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以普罗沙姆188为修饰剂制备了隐形丹参酮IIA固体脂质纳米粒(TA-SSLNs),并对其体外吞噬特性和体内药动学进行了评价。采用溶剂乳化蒸发法制备了纳米粒;对纳米粒的理化性质包括粒径,zeta电位,微观结构和稳定性等进行了表征;通过将TA-SSLNs和普通的丹参酮IIA固体脂质纳米粒(TA-NSLNs)与小鼠腹腔巨噬细胞共孵育来考察两种纳米粒的体外细胞吞噬特性;以丹参酮IIA溶液剂(TA-SOL)为对照,考察了TA-NSLNs和TA-SSLNs在大鼠体内的药动学行为。所制备的纳米粒平均粒径为(91.3±3.4)nm,zeta电位为(-19.7±1.6)mV,载药量为(4.7±0.5)%,包封率为(92.5±2.1)%;吞噬试验结果表明,poloxamer188的修饰可以显著降低TA-SSLNs的吞噬量;体内试验表明,TA-SSLNs,TA-NSLNs和TA-SOL的血药浓度数据均符合二室模型,与TA-SOL相比,TA-SSLNs和TA-NSLNs的AUC分别增加了3.70和1.28倍,它们的MRT分别是5.286,3.051和0.820h。使用poloxamer188可以降低微粒被血浆蛋白调理的作用,从而减少巨噬细胞的吞噬,并改变纳米粒的体内药动学行为,增加AUC,延长其在血液中的循环时间。
Stealth Tanshinone IIA Solid Lipid Nanoparticles (TA-SSLNs) were prepared by using Promethium 188 as a modifier, and their in vitro phagocytosis characteristics and in vivo pharmacokinetics were evaluated. The physical and chemical properties of nanoparticles including particle size, zeta potential, microstructure and stability were characterized by TA-SSLNs and ordinary tanshinone IIA solid lipid nanoparticles (TA -NSLNs) were co-incubated with mouse peritoneal macrophages to investigate the phagocytosis of two kinds of nanoparticles in vitro. TA-NSLNs and TA-SSLNs were tested in rats by using tanshinone IIA solution (TA-SOL) Pharmacokinetic behavior. The average diameter of the prepared nanoparticles was (91.3 ± 3.4) nm, the zeta potential was (-19.7 ± 1.6) mV, the drug loading was (4.7 ± 0.5)% and the entrapment efficiency was (92.5 ± 2.1) The results showed that the poloxamer188 modification could significantly reduce the phagocytosis of TA-SSLNs. In vivo experiments showed that the plasma concentrations of TA-SSLNs, TA-NSLNs and TA-SOL were in accordance with the two compartment model. Compared with TA-SOL, The AUCs of TA-SSLNs and TA-NSLNs increased by 3.70 and 1.28 times, respectively, and their MRTs were 5.286, 3.051 and 0.820 h, respectively. Using poloxamer188 reduces the effects of particles being regulated by plasma proteins, thereby reducing phagocytosis by macrophages and changing the in vivo pharmacokinetic behavior of the nanoparticles, increasing AUC and prolonging circulation time in the blood.