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Accepted (AM)Open Access (License Unspecified), Open
Journal article
Tumoral oxygenation and biodistribution of Lonidamine oxygen microbubbles following localized ultrasound-triggered delivery
International journal of pharmaceutics, v 625, 122072
25 Sep 2022
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
[Display omitted]
•Microbubble-assisted delivery of oxygen.•Lonidamine prolongs the elevated oxygen levels.•High intensity destructive ultrasound pulses.
Prior work has shown that microbubble-assisted delivery of oxygen improves tumor oxygenation and radiosensitivity, albeit over a limited duration. Lonidamine (LND) has been investigated because of its ability to stimulate glycolysis, lactate production, inhibit mitochondrial respiration, and inhibit oxygen consumption rates in tumors but suffers from poor bioavailability. The goal of this work was to characterize LND-loaded oxygen microbubbles and assess their ability to oxygenate a human head and neck squamous cell carcinoma (HNSCC) tumor model, while also assessing LND biodistribution. In tumors treated with surfactant-shelled microbubbles with oxygen core (SE61O2) and ultrasound, pO2 levels increased to a peak 19.5 ± 9.7 mmHg, 50 s after injection and returning to baseline after 120 s. In comparison, in tumors treated with SE61O2/LND and ultrasound, pO2 levels showed a peak increase of 29.0 ± 8.3 mmHg, which was achieved 70 s after injection returning to baseline after 300 s (p < 0.001). The co-delivery of O2andLNDvia SE61 also showed an improvement of LND biodistribution in both plasma and tumor tissues (p < 0.001). In summary, ultrasound-sensitive microbubbles loaded with O2 and LND provided prolonged oxygenation relative to oxygenated microbubbles alone, as well as provided an ability to locally deliver LND, making them more appropriate for clinical translation.
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Details
- Title
- Tumoral oxygenation and biodistribution of Lonidamine oxygen microbubbles following localized ultrasound-triggered delivery
- Creators
- Quezia Lacerda - Thomas Jefferson UniversityAnkit Rochani - Department of Pharmaceutical Sciences, Thomas Jefferson University, Philadelphia, PA 19107, USABrian Oeffinger - School of Biomedical Engineering, Science and Heath Systems, Drexel University, Philadelphia, PA 19104, USAJi-Bin Liu - Department of Radiology, Thomas Jefferson University, Philadelphia, PA 19107, USACorinne E. Wessner - Department of Radiology, Thomas Jefferson University, Philadelphia, PA 19107, USAAylin Tahmasebi - Department of Radiology, Thomas Jefferson University, Philadelphia, PA 19107, USAHebah Falatah - Department of Radiology, Thomas Jefferson University, Philadelphia, PA 19107, USAPhilip Lee - Department of Radiology, Thomas Jefferson University, Philadelphia, PA 19107, USADennis B. Leeper - Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, PA 19107, USAFlemming Forsberg - Department of Radiology, Thomas Jefferson University, Philadelphia, PA 19107, USAJoseph Curry - Department of Radiology, Thomas Jefferson University, Philadelphia, PA 19107, USAScott W. Keith - Division of Biostatistics, Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, PA 19107, USAPatrick O'Kane - Department of Radiology, Thomas Jefferson University, Philadelphia, PA 19107, USAGagan Kaushal - Department of Pharmaceutical Sciences, Thomas Jefferson University, Philadelphia, PA 19107, USAMargaret A. Wheatley - Drexel UniversityJohn R. Eisenbrey - Department of Radiology, Thomas Jefferson University, Philadelphia, PA 19107, USA
- Publication Details
- International journal of pharmaceutics, v 625, 122072
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000877472300002
- Scopus ID
- 2-s2.0-85135951720
- Other Identifier
- 991019173956004721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Pharmacology & Pharmacy