Unger E C, McCreery T P, Sweitzer R H, Caldwell V E, Wu Y
ImaRx Pharmaceutical Corp., Tucson, AZ 85719, USA.
Invest Radiol. 1998 Dec;33(12):886-92. doi: 10.1097/00004424-199812000-00007.
Paclitaxel-carrying lipospheres (MRX-552) were developed and evaluated as a new ultrasound contrast agent for chemotherapeutic drug delivery.
Paclitaxel was suspended in soybean oil and added to an aqueous suspension of phospholipids in vials. The headspace of the vials was replaced with perfluorobutane gas; the vials were sealed, and they were agitated at 4200 rpm on a shaking device. The resulting lipospheres containing paclitaxel were studied for concentration, size, acute toxicity in mice, and acoustic activity and drug release with ultrasound. Lipospheres containing sudan black dye were produced to demonstrate the acoustically active liposphere (AAL)-ultrasound release concept.
Acoustically active lipospheres containing paclitaxel had a mean particle count of approximately 1 x 10(9) particles per mL and a mean size of 2.9 microns. Acute toxicity studies in mice showed a 10-fold reduction in toxicity for paclitaxel in AALs compared with free paclitaxel. The AALs reflected ultrasound as a contrast agent. Increasing amounts of ultrasound energy selectively ruptured the AALs and released the paclitaxel.
Acoustically active lipospheres represent a new class of acoustically active drug delivery vehicles. Future studies will assess efficacy of AALs for ultrasound-mediated drug delivery.
研发并评估了携带紫杉醇的脂质球（MRX - 552）作为一种用于化疗药物递送的新型超声造影剂。
将紫杉醇悬浮于大豆油中，加入到小瓶中的磷脂水悬浮液中。用全氟丁烷气体置换小瓶的顶部空间；密封小瓶，并在振荡装置上以4200转/分钟的速度振荡。对所得含紫杉醇的脂质球进行浓度、大小、对小鼠的急性毒性以及超声介导的声学活性和药物释放研究。制备含苏丹黑染料的脂质球以证明声学活性脂质球（AAL） - 超声释放概念。
含紫杉醇的声学活性脂质球平均每毫升颗粒数约为1×10⁹个，平均大小为2.9微米。对小鼠的急性毒性研究表明，与游离紫杉醇相比，AAL中紫杉醇的毒性降低了10倍。AAL作为造影剂可反射超声。增加超声能量可选择性地使AAL破裂并释放紫杉醇。
声学活性脂质球代表了一类新型的声学活性药物递送载体。未来的研究将评估AAL在超声介导药物递送方面的疗效。
