Sustained release of curcumin from fibrin matrix induces cancer cell death and immunomodulation

Abstract

Despite the role of curcumin in controlling inflammation, angiogenesis, and cancer in human cells, its therapeutic use is limited. The reasons are quick metabolic breakdown, low aqueous solubility, and bioavailability. This study describes the advantages of clinical-grade curcumin-incorporated fibrin matrix either in lyophilized off-the-shelf wafer or injectable hydrogel forms, as a biodegradable local delivery system. To produce the curcumin-fibrin wafer, used clinical-grade fibrin sealant in a modified composition. To fabricate wafer, we premixed the curcumin with either fibrinogen or thrombin, before clotting into a hydrogel. Sustained release of active curcumin from fibrin wafer, suspended in culture medium at 37 °C lasted for seven days. Upon premixing albumin with thrombin and subsequently adding curcumin into the mixture improved the loading concentration and stability. Dose- and time-dependent apoptotic function of curcumin on cancer cell lines upon release from fibrin wafer, were demonstrated in vitro. In vivo immuno-modulation and a nontoxic response to curcumin released from fibrin into the peritoneal cavity of mice were established. The cytotoxic effect of released curcumin was demonstrated; showing both a preventive and therapeutic role against tumor growth. In vivo studies used Dalton's Lymphoma Ascites (DLA) mice model. Both implanted fibrin wafer and injected hydrogel can breakdown by a physiological process and get cleared by the fibrinolytic mechanism. The lyophilized fibrin wafer could function as a hemostat, adhere to surgical cancer tissues, and arrest bleeding. The potential of curcumin in preventing solid tumor metastasis may be explored upon the sustained delivery of the molecule from the fibrin wafer.