Targeted microbubbles carrying lipid-oil-nanodroplets for ultrasound-triggered delivery of the hydrophobic drug, Combretastatin A4
| Autor: | 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. |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: | |
| Druh dokumentu: | Článek |
| DOI: | 10.1016/j.nano.2021.102401 |
| Popis: | Yes 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. The 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). |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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