Anthracycline Binding and Release from the Natural Biopolymer Chondroitin Sulfate for Cancer Treatment

There will be an estimated 600,000 deaths this year alone from cancer in the US. Chemotherapy, while critical to many cancer therapy regimes, has many negative side effects as it is generally non-specific and targets all proliferative cells. Local delivery has the potential to allow for higher drug concentrations at the tumor site, while minimizing systemic toxicity. Injectable photocrosslinked hydrogels may be used for local delivery. Chondroitin sulfate (CS) is a sulfated glycosaminoglycan that has many promising properties, including biocompatibility and anionic groups, allowing for binding with cationic chemotherapy drugs such as doxorubicin and sunitinib through electrostatic interactions.[1] CS can be modified with photocrosslinkable methacryloyl groups for injectable hydrogel fabrication (CSMA). These hydrogels are tunable, allowing for the manipulation of physical and mechanical properties that may be used to tune drug release kinetics. Their ability to bind and slowly release cationic drugs allows them to be an ideal system for local chemotherapeutic delivery. However, a fundamental understanding of how cationic drugs bind beyond simple electrostatic interactions and the impact on drug release is not fully understood. In this work, characterized binding and release of doxorubicin and daunorubicin, two anthracycline drugs that are structurally similar with a single difference in a hydroxyl group present in doxorubicin replaced by a hydrogen in daunorubicin. We found that the drug binding on a mole per mass of CSMA hydrogel is similar. However, the release kinetics are vastly different attributed to the hydroxyl group. Using UV/vis and ultra-fast transient absorption spectroscopy techniques, we investigated drug binding to CS polymer in solution to develop an understanding of the drug binding mechanisms and polymer or drug structural changes. By developing this fundamental understanding of drug/CS interaction, we will begin to address our long-term goal to develop intra-tumoral drug delivery systems as adjuvant therapies for cancer treatment.<br/><br/>References:<br/>[1]Ornell, <b><i>J. Mater. Chem. B</i></b>, 2019,<b>7</b>,2151-2161