活血化瘀中药对介孔硅纳米粒小鼠体内分布的影响

Influence of Chinese Materia Medica with Invigorating Blood Circulation and Eliminating Blood Stasis on Distribution of Mesoporous Silica Nanoparticles in Mice

  • 摘要: 目的 制备适宜的介孔硅纳米粒(MSNs)并考察活血化瘀中药对介孔硅纳米粒小鼠体内分布的影响。方法 通过Stober方法制备MSNs,调节不同摩尔比例的正硅酸乙酯(TEOS)和氢氧化钠(NaOH),测定MSNs的粒径、多分散系数(PDI)和Zeta电位,筛选出适宜的MSNs制备工艺,并对其表面进行氨基修饰得到MSNs-NH2。通过动态光散射(DLS)、傅里叶转换红外线光谱(FT-IR)和透射电子显微镜(TEM)等技术表征其结构和形貌。取ICR小鼠每日分别灌服川芎、丹参和水蛭煎液,以灌服生理盐水作为空白对照,10 d后尾静脉注射Cy7荧光染料标记的MSNs-NH2,进行活体成像。结果 在TEOS与NaOH摩尔比为20时制备的MSNs,经氨基修饰得到MSNs-NH2粒径为136.8 nm,PDI为0.17,Zeta电位为16 mV。荧光标记的MSNs-NH2静注后主要分布于肝脾,3种活血化瘀中药预处理组的荧光强度高于对照组,其中川芎组荧光的达峰时间早于丹参组。静注24 h后,川芎组小鼠的肺中显示有荧光,而其他组肺脏无明显荧光。结论 通过调节TEOS和NaOH的摩尔比可以有效调控MSNs的尺度,得到的MSNs-NH2可作为探针用于研究中药与纳米粒的作用关系;服用活血化瘀中药会影响MSNs-NH2在小鼠体内的分布位置和分布时间。

     

    Abstract: OBJECTIVE To prepare the appropriate mesoporous silica nanoparticles (MSNs) and investigate the influence of Chinese materia medica with properties of invigorating blood circulation and eliminating blood stasis on the distribution of MSNs-NH2 in mice. METHODS MSNs were prepared using Stober method. The particle size, polydispersity index (PDI) and Zeta potential of MSNs were measured with different molar ratios of tetraethyl orthosilicate (TEOS) and sodium hydroxide (NaOH). The preparation procedure was optimized for further amino functionality on the surface of MSNs. The structure and morphology of the obtained MSNs-NH2 were characterized by dynamic light scattering (DLS), fourier transform infrared spectroscopy (FT-IR) and transmission electron microscope (TEM). Mice were orally administrated with Ligusticum chuanxiong Hort, Salvia miltiorrhiza Bge or Hirudenipponica Whitman decoction daily, respectively. Mice orally administrated with normal saline was used as the control group. Ten days later, Cy7-labeled MSNs-NH2 was intravenously injected into mice via the tail vein for in vivo imaging. RESULTS Appropriate MSNs were prepared with the molar ratio of TEOS and NaOH being 20. After the surface of MSNs was functionalized with amino groups, the particle size of the MSNs-NH2 was determined to be 136.8 nm with PDI of 0.17 and the Zeta potential of the MSNs-NH2 was 16 mV. Chinese materia medica with properties of invigorating blood circulation and eliminating blood stasis had effect on the distribution of MSNs-NH2in mice. The fluorescence signals of all experimental groups were mainly located in the liver and spleen, and the fluorescence signals of the group treated with Chinese materia medica that supposed to invigorate blood circulation and eliminate blood stasis were stronger than those of control group. In addition, the fluorescence signals of Ligusticum chuanxiong Hort group hit the peak earlier than that of Salvia miltiorrhiza Bget group. Besides, other organs showed no significant fluorescence except for lung in Ligusticum chuanxiong Hort group at 24 h post injection. CONCLUSION By adjusting the molar ratios of TEOS and NaOH, the size of MSNs could be effectively controlled. MSNs-NH2 could be used as a probe to study the relationship between traditional Chinese medicine (TCM) and nanoparticles (NPs). Oral administration of Chinese materia medica with invigorating blood circulation and eliminating blood stasis had effect on the distribution location and peak time of MSNs-NH2 in mice.

     

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