ABSTRACT
Lung cancer is the leading cause of cancer-related deaths. Traditional chemotherapy causes serious toxicity due to the wide bodily distribution of these drugs. Curcumin is a potential anticancer agent but its low water solubility, poor bioavailability and rapid metabolism significantly limits clinical applications. Here we developed a liposomal curcumin dry powder inhaler (LCD) for inhalation treatment of primary lung cancer. LCDs were obtained from curcumin liposomes after freeze-drying. The LCDs had a mass mean aerodynamic diameter of 5.81 μm and a fine particle fraction of 46.71%, suitable for pulmonary delivery. The uptake of curcumin liposomes by human lung cancer A549 cells was markedly greater and faster than that of free curcumin. The high cytotoxicity on A549 cells and the low cytotoxicity of curcumin liposomes on normal human bronchial BEAS-2B epithelial cells yielded a high selection index partly due to increased cell apoptosis. Curcumin powders, LCDs and gemcitabine were directly sprayed into the lungs of rats with lung cancer through the trachea. LCDs showed higher anticancer effects than the other two medications with regard to pathology and the expression of many cancer-related markers including VEGF, malondialdehyde, TNF-, caspase-3 and BCL-2. LCDs are a promising medication for inhalation treatment of lung cancer with high therapeutic efficiency.
ABSTRACT
@#Objective To study the alteration of surfactant protein A and D(sp-A,SP-D)result-ing from pneumcystis carinil pneumonia(PCP)and investigate its implication in the pathogenesis of PCP.Methods SD rat models of PCP were induced by subcutaneous injection of 25 mg cortisone acetate,normal control and negative control as well as bacterial pneumonia group were set up for comparison.During 8～12weeks.broncboalveolar lavage fluid (BALF) of rats was collected.Total nucleate cells of BALF were counted and differentiated as well as the concentrations of surfactant protein A(SP-A)and surfactant pro-tein D(SP-D)were measured by immunoblotting assay.Results The rats were divided into three im-munosuppressive groups,plus a norrflal control group. Group A: normal control(n=6)consisted of healthy SD rats;group B:negative control(n=6)employed rats with cortisone acetate injection over 8weekz without tung infection;group C:bacterial pneumonia(n=11),rats were injected with cortisone ac-etate over 8 weeks and resulted in bacterial pneumonia without other pathogens isolated;group D(n=14):rats were injected with cortisone acetate during 8～12 weeks and resulted in PCP without other pathogens isolated.During PCP infection,the total cell counts and the percentage of polymorphonuclears (PMNs)in BALF were significantly increased(P<0.01),but were lower than those in the bacterial pneumonia group.The concentration of SP-A of BALF in PCP(45.1 μg/ml 4±22.1 μg/m1)was signifi-cantly increased in comparison with that in negative control group(16.2 μg/ml±9.9 gg/ml,P<0.05)and that in bacterial pneumonia group(6.2 μg/ml±5.6 μg/ml,P<0.001).We also found that the rela-tive content of SP-D was significantly higher in PCP(24 249±4 780 grey values)than that in both nega-tive control(13 384±2 887 grey values,P<0.001)and bacterial pneumonia group(11 989±2 750 grey values,P<0.001).SP-A and SP-D were also higher in moderate to severe group of PCP than those seen in mild group(P<0.01,P<0.001).Conclusion There was obvious increase of SP-A and SP-D in PCP rats,and particularly,the change of which was greater than that in bacterial pneumonia.Therefore,the alteration of SP-A and SP-D may be of implication in the prevention and management of PCP.