Therapeutic efficacy of the combination of doxorubicin-loaded liposomes with inertial cavitation generated by confocal ultrasound in AT2 Dunning rat tumour model

AbstractThe combination of liposomaldoxorubicin (DXR) and confocalultrasound (US) was investigated for the enhancement of drug delivery in a rat tumour model. The liposomes, based on the unsaturated phospholipid dierucoylphosphocholine, were designed to be stable during blood circulation in order to maximize accumulation in tumour tissue and to release drug content upon US stimulation. A confocalUS setup was developed for delivering inertial cavitation to tumours in a well-controlled and reproducible manner. In vitro studies confirm drug release from liposomesas a function of inertial cavitation dose, while in vivo pharmacokinetic studies show long blood circulation times and peak tumour accumulation at 24–48 h post intravenous administration. Animals injected 6 mg kg−1 liposomalDXR exposed to US treatment 48 h after administration show significant tumour growth delaycompared to control groups. A liposomalDXR dose of 3 mg kg−1, however, did not induce any significant therapeutic response. This stud...