Poly(lactide-co-glycolide) microspheres for MRI-monitored delivery of sorafenib in a rabbit VX2 model.
Poly(lactide-co-glycolide) microspheres for MRI-monitored delivery of sorafenib in a rabbit VX2 model.
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DOI：
10.1016/j.biomaterials.2015.05.010
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发表时间：
2015-08
期刊：
影响因子：
14
通讯作者：
Larson, Andrew C.
中科院分区：
文献类型：
--
作者：
Chen, Jeane;White, Sarah B.;Harris, Kathleen R.;Li, Weiguo;Yap, Jonathan W. T.;Kim, Dong-Hyun;Lewandowski, Robert J.;Shea, Lonnie D.;Larson, Andrew C.
经导管肝动脉栓塞术和化疗栓塞术是肝细胞癌的标准局部治疗方法。然而，这些都会导致肿瘤缺氧，从而促进肿瘤血管生成。抗血管生成药物索拉非尼被认为可以改善结果；然而，口服给药限制了患者的耐受性。因此，本研究的目的是制备聚丙交酯-乙交酯微球，用于在肝脏导向的栓塞术中将索拉非尼局部输送到肿瘤。将纳米氧化铁(IONP)共包裹起来，用于微球的磁共振成像(MRI)。采用复乳/溶剂挥发法制备了微球，并对微球的大小、索拉非尼和IONP的含量以及磁共振成像性能进行了表征。在兔VX2肝肿瘤模型中，分别在动脉内注射微球前后进行MRI检查。微球的直径为13微米，索拉非尼和IONP的质量分数分别为8.8%和0.89%。索拉非尼和IONP分别有21%和28%的载药在72小时内释放。兔VX2研究表明，索拉非尼微球可使VEGFR-2活性恢复正常，并降低微血管密度。定量磁共振成像使肝脏内微球分布的体内可视化成为可能。这些方法应该避免全身毒性，MRI允许后续确认微球输送到靶向肝肿瘤。
Transcatheter arterial embolization and chemoembolization are standard locoregional therapies for hepatocellular carcinoma (HCC). However, these can result in tumor hypoxia, thus promoting tumor angiogenesis. The anti-angiogenic agent sorafenib is hypothesized to improve outcomes; however, oral administration limits patient tolerance. Therefore, the purpose of this study was to fabricate poly(lactide-co-glycolide) microspheres for local sorafenib delivery to tumors during liver-directed embolotherapies. Iron oxide nanoparticles (IONP) were co-encapsulated for magnetic resonance imaging (MRI) of microsphere delivery. Microspheres were fabricated using a double emulsion/solvent evaporation method and characterized for size, sorafenib and IONP content, and MRI properties. MRI was performed before and after intra-arterial microsphere infusions in a rabbit VX2 liver tumor model. The microspheres were 13 microns in diameter with 8.8% and 0.89% (w/w) sorafenib and IONP, respectively. 21% and 28% of the loaded sorafenib and IONP, respectively, released within 72 hours. Rabbit VX2 studies demonstrated that sorafenib microspheres normalized VEGFR 2 activity and decreased microvessel density. Quantitative MRI enabled in vivo visualization of intra-hepatic microsphere distributions. These methods should avoid systemic toxicities, with MRI permitting follow-up confirmation of microsphere delivery to the targeted liver tumors.
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影响因子：
2.6
作者：
Lencioni R;Kudo M;Ye SL;Bronowicki JP;Chen XP;Dagher L;Furuse J;Geschwind JF;de Guevara LL;Papandreou C;Takayama T;Yoon SK;Nakajima K;Lehr R;Heldner S;Sanyal AJ
通讯作者：
Sanyal AJ
DOI：
10.1038/nrclinonc.2011.30
发表时间：
2011-05
期刊：
Nature reviews. Clinical oncology
影响因子：
--
作者：
通讯作者：
--
影响因子：
3.6
作者：
Wu, XS;Wang, N
通讯作者：
Wang, N
影响因子：
158.5
作者：
Llovet, Josep M.;Ricci, Sergio;Bruix, Jordi
通讯作者：
Bruix, Jordi
DOI：
10.1080/09205063.2014.982242
发表时间：
2015-01-22
影响因子：
3.6
作者：
Wang, Yujing;Benzina, Abderazak;Koole, Leo H.
通讯作者：
Koole, Leo H.