载药微球(4)_杨宁介入医学网

三、载药微球药代动力学

微球荷载表阿霉素的药代动力学研究【8】


VX2肿瘤肝动脉灌注载药微球后，表阿霉素最高血浆浓度是治疗后20分钟，随后逐渐下降。（20分钟是这项研究测量第一个点，所以没有前20分钟的曲线）	VX-2肿瘤动物实验模型，分别在1、3、7天宰杀。肿瘤内最高浓度测量在第三天获得。到第七天肿瘤内药物逐渐下降。肿瘤周围肝组织的药物浓度是肿瘤内药物浓度的5.6%~6.2%。在左或右叶非靶肝组织没有测到表阿霉素的浓度。

Highest intratumoral concentrations at 3 days (40.632-50.052nM/g，7 days drop at 23.1372nM/g)

Photomicrographs (all hematoxylin and eosin [H&E] stain)


Multiple eosinophilic QuadraSpheres occluding a vessel (original magnification, ×50). QuadraSpheres were deformed and conformed to the morphology of the vessel lumen and adjacent	In tumor tissue, most of the QuadraSpheres were eosinophilic with occasional clefts; however, a few of the QuadraSpheres were basophilic	QuadraSpheres were deformed and conformed to the vessel lumen and adjacent particles, whereas Embospheres retained their spherical shape

50-100μm Quadrasphere +4mg doxorubicin

Hepatic Arterial Infusion (HAI) with doxorubicin

TACE with doxorubicin/ lipiodol and 100-300μm Embospheres

兔VX2癌模型分为肝动脉灌注组（HAI）、碘油TACE组（TACE）和载药微球组（QuadraSphere）

治疗前和治疗后10, 20, 40, 60, 120, 和 180分，所有三组血浆表阿霉素浓度在10分钟为高峰，回到接近正常基线为60分钟，持续24小时保持在低位。虽然QuadraSphere血浆浓度显著低于肝动脉灌注组(309.9 ng/ml versus 673.4 ng/mL; p = 0.0183)和TACE组，但没有显著性差异。

doxorubicinol (ng/ml) levels at various times after treatment in the three treatment groups. The x-axis is on a logarithmic scale to accommodate the 1440 hours time point.

he mean intratumoral doxorubicin concentrations in the QuadraSphere group was significantly higher than the other 2 groups, where as the differences between the TACE and HAI groups were not statistically significant.

药物荷载方法和微球大小不同时表阿霉素荷载微球的洗脱特征【12】

两种方法

第一种方法：载药微球被10ml盐水稀释后10分钟+被10ml盐水稀释50mg 表阿霉素孵化2小时
第二种方法：载药微球被25mg表阿霉素稀释后10分钟，再加入10ml盐水稀释25mg 孵化2小时【12】


HepaSphere 30-60μm: At 15 minutes loading was faster with the 2 –step technique	Better elution with 2-step technique

Better elution with 2-step technique【12】	HepaSphere 50-100μm：No considerable differences