Poly(lactide-co-glycolide) microspheres for MRI-monitored transcatheter delivery of sorafenib to liver tumors.
Poly(lactide-co-glycolide) microspheres for MRI-monitored transcatheter delivery of sorafenib to liver tumors.
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DOI：
10.1016/j.jconrel.2014.04.008
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发表时间：
2014-06-28
期刊：
影响因子：
--
通讯作者：
Larson AC
中科院分区：
文献类型：
--
作者：
Chen J;Sheu AY;Li W;Zhang Z;Kim DH;Lewandowski RJ;Omary RA;Shea LD;Larson AC
多激酶抑制剂(MKI)索拉非尼可作为肝细胞癌患者的有效姑息治疗药物。然而，由于口服后常见的全身副作用，患者的耐受性往往很差。局部经导管给药治疗肝脏肿瘤有可能减少全身毒性，同时增加靶向肿瘤的给药剂量。我们开发了索拉非尼洗脱PLG微球，用于在正交异性啮齿动物肝癌模型中通过肝内导管输注给药。这些颗粒还包裹了氧化铁纳米颗粒，允许对肝脏内的生物分布进行磁共振成像(MRI)。载药量为18.6%(w/w)和0.54%(w/w)的≈微球(直径为1μm)在72小时内释放65.2%的索拉非尼。体外研究表明，随着索拉非尼洗脱微球剂量的增加，肝癌细胞的增殖显著降低，估计的IC50为29微克/毫升。在活体研究中，MRI允许在程序中可视化肝脏内的微球递送。在注射微球72小时后，与假对照组肿瘤(35%)和对照组(30%)相比，接受索拉非尼洗脱微球治疗的肿瘤的微血管密度显著减少。这些PLG微球有可能提高分子靶向MKI疗法的疗效，同时通过选择性导管导向给药减少全身暴露。
The multi-kinase inhibitor (MKI) sorafenib can be an effective palliative therapy for patients with hepatocellular carcinoma (HCC). However, patient tolerance is often poor due to common systemic side effects following oral administration. Local transcatheter delivery of sorafenib to liver tumors has the potential to reduce systemic toxicities while increasing the dose delivered to targeted tumors. We developed sorafenib-eluting PLG microspheres for delivery by intra-hepatic transcatheter infusion in an orthotropic rodent HCC model. The particles also encapsulated iron-oxide nanoparticles permitting magnetic resonance imaging (MRI) of intra-hepatic biodistributions. The PLG microspheres (diameter ≈1 μm) were loaded with 18.6% (w/w) sorafenib and 0.54% (w/w) ferrofluid and 65.2% of the sorafenib was released within 72 hours of media exposure. In vitro studies demonstrated significant reductions in HCC cell proliferation with increasing doses of the sorafenib-eluting microspheres, where the estimated IC50 was a 29 ug/mL dose of microspheres. During in vivo studies, MRI permitted intra-procedural visualization of intra-hepatic microsphere delivery. At 72 hours after microsphere infusion, microvessel density was significantly reduced in tumors treated with the sorafenib-eluting microspheres compared to both sham control tumors (by 35%) and controls (by 30%). These PLG microspheres offer the potential to increase the efficacy of molecularly targeted MKI therapies while reducing systemic exposures via selective catheter-directed delivery to HCC.
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影响因子：
158.5
作者：
Llovet, Josep M.;Ricci, Sergio;Bruix, Jordi
通讯作者：
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索拉非尼对亚太地区晚期肝细胞癌患者的疗效和安全性：一项 III 期随机、双盲、安慰剂对照试验
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作者：
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