ACOUSTICALLY ACTIVE LIPOSPHERES CONTAINING PACLITAXEL - A NEW THERAPEUTIC ULTRASOUND CONTRAST AGENT

RATIONALE AND OBJECTIVES. Paclitaxel-carrying lipospheres (MRX-552) we re developed and evaluated as a new ultrasound contrast agent for chem otherapeutic drug delivery. METHODS. Paclitaxel was suspended in soybe an oil and added to an aqueous suspension of phospholipids in vials. T he headspace of the vials mas replaced with perfluorobutane gas; the v ials were sealed, and they were agitated at 4200 rpm on a shaking devi ce. The resulting lipospheres containing paclitaxel were studied for c oncentration, size, acute toxicity in mice, and acoustic activity and drug release with ultrasound. Lipospheres containing sudan black dye m ere produced to demonstrate the acoustically active liposphere (AAL)-u ltrasound release concept, RESULTS. Acoustically active lipospheres co ntaining 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 stu dies 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 r uptured the AALs and released the paclitaxel, CONCLUSIONS. Acousticall y active lipospheres represent a new class of acoustically active drug delivery vehicles. Future studies will assess efficacy of AALs for ul trasound-mediated drug delivery.