Poster G9 - Characterizing the Release Rate of Ethanol from Polymer-Assisted Ethanol Ablation

Thursday, October 24, 2024

2:45 PM – 3:45 PM EST

Location: Exhibit Hall E, F & G

Presenting Author(s)

Peter Shin

Undergraduate Researcher
Mueller Lab
Silver Spring, Maryland, United States

Co-Author(s)

Jeffrey Yang (he/him/his)

Graduate Research Assistant
University of Maryland, College Park
College Park, Maryland, United States

Primary Investigator(s)

Jenna Mueller, PhD (she/her/hers)

Assistant Professor
University of Maryland
College Park, Maryland, United States

Introduction: Surgical excision is at the foundation of cancer treatment. Many patients are ineligible for surgical treatment, however, depending on tumor stage and location [1]. Ethanol ablation offers an effective alternative in which pure ethanol is directly injected into the tumor to induce tissue necrosis [1]. However, ethanol tends to leak out of the injection site and can cause off target effects and complications. To address this leakage problem, we have previously combined a biocompatible polymer, ethyl cellulose (EC), with ethanol to create a viscous gel when injected in tissue, which largely reduces ethanol leakage from the injection site [2]. This study investigates the ability to modulate the release rate of ethanol from EC-ethanol.

Materials and

Methods: Figure 1A describes the custom Franz Cell apparatus (4G-01-01-11.28-08, PermeGear Inc., Hellertown, PA) used to measure the release rate of ethanol. We ran two different groups of experiments: 1500uL of pure ethanol or 1500uL of EC-ethanol (6% w/v, 200 proof ethanol, n=5 repeats for both groups) were added to the donor chamber and allowed to diffuse, through the polyvinylidene fluoride membrane (PVDF, HVLP02500 Durapore, Sigma, St.Louis, MO) into deionized water contained in the receptor chamber. A stir bar was placed inside the receptor chamber and set to 200 rpm to mimic blood circulation through the body [3]. Then, 500uL samples were collected at specific time points (0 – 120 minutes) through the sampling port with the same volume of deionized water replenished to the receptor chamber immediately after. The relative fluorescence units (RFU) of ethanol in each sample was determined via ethanol fluorescence quantification kit (40001, Amplite®, AAT Bioquest, Pleasanton, CA). Standard curves with known concentrations of ethanol were also measured with the microplate reader to interpolate sample RFU measurements to concentration. Concentration curves were then used to calculate the diffusion coefficients (a common procedure for which Franz cells are used) [3].

Results, Conclusions, and Discussions: The average fluorescence intensity and concentration for pure ethanol and EC-ethanol are shown in Figure 1B and 1C, respectively. Starting at 20 minutes, the ethanol readings for the pure ethanol group began increasing at a higher rate than that of EC-ethanol, suggesting that the presence of EC drastically slowed the release rate of ethanol. The diffusion coefficients for pure ethanol and EC-ethanol were 1.4e-10 and 3.0e-11, respectively, corroborating the observation that EC slowed ethanol diffusion by a factor of 4.6. Future work includes varying EC concentrations to further demonstrate how we can control drug release kinetics through modulating EC content of EC-ethanol. Ultimately, this information will be used to select the optimal EC concentration for intratumoral administration in cancer patients of all settings.

Acknowledgements (Optional): This study was funded by the NSF (NSF CAREER 2339554) and University of Maryland startup funds.

References:
Quang et al, Bioengineering, 2023. 10(11): 1246.
Morhard et al, Scientific reports, 2017. 7(1): 8750.
Yang, J., Bioeng Transl Med, 2024. e10696.
Franz cell - the original. PermeGear. (2022).