Disposition of ultrasound sensitive polymeric drug carrier in a rat hepatocellular carcinoma model.
Disposition of ultrasound sensitive polymeric drug carrier in a rat hepatocellular carcinoma model.
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DOI：
10.1016/j.acra.2011.06.013
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发表时间：
2011-11
影响因子：
4.8
通讯作者：
Wheatley, Margaret A.
中科院分区：
文献类型：
--
作者：
Cochran, Michael C.;Eisenbrey, John R.;Soulen, Michael C.;Schultz, Susan M.;Ouma, Richard O.;White, Sarah B.;Furth, Emma E.;Wheatley, Margaret A.
已经开发出一种加载阿霉素的微泡，可以用聚焦超声破坏，产生碎片，或能够通过泄漏的肿瘤血管逃逸的“纳米碎片”，促进间质内的积聚。这项研究利用大鼠肝癌模型来检测这种微泡平台的生物分布和肿瘤递送，并与从头开始的载药聚合物纳米粒和游离阿霉素进行比较。制备了含14-C标记阿霉素的微泡(1.8µm)和217 nm纳米粒子。微泡、纳米颗粒、两者的组合或游离阿霉素在携带肝癌的大鼠体内静脉注射，伴随着肿瘤的照射。分别于治疗后4h、7d和14d测定血浆、脏器和肿瘤组织中阿霉素的浓度。处死后测量肿瘤大小，并用放射自显影和组织学进行评估。微泡处理组的阿霉素血药浓度(0.466±0.068%/ml)显著低于游离阿霉素(3.033±0.612%/ml，P=0.0019)。接受微泡治疗的动物心肌中的药物水平明显低于游离阿霉素(0.168%/g组织对0.320%/g组织，p=0.0088)。微泡治疗的肿瘤的药物水平显著高于游离阿霉素治疗的肿瘤(2.491±0.501%/g比0.373±0.087%/g，p=0.0472)。这些肿瘤的生长明显低于接受游离阿霉素治疗的肿瘤(p=0.0390)。超声触发的阿霉素负载微泡提供了增强的、持续的对肿瘤的药物输送，降低了血浆和心肌的阿霉素水平，并阻止了肿瘤的生长。结果提供了比注射从头合成的纳米颗粒更好的治疗方法。
A doxorubicin-loaded microbubble has been developed that can be destroyed with focused ultrasound resulting in fragments, or “nanoshards” capable of escaping through the leaky tumor vasculature, promoting accumulation within the interstitium. This study utilizes a rat liver cancer model to examine the biodistribution and tumoral delivery of this microbubble platform compared with de novo drug-loaded polymer nanoparticles and free doxorubicin. Microbubbles (1.8µm) and 217nm nanoparticles were prepared containing 14-C labeled doxorubicin. Microbubbles, nanoparticles, a combination of the two, or free doxorubicin were administered intravenously in rats bearing hepatomas, concomitant with tumor insonation. Doxorubicin levels in plasma, organs and tumors were quantified after 4hours, 7 and 14days. Tumors were measured upon sacrifice and evaluated with autoradiography and histology. Animals treated with microbubbles had significantly lower plasma doxorubicin concentrations (0.466±0.068%/ml) compared with free doxorubicin (3.033±0.612%/ml, p=0.0019). Drug levels in the myocardium were significantly lower in animals treated with microbubbles compared to free doxorubicin (0.168%/g tissue vs. 0.320%/g, p=0.0088). Tumors treated with microbubbles showed significantly higher drug levels than tumors treated with free doxorubicin (2.491±0.501 %/g vs. 0.373±0.087 %/g, p=0.0472). These tumors showed significantly less growth than tumors treated with free doxorubicin (p=0.0390). Doxorubicin loaded microbubbles triggered with ultrasound provided enhanced, sustained drug delivery to tumors, reduced plasma and myocardium doxorubicin levels and arresting tumor growth. The results offer superior treatment than injection of de novo synthesized nanoparticles.
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影响因子：
10.8
作者：
Kooiman, Klazina;Bohmer, Marcel R.;van Wamel, Annemieke
通讯作者：
van Wamel, Annemieke
影响因子：
37.8
作者：
Price, RJ;Skyba, DM;Skalak, TC
通讯作者：
Skalak, TC
影响因子：
10.8
作者：
Maeda, H;Wu, J;Hori, K
通讯作者：
Hori, K
DOI：
10.1007/s00259-010-1449-6
发表时间：
2010-08-01
影响因子：
9.1
作者：
Eisenbrey, J. R.;Forsberg, F.
通讯作者：
Forsberg, F.
影响因子：
10.8
作者：
Eisenbrey, J. R.;Burstein, O. Mualem;Kambhampati, R.;Forsberg, F.;Liu, J. -B.;Wheatley, M. A.
通讯作者：
Wheatley, M. A.