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    Targeted microbubbles carrying lipid-oil-nanodroplets for ultrasound-triggered delivery of the hydrophobic drug, Combretastatin A4

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    Publication date
    2021-08
    Author
    Charalambous, A.
    Mico, V.
    McVeigh, L.E.
    Marston, G.
    Ingram, N.
    Volpato, M.
    Peyman, S.A.
    McLaughlan, J.R.
    Wierzbicki, Antonia
    Loadman, Paul M.
    Bushby, R.J.
    Markham, A.F.
    Evans, S.D.
    Coletta, P.L.
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    Keyword
    Lipid-Oil-Nanodroplets (LONDs)
    Combretastatin A4
    Microbubbles
    Targeting
    Ultrasound trigger
    Rights
    © 2021 The Authors. Published by Elsevier Inc. under a Creative Commons license (https://creativecommons.org/licenses/by/4.0/).
    Peer-Reviewed
    Yes
    Open Access status
    Gold
    
    Metadata
    Show full item record
    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.
    URI
    http://hdl.handle.net/10454/18516
    Version
    Published version
    Citation
    Charalambous A, Mico V, McVeigh LE (2021) Targeted microbubbles carrying lipid-oil-nanodroplets for ultrasound-triggered delivery of the hydrophobic drug, Combretastatin A4. Nanomedicine: Nanotechnology, Biology, and Medicine. 36: 102401.
    Link to publisher’s version
    https://doi.org/10.1016/j.nano.2021.102401
    Type
    Article
    Collections
    Life Sciences Publications

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