Improving paclitaxel pharmacokinetics by using tumor-specific mesoporous silica nanoparticles with intraperitoneal delivery.
Improving paclitaxel pharmacokinetics by using tumor-specific mesoporous silica nanoparticles with intraperitoneal delivery.
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DOI：
10.1016/j.nano.2016.04.013
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发表时间：
2016-10
期刊：
影响因子：
--
通讯作者：
Lu X
中科院分区：
文献类型：
--
作者：
Fu Q;Hargrove D;Lu X
用于腹膜内（i. p.）开发了递送以利用这些纳米载体在腹膜内注射后的肿瘤特异性积累和紫杉醇从MSN的缓慢释放。与游离紫杉醇相比，紫杉醇负载的MSN观察到肿瘤细胞药物摄取增加3.5倍。使用携带腹膜人胰腺癌MIA PaCa-2的异种移植小鼠的体内研究表明，与游离紫杉醇相比，MSN-紫杉醇制剂表现出腹膜腔停留时间增加3.2倍，吸收进入体循环较慢，全身暴露三分之一，但腹膜肿瘤蓄积增加6.5倍。组织分布成像显示，与其他腹膜组织相比，肿瘤组织中荧光MSNs的累积显著更大。总之，腹膜内给予含药MSN可有效降低紫杉醇的全身暴露并增加腹膜肿瘤蓄积。
Mesoporous silica nanoparticles (MSNs) containing paclitaxel for intraperitoneal (i.p.) delivery were developed to exploit the tumor specific accumulation of these nanocarriers after i.p. injection and the slow release of paclitaxel from the MSNs. A 3.5-fold increase in tumor cellular drug uptake was observed for the paclitaxel-loaded MSNs compared with free paclitaxel. An in vivo study using xenograft mice bearing peritoneal human pancreatic carcinoma MIA PaCa-2 demonstrated that the MSN-paclitaxel formulation, compared to free paclitaxel, exhibited a 3.2-fold increase in peritoneal cavity residence time, slower absorption into the systemic circulation with one third systemic exposure, but a 6.5-fold increase in peritoneal tumor accumulation. Tissue distribution imaging showed significantly greater accumulation of fluorescent MSNs in tumor tissues compared to other peritoneal tissues. In conclusion, intraperitoneal administration of drug-containing MSNs was effective at reducing systemic exposure and increasing the peritoneal tumor accumulation of paclitaxel.