Therapeutic efficacy of the combination of doxorubicin-loaded liposomes with inertial cavitation generated by confocal ultrasound in AT2 Dunning rat tumour model. (September 2014)

• Record Type: Journal Article
• Authors: Mestas, Jean-Louis; Fowler, R. Andrew; Evjen, Tove J.; Somaglino, Lucie; Moussatov, Alexei; Ngo, Jacqueline; Chesnais, Sabrina; Røgnvaldsson, Sibylla; Fossheim, Sigrid L.; Nilssen, Esben A.; Lafon, Cyril
• Is Part Of: Journal of drug targeting. Volume 22:Number 8(2014)
• Page Start: 688
• Page End: 697
• Publication Date: 2014-09
• Subjects: Drug delivery systems -- Periodicals; Drug Delivery Systems; Vehicles; Drug Administration Routes; Drug Evaluation; 615.7
• DOI: 10.3109/1061186X.2014.906604
• Languages: English
• ISSNs: 1061-186X

Abstract

<abstract> <title>Abstract</title> <p>The combination of liposomal doxorubicin (DXR) and confocal ultrasound (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 confocal US setup was developed for delivering inertial cavitation to tumours in a well-controlled and reproducible manner. <italic>In vitro</italic> studies confirm drug release from liposomes as a function of inertial cavitation dose, while <italic>in vivo</italic> pharmacokinetic studies show long blood circulation times and peak tumour accumulation at 24–48 h post intravenous administration. Animals injected 6 mg kg⁻¹ liposomal DXR exposed to US treatment 48 h after administration show significant tumour growth delay compared to control groups. A liposomal DXR dose of 3 mg kg⁻¹, however, did not induce any significant therapeutic response. This study demonstrates that inertial cavitation can be generated in such a fashion as to disrupt drug carrying liposomes which have accumulated in the tumour, and thereby increase therapeutic effect with a minimum direct effect on the tissue. Such an approach is an important step towards a therapeutic application of cavitation-induced drug delivery and reduced chemotherapy toxicity.</p> </abstract>