Inhalable oridonin-loaded poly(lactic--glycolic)acid large porous microparticles fortreatment of primary non-small cell lung cancer.
10.1016/j.apsb.2016.09.006
- Author:
Lifei ZHU
1
,
2
,
3
;
Miao LI
4
;
Xiaoyan LIU
4
;
Lina DU
4
;
Yiguang JIN
1
;
Author Information
1. Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China
2. Anhui Medical University, Hefei 230001, China
3. Department of Pharmacy, Yangpu Hospital, Tongji University School of Medicine, Shanghai 200090, China.
4. Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China.
- Publication Type:Journal Article
- 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
- From:
Acta Pharmaceutica Sinica B
2017;7(1):80-90
- CountryChina
- Language:English
-
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--glycolic)acid (PLGA) large porous microparticle (LPMP) fortreatment 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.studies 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 LPMPsairway, 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 fortreatment of lung cancer.
