaded LPMPsviaairway, respectively. The LPMPs showed strong anticancer effects. Oridonin showed strong angiogenesis inhibition and apoptosis. Relevant mechanisms are thought to include oridonin-induced mitochondrial dysfunction accompanied by low mitochondrial membrane potentials, downregulation of BCL-2 expressions, upregulation of expressions of BAX, caspase-3 and caspase-9. The oridonin-loaded PLGA LPMPs showed high anti-NSCLC effects after pulmonary delivery. In conclusion, LPMPs are promising dry powder inhalations forin situtreatment of lung cancer.
authors.affiliation: Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China; Anhui Medical University, Hefei 230001, China; Department of Pharmacy, Yangpu Hospital, Tongji University School of Medicine, Shanghai 200090, China.
authors.forename: Lifei
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Du
authors.affiliation: Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China; Anhui Medical University, Hefei 230001, China.
authors.forename: Yiguang
authors.initials: Y
authors.lastname: Jin
keywords: BSA, bovine serum albumin; DAB, 3,3ʹ-diaminobenzidine; DAPI, 4ʹ,6-diamidino-2-phenylindole; DPI, dry powder inhalation; EGFR, epidermal growth factor receptor; FPF, fine particle fraction; HPLC, high performance liquid chromatography; HRP, horseradish peroxidase; LPMP, large porous microparticle; Large porous microparticle; NSCLC, non-small cell lung cancer; Non-small cell lung cancer; Oridonin; PLGA, poly(lactic-co-glycolic)acid; PVA, polyvinyl alcohol; Poly(lactic-co-glycolic)acid; Pulmonary delivery; SEM, scanning electron microscopy; SLF, simulated lung fluid; TCM, traditional Chinese medicine; XRD, X-ray diffraction; qPCR, quantitative polymerase chain reaction