Master’s Project Defense
Wednesday, April 24, 2024
50 Prescott Street, 1226
3:30pm — 4:00pm
“Localized Drug Delivery Systems: Applications of Chondroitin Sulfate-based Hydrogels in the Development of Cancer Therapeutic”
Andrew Voronin
Abstract: In 2024, the number of cancer deaths is projected to reach 611,720 along with 2,001,140 new cancer cases in the United States. The current gold standard in chemotherapy lacks the benefits of localized treatment causing the patient to endure a long and energy-draining experience. To combat this, the development of hydrogels can be used for localized drug delivery. Chondroitin sulfate (CS) is biocompatible, naturally abundant component of the ECM found to support hydrogel systems through means of chemical crosslinking. This work investigated injectable furan-modified chondroitin sulfate/maleimide-modified polyethylene glycol (CS-F/PEG-MI) hydrogels for localized delivery of doxorubicin (DOX) and daunorubicin (DNR). Three formulations of varying furan substitution were achieved yielding degrees of substitution (DOS) of 72.0 ± 3.6, 90.0 ± 3.0, and a DOS of 81.0 ± 4.6 %. It was found that there was an overall increase in DOS when increasing furfurylamine content by 2x and 4x, respectively, however a drop-off in DOS was observed at 4x. Swelling studies showed an initial spike in hydrogel weight after 1 day in PBS, followed by a plateau over a 13-day study across all formulations. Average injection force yielded 28.4 ± 4.2 N in the low DOS formulation and a 17.4 ± 1.7 N in the high DOS. DNR loaded hydrogels exhibited higher drug loading profiles on average than DOX, however DNR also released from the hydrogels faster than DOX. Sterile non-drug loaded hydrogel biocompatibility testing resulted in cell viabilities of 79.8 ± 5.8, 88.4 ± 12.5, and 82.3 ± 10.9 % for the low, high, medium DOS formulations, respectively. Direct cytotoxicity testing of DOX and DNR loaded hydrogels showed effectiveness in maintaining cytotoxicity for SK-N-AS cells after 4 days of drug release. Overall, this work showed the applicability of injectable chondroitin sulfate-based hydrogels for the development of localized drug delivery systems.
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Thesis Advisor: |
Defense Committee: |
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Jeannine Coburn, PhD Associate Professor Biomedical Engineering Worcester Polytechnic Institute |
Catherine Whittington, PhD (Chair) Assistant Professor Biomedical Engineering Worcester Polytechnic Institute |
Christina Bailey-Hytholt, PhD Assistant Professor Chemical Engineering Worcester Polytechnic Institute |