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OBJECTIVE To establish a nano sustained release drug delivery system polysuccinimide(PSI) and hydroxyapatite(HAP) with a hard core-soft coating structure and study the delivery of anti-tumor drug regorafenib. METHODS HAP and PSI were synthesize in the article. The optimal formulation and preparation process of the regorafenib-PSI-HAP was determined by single factor analysis and the box-behnken design(BBD) response surface method. The encapsulation efficiency, drug loading captivity, drug release in vitro, particle size and distribution, Zeta potential and SEM images of regorafenib-PSI-HAP were examined. RESULTS The UV spectrophotometry results showed that the maximum absorption wave of the regorafenib was at 264 nm, the stand curve was A=94.461ρ+0.0304, r2=0.999 8. Meanwhile, between the 2-20 μg·mL-1 of the regorafenib solutions possessed a good linear relationship at this wave. The optimal formulation prepared using MEM detected by BBD was that the concentration of regorafenib was 7.28 mg·mL-1, the mass ratio of HAP to regorafenib was 0.63, and the mass ratio of PSI to HAP was 3.93. The in vitro drug release test showed that PSI-HAP exhibited pH-sensitive drug release, the regorafenib-PSI-HAP can be released totally above pH 7 solution. The PSD was around 300 nm, and Zeta potential was between -10 and -17 mV which was similar to the human cell membrane. CONCLUSION The proposed drug delivery system can be integrated into non-agglomerated spherical nanoparticles of uniform size through a facile preparation process. The particles are easy to sterilize, and large-scale production may be achieved easily. The drug release of PSI-HAP is pH sensitive and stable. Both PSI and nano HAP possess the effect of anti-tumor cell proliferation which is very suitable for the delivery of anti-tumor drugs such as regorafenib in vivo.
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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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