Medical Specialties Commons^™

Development Of A Dual Drug-Loaded, Surfactant-Stabilized Contrast Agent Containing Oxygen, Raj Patel, Quezia Lacerda, Brian E Oeffinger, John R. Eisenbrey, Ankit K. Rochani, Gagan Kaushal, Corinne Wessner, Margaret A Wheatley

Department of Radiology Faculty Papers

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 …

Making Waves: How Ultrasound-Targeted Drug Delivery Is Changing Pharmaceutical Approaches., Lauren J Delaney, Selin Isguven, John R Eisenbrey, Noreen J Hickok, Flemming Forsberg

Department of Radiology Faculty Papers

Administration of drugs through oral and intravenous routes is a mainstay of modern medicine, but this approach suffers from limitations associated with off-target side effects and narrow therapeutic windows. It is often apparent that a controlled delivery of drugs, either localized to a specific site or during a specific time, can increase efficacy and bypass problems with systemic toxicity and insufficient local availability. To overcome some of these issues, local delivery systems have been devised, but most are still restricted in terms of elution kinetics, duration, and temporal control. Ultrasound-targeted drug delivery offers a powerful approach to increase delivery, therapeutic …

Gemcitabine-Loaded Microbubble System For Ultrasound Imaging And Therapy., Lauren J. Delaney, John R. Eisenbrey, David Brown, Jonathan R Brody, Masaya Jimbo, Brian E Oeffinger, Maria Stanczak, Flemming Forsberg, Ji-Bin Liu, Margaret A Wheatley

Department of Radiology Faculty Papers

Ultrasound imaging presents many positive attributes, including safety, real-time imaging, universal accessibility, and cost. However, inherent difficulties in discrimination between soft tissues and tumors prompted development of stabilized microbubble contrast agents. This presents the opportunity to develop agents in which drug is entrapped in the microbubble shell. We describe preparation and characterization of theranostic poly(lactide) (PLA) and pegylated PLA (PEG-PLA) shelled microbubbles that entrap gemcitabine, a commonly used drug for pancreatic cancer (PDAC). Entrapping 6 wt% gemcitabine did not significantly affect drug activity, microbubble morphology, or ultrasound contrast activity compared with unmodified microbubbles. In vitro microbubble concentrations yielding ≥ 500nM …

Shell Effects On Acoustic Performance Of A Drug-Delivery System Activated By Ultrasound., Lauren J Jablonowski, Michael C Cochran, John R. Eisenbrey, Nutte T. Teraphongphom, Margaret A Wheatley

Department of Radiology Faculty Papers

The composition of microcapsules designed for drug delivery significantly impacts their properties. Ultrasound contrast agents, consisting of stabilized microbubbles (MBs), have emerged as versatile potential drug delivery vehicles to both image and overcome challenges associated with systemic chemotherapy. In our development of polylactic acid MBs decorated with immune-shielding polyethylene glycol chains, we have shown that the balance between acoustic behavior and immune avoidance was scalable and amenable to two distinct PEGylation methods, either incorporation of 5 wt% PEGylated PLA or insertion of 1 wt% PEGylated lipid (LipidPEG) in the polymeric shell. Here we describe the effects of shell compositions on …

Effect Of Pulse Shaping On Subharmonic Aided Pressure Estimation In Vitro And In Vivo., Ipshita Gupta, John R. Eisenbrey, Maria Stanczak, Anush Sridharan, Jaydev K. Dave, Ji-Bin Liu, Christopher Hazard, Xinghua Wang, Ping Wang, Huiwen Li, Kirk Wallace, Flemming Forsberg

Department of Radiology Faculty Papers

OBJECTIVES: Subharmonic imaging (SHI) is a technique that uses the nonlinear oscillations of microbubbles when exposed to ultrasound at high pressures transmitting at the fundamental frequency ie, f

METHODS: Eight waveforms with different envelopes were optimized with respect to acoustic power at which the SHAPE study is most sensitive. The study was run with four input transmit cycles, first in vitro and then in vivo in three canines to select the waveform that achieved the best sensitivity for detecting changes in portal pressures using SHAPE. A Logiq 9 scanner with a 4C curvi-linear array was used to acquire 2.5 MHz …