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

Authors

Raj Patel, Drexel University
Quezia Lacerda, Drexel University
Brian E Oeffinger, Drexel University
John R. Eisenbrey, Thomas Jefferson UniversityFollow
Ankit K. Rochani, Thomas Jefferson UniversityFollow
Gagan Kaushal, Thomas Jefferson UniversityFollow
Corinne Wessner, Thomas Jefferson UniversityFollow
Margaret A Wheatley, Drexel University

Document Type

Article

Publication Date

4-12-2022

Comments

This article is the author’s final published version in Polymers, Volume 14, Issue 8, April 2022, Article number 1568.

The published version is available at https://doi.org/10.3390/polym14081568. Copyright © Patel et al.

Abstract

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.

Recommended Citation

Patel, Raj; Lacerda, Quezia; Oeffinger, Brian E; Eisenbrey, John R.; Rochani, Ankit K.; Kaushal, Gagan; Wessner, Corinne; and Wheatley, Margaret A, "Development of a Dual Drug-Loaded, Surfactant-Stabilized Contrast Agent Containing Oxygen" (2022). Department of Radiology Faculty Papers. Paper 123.
https://jdc.jefferson.edu/radiologyfp/123

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.

PubMed ID

35458319

Language

English