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Honokiol (HK) have extensive pharmacological activities, but its poor solubility and instability restricted its clinical application and efficacy exertion. HK nanosuspensions (HK-NSps) were designed in this study in order to solve the problems. HK-NSps were prepared by antisolvent precipitation method, using poly-vinylpyrrolidone (PVP) and bovine serum albumin (BSA) as a combined stabilizer. The particle size was measured using dynamic light scattering method, the morphology was observed by transmission electron microscopy. The size change and drug content of HK-NSps in various physiological media during the storage at ambient temperature was examined to evaluate their storage stability. Dialysis method was used to study their drug release in vitro. MTT assay was used to assess their in vitro cytotoxicity against 4T1 breast cancer cell line. Anti-tumor effect in vivo was also investigated in 4T1 tumor-bearing mice. HK-NSps were prepared with high drug loading content of 48.62%, nearly spherical shape and good storage stability. The average particle size was (83.40 ±1.042) nm, the polydispersity index (PDI) value was 0.223 ±0.011, the zeta potential was (-42.2 ±1.2) mV. HK-NSps showed sustained in vitro drug release and enhanced cytotoxicity in contrast to free HK against 4T1 cells (IC50, 8.36 μg·mL-1 vs 37.58 μg·mL-1, P < 0.05). The in vivo study on 4T1 tumor-bearing mice demonstrated that HK-NSps showed good dose-dependent tumor inhibition rate (TIR). In contrast to 4 mg·kg-1 of PTX injection (TIR, 47.9%), medium and high dose of HK-NSps displayed improved therapeutic efficacy (TIR, 55.67% for 40 mg·kg-1, 67.28% for 60 mg·kg-1, P < 0.05). In contrast, the high dose of HK crude drug (60 mg·kg-1) had TIR of only 54.13% even administrated every day. In conclusion, HK-NSps were prepared with small size, high drug-loading capacity, and good stability. The improved in vitro and in vivo antitumor efficacy demonstrated that HK can be a promising antitumor drug in combination with nanosuspensions technology.
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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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