Ultrasound-mediated delivery enhances therapeutic efficacy of MMP sensitive liposomes

• DOI: 10.1016/j.jconrel.2020.06.024
• Publication Date: 2020-07-02T01:40:28Z
• Authors: Marieke Olsman; Viktoria Sereti; Kristine Andreassen; Sofie Snipstad; Annemieke van Wamel; Rasmus Eliasen; Sigrid Berg; Andrew J. Urquhart; Thomas L. Andresen; Catharina de Lang...
• Keywords: Biodistribution; Extravasation; Nanocarriers; Targeted drug delivery

To improve therapeutic efficacy of nanocarrier drug delivery systems, it is essential to their uptake and penetration in tumour tissue, enhance cellular ensure efficient release at the site. Here we introduce a targeting system based on ultrasound-mediated enzyme sensitive liposomes. These liposomes are coated with cleavable poly(ethylene glycol) (PEG) which will be cleaved by two members matrix metalloproteinase family (MMP-2 MMP-9). Cleavage PEG coat can increase destabilize liposomal membrane result accelerated release. The main aim work was study effect focused ultrasound microbubbles MMP liposome. performance liposome compared non-MMP version Doxil-like In vitro, cytotoxicity were studied, while vivo accumulation, biodistribution, microdistribution, investigated. For all tested liposomes, microbubble treatment resulted an improved increased extravasation, from blood vessels into extracellular matrix. Surprisingly, depth independent intensity used. Ultrasound-mediated free doxorubicin significant reduction volume 28 days post first median survival. showed better than indicating that cleaving PEG-layer important. However, outcompeted liposome, both without use microbubbles.