| Lung cancer is a kind of cancer with high morbidity and mortality.The treatment of lung cancer is mostly traditional radiotherapy and chemotherapy and surgical resection,these methods often kill the tumor cells,but also damage the normal tissue,causing great harm to the patient's body.Traditional Chinese medicine(TCM)is one of the main methods for the clinical treatment of lung cancer in China.It is proved to be effective in reducing toxicity and increasing the survival and quality of life.The traditional Chinese medicine Rhizoma Curcumae is the dried rhizome of Curcuma,Curcuma of Guangxi and Wen Yujin.It has the function of removing blood and eliminating pain.B-elemene and curcumin are the representatives of volatile oil and curcumin in Curcuma.These two drugs are very important for cancer research.In this paper,the application of ?-elemene and curcumin was used to explore the synergistic effect of two drugs against lung cancer cells.At the same time with the clinical anti-cancer drugs in combination with docetaxel,to explore its inhibition of lung cancer cells.The liposome is composed of phospholipids,which is inserted into the water,and the hydrophobic tail extends into the air,and then forms the spherical vesicles with double lipid molecules.Liposomes can be encapsulated in the bilayer to improve the stability of the drug and reduce the toxicity of the drug.Liposomes in vivo will be macrophage phagocytosis,concentrated in the lungs and other organs,with a targeted,cell affinity and tissue compatibility.Because of the slow release of drug in the target organ or the target tissue,the drug has a slow release property,which can make up the rapid metabolism of ?-elemene and curcumin in vivo.Therefore,the preparation of compound liposomes by ?-elemene and curcumin has reached the target,and it can be used as sustained-release.Aerosol inhalation for the treatment of lung disease has a very good effect,can be directly delivered to the target organ drugs,while avoiding the first pass effect of the liver.There are numerous alveoli in the lung.The alveoli are a kind of semi spherical vesicles formed by a single layer of epithelial cells.There are many capillaries around them.They are very good for the absorption of the drug,but they are also vulnerable to stimulation.Therefore,the safety of nebulized inhalation needs to be guaranteed.In this paper,a preliminary evaluation is made on the stimulation of aerosol inhalation.1.The determination of the optimum proportion of ?-elemene and curcuminFirstly,the methods of human lung cancer cell line A549 and lung adenocarcinoma cell line LLC were established.The principle of MTT method for live cell mitochondrial succinate dehydrogenase in the exogenous MTT reduced to blue violet crystal armour-Formazan and deposited in cells,cells die without this feature.DMSO can dissolve the cells in armour,and by enzyme-linked immunosorbent assay to determine the absorbance value,can reflect the number of living cells.MTT method was used to study the inhibitory effects of different concentrations of ?-elemene and curcumin on the growth of two kinds of cells.The gold formula(q=(EA+B)/(EA+EB-EAxEB))was used to evaluate the synergistic effect of drug combination,the greater the Q value,the more obvious the synergistic effect.Finally,the optimal ratio of concentration of ?-elemene and curcumin was 1:4.When the concentration of ?-elemene was 10 mg·L-1 was,the concentration of curcumin was 40 mg·L-1,and the concentration of docetaxel was 800 mg·L-1 the inhibition rate of LLC cells was 87.44%.2.Preparation and evaluation of compound liposome of ?-elemene and curcuminThe compound liposomes were prepared by the method of the determination of the compatibility ratio.To establish a method for the determination of P-elemene and curcumin in compound liposomes.Design-Expert.8.05b software was used to select the best prescription for curcumin 20 mg,?-elemene 5 mg,lecithin 666.7 mg,cholesterol 133.3 mg,the final use of pH7.0 phosphate buffer salt 10 mL rotary hydration.The results showed that the encapsulation efficiency of ?-elemene was(97.86±1.53)%,and the entrapment efficiency of curcumin was(97.71±1.53)%,and the total drug loading was(0.1925±0.006)%.The appearance of the liposome was yellow,and it was even and no precipitation.The particle size of the liposome was(232.0±6.4)nm,the potential was(0.71±0.1)mV.Through the cell experiment will compound liposomes and solution respectively and combined with docetaxel,the comparison results show that the compound liposomes inhibited the growth of LLC cells was significantly higher than that of solution in high concentration of docetaxel(P<0.05).3.Study on the irritation of liposome inhalationIrritating to the lungs liposome inhalation after atomization inhalation in rats of experimental design,using self-developed atomizing inhalation device(Patent No.:ZL201520442646.5)according to the clinical dosage of atomizing inhalation in rats.In physiological saline were compared,P-elemene and curcumin lipid of rats by stimulation was evaluated by HE staining of lung tissue and bronchoalveolar lavage fluid of BCA of the total protein content and lactate dehydrogenase activity.The results showed that there was no significant difference in the results of the analysis of the pathological sections and the alveolar lavage fluid(P>0.05).So the two drugs liposomes had no significant irritation to the lungs of rats,which laid the foundation for the later research. |
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