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Article

Development of a Dual Drug-Loaded, Surfactant-Stabilized Contrast Agent Containing Oxygen

1
School of Biomedical Engineering Science and Health Systems, Drexel University, Philadelphia, PA 19104, USA
2
Department of Radiology, Thomas Jefferson University, Philadelphia, PA 19107, USA
3
Department of Pharmaceutical Sciences, Thomas Jefferson University, Philadelphia, PA 19107, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Iolanda De Marco
Polymers 2022, 14(8), 1568; https://doi.org/10.3390/polym14081568
Received: 7 March 2022 / Revised: 1 April 2022 / Accepted: 7 April 2022 / Published: 12 April 2022
Co-delivery of cancer therapeutics improves efficacy and encourages synergy, but delivery faces challenges, including multidrug resistance and spatiotemporal distribution of therapeutics. To address these, we added paclitaxel to previously developed acoustically labile, oxygen-core, surfactant-stabilized microbubbles encapsulating lonidamine, with the aim of developing an agent containing both a therapeutic gas and two drugs acting in combination. Upon comparison of unloaded, single-loaded, and dual-loaded microbubbles, size (~1.7 µm) and yield (~2 × 109 microbubbles/mL) (~1.7) were not statistically different, nor were acoustic properties (maximum in vitro enhancements roughly 18 dB, in vitro enhancements roughly 18 dB). Both drugs encapsulated above required doses calculated for head and neck squamous cell carcinoma, the cancer of choice. Interestingly, paclitaxel encapsulation efficiency increased from 1.66% to 3.48% when lonidamine was included. During preparation, the combination of single drug-loaded micelles gave higher encapsulation (µg drug/g microbubbles) than micelles loaded with either drug alone (lonidamine, 104.85 ± 22.87 vs. 87.54 ± 16.41), paclitaxel (187.35 ± 8.38 vs. 136.51 ± 30.66). In vivo intravenous microbubbles produced prompt ultrasound enhancement within tumors lasting 3–5 min, indicating penetration into tumor vasculature. The ability to locally destroy the microbubble within the tumor vasculature was confirmed using a series of higher intensity ultrasound pulses. This ability to locally destroy microbubbles shows therapeutic promise that warrants further investigation. View Full-Text
Keywords: ultrasound contrast agent; microbubbles; theranostic agents; ultrasound-triggered drug delivery; dual drug loading; surfactant; oxygen delivery ultrasound contrast agent; microbubbles; theranostic agents; ultrasound-triggered drug delivery; dual drug loading; surfactant; oxygen delivery
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MDPI and ACS Style

Patel, R.; Lacerda, Q.; Oeffinger, B.E.; Eisenbrey, J.R.; Rochani, A.K.; Kaushal, G.; Wessner, C.E.; Wheatley, M.A. Development of a Dual Drug-Loaded, Surfactant-Stabilized Contrast Agent Containing Oxygen. Polymers 2022, 14, 1568. https://doi.org/10.3390/polym14081568

AMA Style

Patel R, Lacerda Q, Oeffinger BE, Eisenbrey JR, Rochani AK, Kaushal G, Wessner CE, Wheatley MA. Development of a Dual Drug-Loaded, Surfactant-Stabilized Contrast Agent Containing Oxygen. Polymers. 2022; 14(8):1568. https://doi.org/10.3390/polym14081568

Chicago/Turabian Style

Patel, Raj, Quezia Lacerda, Brian E. Oeffinger, John R. Eisenbrey, Ankit K. Rochani, Gagan Kaushal, Corinne E. Wessner, and Margaret A. Wheatley. 2022. "Development of a Dual Drug-Loaded, Surfactant-Stabilized Contrast Agent Containing Oxygen" Polymers 14, no. 8: 1568. https://doi.org/10.3390/polym14081568

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