Incubation Method for Loading Lonidamine in Oxygen Microbubbles for Targeted Drug Delivery
| Autor: | Patrick O'Kane, Flemming Forsberg, Gagan Kaushal, Margaret A. Wheatley, John R. Eisenbrey, Raj Patel, Brian E. Oeffinger, Quezia Lacerda, Ankit K. Rochani, Dennis B. Leeper |
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| Rok vydání: | 2020 |
| Předmět: |
Pulsatile flow
Lonidamine 02 engineering and technology 021001 nanoscience & nanotechnology Micelle Bioavailability 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine chemistry 030220 oncology & carcinogenesis Drug delivery Microbubbles 0210 nano-technology Incubation Mechanical index Biomedical engineering |
| Zdroj: | 2020 IEEE International Ultrasonics Symposium (IUS). |
| DOI: | 10.1109/ius46767.2020.9251788 |
| Popis: | Lonidamine (LND) has been widely explored due to its ability to target metabolic glycolysis and mitochondrial respiration in tumors [4]. However, clinical translation has stalled due to poor bioavailability after oral administration. In this study, we explored three incubation time points of loading oxygen-filled microbubbles with LND (SE61O2-LND) for radiotherapy sensitization by modifying our published methods for creating surfactant-shelled oxygen microbubbles (SE61 O2). Acoustic enhancement and stability were quantified in vitro in a continuously insonated sample holder using a 5 MHz single element transducer which generated a peak positive pressure of 0.69 MPa and a peak negative pressure of 0.25 MP at a PRF of 100 Hz and in a pulsatile flow phantom insonated at a single point using a C1-6 transducer on a GE Logiq E9 system (GE Healthcare) operating at 4.0 MHz at a mechanical index of 0.12. Flow cytometry was performed to analyze the total bubble count for each incubation time point. Lonidamine encapsulation was determined using liquid chromatography-mass spectrometry (LC-MS), the loading approach consisted of incubating the LND and TPGS at 37°C at 0, 24, and 48 hours. Bubbles incubated for 24 hours had an average encapsulation of 2.64 ± 0.32 µg LND/ mL MB, and those incubated for 48 hours had an average of 2.97 ± 0.36 µg LND/ mL MB, while non-incubated micelles had an average of 1.51 ± 0.05 µg LND/ mL MB, both TPGS micelle methods that were incubated showed a statistically significant improvement p < 0.001 compared to non-incubated. This work demonstrates the feasibility of fabricating lonidamine-loaded microbubbles and an improved approach for increasing drug encapsulation. The microbubbles retained their acoustic properties, and by incubating the lonidamine with the TPGS to form micelles, drug loading was increased. |
| Databáze: | OpenAIRE |
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