Self-Assembled Doxorubicin-Dextran Sulfate Complexes in Hydrogel as Delivery System for Chemotherapy Following Breast Tumor Removal

Abstract

Standard clinical care for early stage breast cancer includes lumpectomy followed by localized radiotherapy to achieve long-term remission. However, radiation therapy can cause serious side effects including buildup of lymph fluid that limits operative healing, and long-term health complications. Alternatively, chemotherapeutic drugs can be administered following lumpectomy. However, the chemotherapeutic drugs can cause a 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 effectively kill 100% MDA-MB-231 breast cells while exhibited no significant cytotoxicity to NIH 3T3 fibroblasts. We further developed a novel drug delivery system for controlled and sustained release of low dose of DOX based on self-assembled DOX-dextran sulfate (DS) complexes. We found that adding divalent metal ions in the complex can improve the entrapment efficiency of DOX and prolong DOX release. Biocompatible, biodegradable, and injectable hydrogels agarose and agarose/methylcellulose were used to encapsulate the DOX-DS complex. The hydrogels 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 cells while maintained the viability of NIH 3T3 fibroblasts at the end of treatment. Thus, this novel drug delivery system represents a promising approach for localized chemotherapy to improve locoregional control of breast cancer.%%%%M.S., Biological Sciences – Drexel University, 2013