Targeted microbubbles carrying lipid-oil-nanodroplets for ultrasound-triggered delivery of the hydrophobic drug, Combretastatin A4
View/ Open
Loadman_et_al_NNBM_Final.pdf (2.021Mb)
Download
Publication date
2021-08Author
Charalambous, A.Mico, V.
McVeigh, L.E.
Marston, G.
Ingram, N.
Volpato, M.
Peyman, S.A.
McLaughlan, J.R.
Wierzbicki, Antonia
Loadman, Paul
Bushby, R.J.
Markham, A.F.
Evans, S.D.
Coletta, P.L.
Rights
© 2021 The Authors. Published by Elsevier Inc. under a Creative Commons license (https://creativecommons.org/licenses/by/4.0/).Peer-Reviewed
YesOpen Access status
openAccessAccepted for publication
2021-03
Metadata
Show full item recordAbstract
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.Version
Published versionCitation
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 Version of Record
https://doi.org/10.1016/j.nano.2021.102401Type
Articleae974a485f413a2113503eed53cd6c53
https://doi.org/10.1016/j.nano.2021.102401