학술논문
Evaluation of Loading Strategies to Improve Tumor Uptake of Gemcitabine in a Murine Orthotopic Bladder Cancer Model Using Ultrasound and Microbubbles.
Document Type
Academic Journal
Author
Ruan JL; MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, United Kingdom.; Browning RJ; Institute of Biomedical Engineering, University of Oxford, Oxford, United Kingdom.; Yildiz YO; MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, United Kingdom.; Bau L; Institute of Biomedical Engineering, University of Oxford, Oxford, United Kingdom.; Kamila S; Biomedical Sciences Research Institute, University of Ulster, Coleraine, Northern Ireland, United Kingdom.; Gray MD; Institute of Biomedical Engineering, University of Oxford, Oxford, United Kingdom.; Folkes L; MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, United Kingdom.; Hampson A; MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, United Kingdom.; McHale AP; Biomedical Sciences Research Institute, University of Ulster, Coleraine, Northern Ireland, United Kingdom.; Callan JF; Biomedical Sciences Research Institute, University of Ulster, Coleraine, Northern Ireland, United Kingdom.; Vojnovic B; MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, United Kingdom.; Kiltie AE; MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, United Kingdom.; Stride E; Institute of Biomedical Engineering, University of Oxford, Oxford, United Kingdom. Electronic address: eleanor.stride@eng.ox.ac.uk.
Source
Publisher: Pergamon Press Country of Publication: England NLM ID: 0410553 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-291X (Electronic) Linking ISSN: 03015629 NLM ISO Abbreviation: Ultrasound Med Biol Subsets: MEDLINE
Subject
Language
English
Abstract
In this study we compared three different microbubble-based approaches to the delivery of a widely used chemotherapy drug, gemcitabine: (i) co-administration of gemcitabine and microbubbles (Gem+MB); (ii) conjugates of microbubbles and gemcitabine-loaded liposomes (GemlipoMB); and (iii) microbubbles with gemcitabine directly bound to their surfaces (GembioMB). Both in vitro and in vivo investigations were carried out, respectively, in the RT112 bladder cancer cell line and in a murine orthotopic muscle-invasive bladder cancer model. The in vitro (in vivo) ultrasound exposure conditions were a 1 (1.1) MHz centre frequency, 0.07 (1.0) MPa peak negative pressure, 3000 (20,000) cycles and 100 (0.5) Hz pulse repetition frequency. Ultrasound exposure produced no significant increase in drug uptake either in vitro or in vivo compared with the drug-only control for co-administered gemcitabine and microbubbles. In vivo, GemlipoMB prolonged the plasma circulation time of gemcitabine, but only GembioMB produced a statistically significant increase in cleaved caspase 3 expression in the tumor, indicative of gemcitabine-induced apoptosis.
Competing Interests: conflict of interest statement John Callan, Anthony McHale and Eleanor Stride are co-founders of a spin out company, SonoTarg Ltd. and inventors on a patent (US20180344872A1) which covers one of the formulations reported in this paper. There was, however, no involvement of SonoTarg in the design, conduct or funding of this study and SonoTarg is not currently pursuing applications in chemoradiation therapy.
(Copyright © 2021 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)
Competing Interests: conflict of interest statement John Callan, Anthony McHale and Eleanor Stride are co-founders of a spin out company, SonoTarg Ltd. and inventors on a patent (US20180344872A1) which covers one of the formulations reported in this paper. There was, however, no involvement of SonoTarg in the design, conduct or funding of this study and SonoTarg is not currently pursuing applications in chemoradiation therapy.
(Copyright © 2021 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)