Formulating Thermosensitive Radiopaque Hydrogel for Hepatocellular Carcinoma Treatment

Ananyaa Kumar

Students

Engineering and Applied Sciences

Faculty

Assistant Professor of Radiology

Project Summary

This summer I worked in the Cormode lab on developing novel formulations of radiopaque hydrogels that could be used to treat hepatocellular carcinoma with higher efficacy than currently existing therapies, which have a sub 30% 5-year survival rate. This injectable hydrogel will cause ischemia at the tumor site to block blood flow to the tumor, and release the lactate dehydrogenase inhibitor NHI 2 to shrink the tumor. It also contains gold nanoparticles (AuNP) to provide X-ray contrast to monitor the hydrogel as it is deployed and as it degrades in the body.

The hydrogels contain chitosan, a biocompatible and biodegradable polymer, and ammonium hydrogen phosphate (AHP) crosslinker; the mixture of these two compounds is liquid at room temperature and gels at the body’s internal temperature of 37 degrees Celsius. I developed and tested several formulations of hydrogels containing chitosan, AHP, AuNP, and NHI 2 until I developed a formulation of a 1 mL hydrogel that gelled at 37 degrees Celsius between 1 to 2 minutes, which is the ideal hydrogel volume and gelation time for in-vivo testing in rat models. This formulation had a chitosan to AHP ratio of 0.16. I concluded that AuNP and NHI 2 do not have an effect on the gelation time of the hydrogel, and that gelation time can be entirely controlled by the ratio of chitosan to AHP, with greater amounts of AHP allowing the hydrogel to gel faster. I also did a cell viability assay of NHI 2 on HUH 7 cells, a liver cell line, and confirmed that NHI 2 is toxic to the cells, as predicted. I plan on testing the developed formulation in-vivo in rat models in the coming weeks to confirm that the hydrogel gels and degrades as expected inside the vasculature.

As a bioengineering student, I took a biomaterials class which discussed the theory of the hydrogel as a part of my curriculum. Actually making and testing hydrogels allowed me to understand and translate what I had learned in class to the lab, enriching my experience. Other than the science behind and procedure for how to develop a hydrogel, I learned about how to do cell research, including reviving and passaging cells, and conducting cell viability assays on them. I also completed inductively coupled plasma - optical emission spectrometry training and mouse training during this time. Through this research experience I learned about the time management and organizational skills needed to meet research goals largely independently, and about the dynamics and expectations of lab work. Doing this project and working in the lab has shown me that I want to continue doing research as a part of my career.

To see my poster, please visit Penn Presents: https://presentations.curf.upenn.edu/poster/formulating-thermosensitive-...