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Melatonin (MLT) is an endogenous chemical that has antitumor effects at high doses. However, it shows low oral bioavailability and short in vivo half-life, leading to drug resistance. Here, liposomal melatonin dry powder inhalers (LMD) were prepared, and were used for treatment of primary rat lung cancer by pulmonary delivery. Liposomal melatonin (LM) was prepared by the ethanol injection method to achieve an entrapment efficiency of 98.89%. LMD was obtained by freeze-drying after LM was mixed with mannitol. LMD appeared as spherical particles under a scanning electron microscope. The rehydrated liposomes had a small size of 65.15 nm and the zeta potential of -14.2 mV without change inentrapment efficiency. LMD had an aerodynamic particle size of 6.73 ±0.012 μm and a fine particle fraction (FPF < 8.06 μm) of 22.2%, suitable for pulmonary delivery. When administered with the same dose, LMD showed much higher inhibition on A549 lung cancer cells than MLT and gemcitabine. LMD of a large dose had no effect on the growth of normal lung epithelial cells (BEAS-2B). Rat lung cancer models were established after 45 days by instilling 3-methylcholanthrene (MCA) and N, N-dimethylnitrosamine (DEN) into the rat lungs once (the experiments had been approved by the ethics committee and carried out in accordance with relevant guidelines and regulations). Decreases of tumor nodules and inflammatory cells in the tumor-bearing rat lungs were observed after treatment of MLT, gemcitabine and LMD by pulmonary delivery compared with the models, wherein LMD was most effective. The efficiencies of inhibition of NF-κB p65, increase of Tunel detection (indicating enhancement of apoptosis), and decrease of malondialdehyde corresponded to LMD being most effective. Therefore, given the fact that LMD can deliver the drug into the tumor tissues of lungs, and it presents as a promising pulmonary inhalable regiment for treatment of lung cancer.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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