Inertial cavitation to non-invasively trigger and monitor intratumoral release of drug from intravenously delivered liposomes

JOURNAL OF CONTROLLED RELEASE

卷:178

Article

Graham, Susan M.¹  Carlisle, Robert¹  Choi, James J.¹  Stevenson, Mark³  Shah, Apurva R.³  Myers, Rachel S.¹  Fisher, Kerry³  Peregrino, Miriam-Bazan²  Seymour, Len³  Coussios, Constantin C.¹ 

[1] Univ Oxford, Inst Biomed Engn, Dept Engn Sci, Oxford OX3 7DQ, England

[2] Inst Invest Biomed Bellvitge, Barcelona 08908, Spain

[3] Univ Oxford, Dept Oncol, Oxford OX3 7DQ, England

关键词: Liposomes;    Ultrasound;    Inertial cavitation;    Drug delivery;    Cancer;   

DOI  :  10.1016/j.jconrel.2013.12.016

来源: Elsevier

【 摘 要 】

The encapsulation of cytotoxic drugs within liposomes enhances pharmacokinetics and allows passive accumulation within tumors. However, liposomes designed to achieve good stability during the delivery phase often have compromised activity at the target site. This problem of inefficient and unpredictable drug release is compounded by the present lack of low-cost, non-invasive methods to measure such release. Here we show that focused ultrasound, used at pressures similar to those applied during diagnostic ultrasound scanning, can be utilised to both trigger and monitor release of payload from liposomes. Notably, drug release was influenced by liposome composition and the presence of SonoVue (R) microbubbles, which provided the nuclei for the initiation of an event known as inertial cavitation. In vitro studies demonstrated that liposomes formulated with a high proportion of 1,2 distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) released up to 30% of payload following ultrasound exposure in the presence of SonoVue (R), provided that the exposure created sufficient inertial cavitation events, as characterised by violent bubble collapse and the generation of broadband acoustic emissions. In contrast a 'Doxil'-like liposome formulation gave no such triggered release. In pre-clinical studies, ultrasound was used as a non-invasive, targeted stimulus to trigger a 16-fold increase in the level of payload release within tumors following intravenous delivery. The inertial cavitation events driving this release could be measured remotely in real-time and were a reliable predictor of drug release. (C) 2013 The Authors. Published by Elsevier B.V.

【 授权许可】

Free