Doxorubicin-loaded silk films: Drug-silk interactions and in vivo performance in human orthotopic breast cancer

Breast cancer is the most common of all malignant diseases in women. Systemic chemotherapy provides low clinical benefit for locoregional control of the disease, while localised chemotherapy may provide a therapeutic advantage. In this study, doxorubicin-loaded silk films were directly applied to tumours. Affinity binding studies demonstrated that the adsorption of doxorubicin onto silk was partially dependent on crystallinity. By manipulating silk crystallinity, or beta-sheet content, the doxorubicin release rate could be controlled ranging from immediate release to prolonged release over >4 weeks. The therapeutic impact of doxorubicin-loaded silk films on primary tumour growth and metastasis was assessed in mice using a humanised orthotopic breast cancer model (adenocarcinoma). Both soluble and stabilised silk films loaded with doxorubicin had a significantly greater primary tumour response than the equivalent dose of doxorubicin administered intravenously in the absence of the silk film carrier. In addition to reducing primary tumour growth, stabilised silk films loaded with doxorubicin also reduced metastatic spread and autopsy indicated that these films were not associated with any local or systemic toxicities. Collectively, these results suggest that the future use of this approach for localised chemotherapy is promising. (C) 2012 Elsevier Ltd. All rights reserved.