Charalambous, A, Mico, V, McVeigh, LE et al. (11 more authors) (2021) Targeted microbubbles carrying lipid-oil-nanodroplets for ultrasound-triggered delivery of the hydrophobic drug, Combretastatin A4. Nanomedicine: Nanotechnology, Biology and Medicine, 36. 102401. ISSN 1549-9634
Abstract
The hydrophobicity of a drug can be a major challenge in its development and prevents the clinical translation of highly potent anti-cancer agents. We have used a lipid-based nanoemulsion termed Lipid-Oil-Nanodroplets (LONDs) for the encapsulation and in vivo delivery of the poorly bioavailable combretastatin A4 (CA4). Drug delivery with CA4 LONDs was assessed in a xenograft model of colorectal cancer. LC–MS/MS analysis revealed that CA4 LONDs, administered at a drug dose four times lower than drug control, achieved equivalent concentrations of CA4 intratumorally. We then attached CA4 LONDs to microbubbles (MBs) and targeted this construct to VEGFR2. A reduction in tumor perfusion was observed in CA4 LONDs-MBs treated tumors. A combination study with irinotecan demonstrated a greater reduction in tumor growth and perfusion (P = 0.01) compared to irinotecan alone. This study suggests that LONDs, either alone or attached to targeted MBs, have the potential to significantly enhance tumor-specific hydrophobic drug delivery.
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Copyright, Publisher and Additional Information: | © 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). | ||||||
Keywords: | Lipid-Oil-Nanodroplets (LONDs); Combretastatin A4; Microbubbles; Targeting; Ultrasound trigger | ||||||
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Institution: | The University of Leeds | ||||||
Academic Units: | The University of Leeds > Faculty of Engineering & Physical Sciences (Leeds) > School of Electronic & Electrical Engineering (Leeds) > Robotics, Autonomous Systems & Sensing (Leeds) The University of Leeds > Faculty of Engineering & Physical Sciences (Leeds) > School of Physics and Astronomy (Leeds) > Molecular & Nanoscale Physics |
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Depositing User: | Symplectic Publications | ||||||
Date Deposited: | 26 Aug 2021 16:22 | ||||||
Last Modified: | 07 Oct 2021 03:53 | ||||||
Status: | Published | ||||||
Publisher: | Elsevier BV | ||||||
Identification Number: | https://doi.org/10.1016/j.nano.2021.102401 |
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