载多柔比星聚乳酸超声靶向给药造影剂的研制与优化。

Development and optimization of a doxorubicin loaded poly(lactic acid) contrast agent for ultrasound directed drug delivery.

机构信息

School of Biomedical Engineering, Science and Health Systems, Drexel University, 3141 Chestnut Street, Philadelphia, PA 19104, USA.

出版信息

J Control Release. 2010 Apr 2;143(1):38-44. doi: 10.1016/j.jconrel.2009.12.021. Epub 2010 Jan 6.

Abstract

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 microg/ml, with a half life of over 15 min. 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.

摘要

提出了一种声敏的静脉内药物输送平台,其中包裹的化疗药物可以到达所需的位置,并且可以在感兴趣的区域使用外部聚焦超声触发药物输送。本文介绍了三种将阿霉素加载到聚乳酸(PLA)壳超声造影剂(UCA)中的方法。通过加载方法和药物浓度比较了对包封效率、体外增强、稳定性、粒径、形态和 UCA 破裂期间释放的影响。含有阿霉素的壳内制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 6.2mg Dox/g PLA,包封效率为 20.5%,表现出光滑的表面形态和紧密的粒径分布(多分散指数=0.309),峰值粒径为 1865nm。在体外,该制剂在 10μg/ml 的剂量下提供 19dB 的增强,半衰期超过 15min。在体内,该制剂在新西兰兔升主动脉中的剂量为 0.15ml/kg 时提供 13.4+/-1.6dB 的超声增强。虽然载药制剂被认为非常适合未来的药物输送实验,但本研究表明,根据药物加载方法的选择,可以针对特定应用定制制剂的性质。

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