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目的制备聚丙烯酸(PAA)修饰氨基改性介孔二氧化硅(MSNs)载三氧化二砷(ATO)纳米粒(PAA-ATO-MSNs),并考察其理化性质、体外释药特性及大鼠体内药动学行为。方法共沉淀法制备氨基改性MSNs,静电吸附载入ATO,PAA酸碱共轭制备PAA-ATO-MSNs。采用透射电镜、小角粉末衍射仪、氮气吸脱附仪、红外光谱仪、热重分析仪、激光粒度仪等考察其理化性质;高速离心法结合电感耦合等离子发射光谱(ICP)测定其包封率及载药量;选用磷酸盐缓冲液(PBS)(p H 5.0、6.0和7.4)作为释放介质,透析袋法考察其体外释药特性;大鼠尾iv给药后,考察ATO体内药动学行为。结果制备的PAA-ATO-MSNs透射电镜下外观呈圆形或类圆形,平均粒径为(158.60±1.32)nm,Zeta电位为(-28.40±0.34)m V,包封率和载药量分别为(40.95±3.21)%和(11.42±1.75)%。体外释药具有p H值响应性,累积释药量随p H值减小而增大。药动学研究表明,与ATO原料药和ATO-MSNs相比,PAA-ATO-MSNs给药后ATO的t1/2β显著延长,AUC显著增大(P<0.01)。结论 PAA-ATO-MSNs体外释药具有明显的p H值响应性及缓释特性,能明显改善ATO大鼠体内药动学行为,该载体作为ATO肿瘤靶向递药系统具有较好的应用前景。
OBJECTIVE To prepare polyamic acid (PAA) -modified amino-modified mesoporous silica (MSNs) loaded with arsenic trioxide (ATO) nanoparticles (PAA-ATO-MSNs) and study its physical and chemical properties, in vitro release characteristics and pharmacokinetics Academic behavior. Methods Amino-modified MSNs were prepared by coprecipitation method. PAA-ATO-MSNs were loaded by electrostatic adsorption onto ATO and acid-base conjugated PAA. The physico-chemical properties were investigated by transmission electron microscopy, small-angle powder diffractometer, nitrogen adsorption-desorption spectrometer, infrared spectrometer, thermogravimetric analyzer and laser particle size analyzer. The entrapment efficiency was determined by high-speed centrifugation and inductively coupled plasma-atomic emission spectrometry (PBS) (p H 5.0, 6.0 and 7.4) as the release medium, dialysis bag method to investigate its in vitro release characteristics; rat tail iv administration, study ATO pharmacokinetic behavior in vivo . Results The appearance of PAA-ATO-MSNs was round or round under TEM. The mean diameter of PAA-ATO-MSNs was (158.60 ± 1.32) nm and the Zeta potential was (-28.40 ± 0.34) (40.95 ± 3.21)% and (11.42 ± 1.75)%, respectively. In vitro release had p H response, and cumulative release increased with p H decrease. Pharmacokinetic studies showed that compared with the ATO drug substance and ATO-MSNs, the t1 / 2β of ATO after PAA-ATO-MSNs administration was significantly prolonged and the AUC was significantly increased (P <0.01). Conclusion PAA-ATO-MSNs release in vitro has obvious p H value response and sustained release properties, can significantly improve the pharmacokinetic behavior of ATO rats, the carrier has good application prospects as ATO tumor targeting drug delivery system .