Hydrogel loaded with self-assembled dextran sulfate-doxorubicin complexes as a delivery system for chemotherapy

Abstract

Standard clinical care for breast cancer includes lumpectomy followed by localized radiotherapy or chemotherapy. However, both therapies cause loss of normal, healthy tissue in addition to tumor tissue, leading to undesirable side effects. In this study, we found that low dose and prolonged treatment with anticancer drug doxorubicin (DOX) can completely eliminate MDA-MB-231 breast cancer cells with low cytotoxicity to NIH 3T3 fibroblasts. We further developed a novel biomaterial-based drug delivery system for controlled and sustained release of low doses of DOX based on self-assembled dextran sulfate (DS)-DOX complexes. We found that adding divalent metal ions in the complex can improve the entrapment efficiency of DOX and prolong DOX release. We encapsulated the DS-DOX complexes into biocompatible, biodegradable, and injectable agarose hydrogel. The hydrogel can be injected into the cavity after lumpectomy for sustained local delivery of low-dose DOX. Cell viability experiments confirmed that this drug delivery system completely eliminated MDA-MB-231 cancer cells while maintaining the viability of NIH 3T3 fibroblasts at the end of treatment. Thus, this novel drug delivery system represents a promising approach for local chemotherapy to improve locoregional control of breast cancer.