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

Antonia Charalambous; Victoria Mico; Laura E. McVeigh; Gemma Marston; Nicola Ingram; Milène Volpato; Sally A. Peyman; James R. McLaughlan; Antonia Wierzbicki; Paul M. Loadman; Richard J. Bushby; Alexander F. Markham; Stephen D. Evans; P. Louise Coletta

doi:10.1016/j.nano.2021.102401

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

Antonia Charalambous, Victoria Mico, Laura E. McVeigh, Gemma Marston, Nicola Ingram, Milène Volpato, Sally A. Peyman, James R. McLaughlan, Antonia Wierzbicki, Paul M. Loadman, Richard J. Bushby, Alexander F. Markham, Stephen D. Evans, P. Louise Coletta^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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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.

Original language	English
Article number	102401
Journal	Nanomedicine: Nanotechnology, Biology, and Medicine
Volume	36
Early online date	22 Apr 2021
DOIs	https://doi.org/10.1016/j.nano.2021.102401
Publication status	Published - Aug 2021

Keywords

Combretastatin A4
Lipid-Oil-Nanodroplets (LONDs)
Microbubbles
Targeting
Ultrasound trigger

ASJC Scopus subject areas

Bioengineering
Medicine (miscellaneous)
Molecular Medicine
Biomedical Engineering
General Materials Science
Pharmaceutical Science

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Charalambous, A., Mico, V., McVeigh, L. E., Marston, G., Ingram, N., Volpato, M., Peyman, S. A., McLaughlan, J. R., Wierzbicki, A., Loadman, P. M., Bushby, R. J., Markham, A. F., Evans, S. D., & Coletta, P. L. (2021). Targeted microbubbles carrying lipid-oil-nanodroplets for ultrasound-triggered delivery of the hydrophobic drug, combretastatin A4. Nanomedicine: Nanotechnology, Biology, and Medicine, 36, Article 102401. https://doi.org/10.1016/j.nano.2021.102401

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title = "Targeted microbubbles carrying lipid-oil-nanodroplets for ultrasound-triggered delivery of the hydrophobic drug, combretastatin A4",

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.",

keywords = "Combretastatin A4, Lipid-Oil-Nanodroplets (LONDs), Microbubbles, Targeting, Ultrasound trigger",

author = "Antonia Charalambous and Victoria Mico and McVeigh, {Laura E.} and Gemma Marston and Nicola Ingram and Mil{\`e}ne Volpato and Peyman, {Sally A.} and McLaughlan, {James R.} and Antonia Wierzbicki and Loadman, {Paul M.} and Bushby, {Richard J.} and Markham, {Alexander F.} and Evans, {Stephen D.} and Coletta, {P. Louise}",

note = "Publisher Copyright: {\textcopyright} 2021 The Authors",

year = "2021",

month = aug,

doi = "10.1016/j.nano.2021.102401",

language = "English",

volume = "36",

journal = "Nanomedicine: Nanotechnology, Biology, and Medicine",

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Charalambous, A, Mico, V, McVeigh, LE, Marston, G, Ingram, N, Volpato, M, Peyman, SA, McLaughlan, JR, Wierzbicki, A, Loadman, PM, Bushby, RJ, Markham, AF, Evans, SD & Coletta, PL 2021, 'Targeted microbubbles carrying lipid-oil-nanodroplets for ultrasound-triggered delivery of the hydrophobic drug, combretastatin A4', Nanomedicine: Nanotechnology, Biology, and Medicine, vol. 36, 102401. https://doi.org/10.1016/j.nano.2021.102401

TY - JOUR

T1 - Targeted microbubbles carrying lipid-oil-nanodroplets for ultrasound-triggered delivery of the hydrophobic drug, combretastatin A4

AU - Charalambous, Antonia

AU - Mico, Victoria

AU - McVeigh, Laura E.

AU - Marston, Gemma

AU - Ingram, Nicola

AU - Volpato, Milène

AU - Peyman, Sally A.

AU - McLaughlan, James R.

AU - Wierzbicki, Antonia

AU - Loadman, Paul M.

AU - Bushby, Richard J.

AU - Markham, Alexander F.

AU - Evans, Stephen D.

AU - Coletta, P. Louise

PY - 2021/8

Y1 - 2021/8

N2 - 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.

AB - 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.

KW - Combretastatin A4

KW - Lipid-Oil-Nanodroplets (LONDs)

KW - Microbubbles

KW - Targeting

KW - Ultrasound trigger

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U2 - 10.1016/j.nano.2021.102401

DO - 10.1016/j.nano.2021.102401

M3 - Article

C2 - 33894396

AN - SCOPUS:85111073137

SN - 1549-9634

VL - 36

JO - Nanomedicine: Nanotechnology, Biology, and Medicine

JF - Nanomedicine: Nanotechnology, Biology, and Medicine

M1 - 102401

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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