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dc.contributor.authorCharalambous, A.
dc.contributor.authorMico, V.
dc.contributor.authorMcVeigh, L.E.
dc.contributor.authorMarston, G.
dc.contributor.authorIngram, N.
dc.contributor.authorVolpato, M.
dc.contributor.authorPeyman, S.A.
dc.contributor.authorMcLaughlan, J.R.
dc.contributor.authorWierzbicki, Antonia
dc.contributor.authorLoadman, Paul M.
dc.contributor.authorBushby, R.J.
dc.contributor.authorMarkham, A.F.
dc.contributor.authorEvans, S.D.
dc.contributor.authorColetta, P.L.
dc.date.accessioned2021-06-11T08:12:48Z
dc.date.accessioned2021-06-23T15:30:39Z
dc.date.available2021-06-11T08:12:48Z
dc.date.available2021-06-23T15:30:39Z
dc.date.issued2021-08
dc.identifier.citationCharalambous 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.en_US
dc.identifier.urihttp://hdl.handle.net/10454/18516
dc.descriptionYesen_US
dc.description.abstractThe 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.en_US
dc.description.sponsorshipThe work was funded by the Medical Research Council (grant number: MR/L01629X MRC Medical Bioinformatics Centre) and the EPSRC (grant number EP/P023266/1 Health Impact Partnership). EPSRC (EP/I000623/1, EP/K023845/1). Laura E. McVeigh was funded by an EPSRC PhD Studentship (EP/L504993/1).en_US
dc.language.isoenen_US
dc.relation.isreferencedbyhttps://doi.org/10.1016/j.nano.2021.102401en_US
dc.rights© 2021 The Authors. Published by Elsevier Inc. under a Creative Commons license (https://creativecommons.org/licenses/by/4.0/).en_US
dc.subjectLipid-Oil-Nanodroplets (LONDs)en_US
dc.subjectCombretastatin A4en_US
dc.subjectMicrobubblesen_US
dc.subjectTargetingen_US
dc.subjectUltrasound triggeren_US
dc.titleTargeted microbubbles carrying lipid-oil-nanodroplets for ultrasound-triggered delivery of the hydrophobic drug, Combretastatin A4en_US
dc.status.refereedYesen_US
dc.date.Accepted2021-03
dc.date.application2021-04-22
dc.typeArticleen_US
dc.type.versionPublished versionen_US
dc.date.updated2021-06-11T07:13:01Z
refterms.dateFOA2021-06-23T15:32:48Z
dc.openaccess.statusGolden_US


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