Mr. Selva Jeganathan Profile

Selva Jeganathan

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Proceedings Article | 19 February 2020 Presentation + Paper

Dye diffusion proximal to in situ forming implants is increased by ultrasound stimulation

Elizabeth S. Berndl, Emily Budziszewski, Selva Jeganathan, Agata Exner, Michael Kolios

Proceedings Volume 11219, 112190L (2020) https://doi.org/10.1117/12.2547061

KEYWORDS: Diffusion, Ultrasonography, Polymerization, Calibration, Transducers, Tumors, Molecules, Biomedical engineering

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Chemotherapeutics are generally delivered systemically, causing damage to rapidly dividing cells and leading to a compromised immune system, nausea, fatigue, and hair loss. In situ forming implants (ISFIs) are biocompatible drug delivery vehicles which are injected as a liquid, undergo phase inversion during drug delivery, and ultimately breakdown, thereby allowing for localized release of drugs, potentially reducing side effects of chemotherapeutics.

Previous experiments in our lab have shown that applying one-time ultrasound to ISFIs loaded with chemotherapeutics, shortly after injection, the 8-day release of doxorubicin can increase from 60% to 95% in vivo. To separate the effects of sonication on the effective drug diffusion rate from those related to how the US exposure may change the phase inversion kinetics and drug release, ISFIs and reservoirs of Janus Green B dye, located approximately 6 mm apart, were embedded in a polyacrylamide phantom. ISFIs were stimulated with a 1 MHz focused transducer with either no, mild (10 min, 10% duty), or intense (5 min, 33% duty) sonication, and phantoms were imaged to determine diffusion rates.

The relative diffusion area and dye diffusion rate were analysed as a function of time, regions enclosed by a thresholding contour line and sonication type. Compared to the no sonication control, the effects of mild sonication were variable, with relative area increasing in low concentration contours and decreasing at high concentration contours (p = 0.0002). Intense sonication, compared to no sonication, had increased dye diffusion rate (p= 0.014), and a decrease in the relative area at early time points, and an increase at later time points (p = 0.041).

The results suggest that high intensity ultrasound exposure on a nearby object can cause changes to the diffusion of molecules located in the proximity of the object.

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