Development and optimization of a doxorubicin loaded poly(lactic acid) contrast agent for ultrasound directed drug delivery.
Development and optimization of a doxorubicin loaded poly(lactic acid) contrast agent for ultrasound directed drug delivery.
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DOI：
10.1016/j.jconrel.2009.12.021
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发表时间：
2010-04-02
影响因子：
10.8
通讯作者：
Wheatley, M. A.
中科院分区：
文献类型：
--
作者：
Eisenbrey, J. R.;Burstein, O. Mualem;Kambhampati, R.;Forsberg, F.;Liu, J. -B.;Wheatley, M. A.
提出了一种回声的静脉内药物递送平台，其中封装的化学治疗剂可以行进到期望的位置，并且可以使用感兴趣区域处的外部聚焦超声来触发药物递送。介绍了三种将阿霉素负载到聚乳酸（PLA）壳超声造影剂（UCA）中的方法。比较了载药方法和药物浓度对UCA包封率、体外增溶、稳定性、粒径、形态及破裂过程中释放的影响。在壳内含有多柔比星的药剂被选为未来肝细胞癌研究的理想候选物。该制剂的最大载药量为6.2 mg Dox/g PLA，包封率为20.5%，显示出光滑的表面形态和紧密的粒径分布（多分散指数= 0.309），峰值尺寸为1865 nm。声学上，该试剂在10 µg/ml剂量下提供19 dB的体外增强，半衰期超过15分钟。在体实验中，当剂量为0.15ml/kg时，对新西兰兔升主动脉的超声增强作用为13.4 ± 1.6dB。虽然药物掺入剂被认为非常适合未来的药物递送实验，但这项研究表明，可以根据药物装载方法的选择针对特定应用定制药物性质。
An echogenic, intravenous drug delivery platform is proposed in which an encapsulated chemotherapeutic can travel to a desired location and drug delivery can be triggered using external, focused ultrasound at the area of interest. Three methods of loading poly lactic acid (PLA) shelled ultrasound contrast agents (UCA) with doxorubicin are presented. Effects on encapsulation efficiency, in vitro enhancement, stability, particle size, morphology and release during UCA rupture are compared by loading method and drug concentration. An agent containing doxorubicin within the shell was selected as an ideal candidate for future hepatocellular carcinoma studies. The agent achieved a maximal drug load of 6.2 mg Dox/g PLA with an encapsulation efficiency of 20.5%, showed a smooth surface morphology and tight size distribution (poly dispersity index = 0.309) with a peak size of 1865 nm. Acoustically, the agent provided 19 dB of enhancement in vitro at a dosage of 10 µg/ml, with a half life of over 15 mins. In vivo, the agent provided ultrasound enhancement of 13.4 ± 1.6 dB within the ascending aorta of New Zealand rabbits at a dose of 0.15 ml/kg. While the drug-incorporated agent is thought to be well suited for future drug delivery experiments, this study has shown that agent properties can be tailored for specific applications based on choice of drug loading method.
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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：
50.5
作者：
O'Brien, MER;Wigler, N;Tendler, C
通讯作者：
Tendler, C
影响因子：
3.3
作者：
Unger, EC;Matsunaga, TO;Quigley, R
通讯作者：
Quigley, R
影响因子：
8.4
作者：
Judson, I;Radford, JA;Nielsen, S
通讯作者：
Nielsen, S
影响因子：
4.1
作者：
Goram, AL;Richmond, PL
通讯作者：
Richmond, PL