Improving drug delivery for hepatocellular carcinoma
The growth and progression of HCC depends on the formation of new blood vessels, or angiogenesis. HCC is a highly vascularised cancer, primarily fed by the hepatic arteries; normal liver tissue receives blood mostly from the portal vein. This makes antiangiogenic treatment a promising HCC therapy. Funded by the EU, the 'Microencapsdelivery' (MICROENCAPSDELIVERY) project aimed to achieve microencapsulation of angiogenesis inhibitors (sorafenib and cilengitide) for their continuous and localised delivery. Alginate beads of tuneable sizes contained the angiogenesis inhibitors and were tested in vitro and in vivo. Scientists used 3D vascularised tumour spheroids to model drug delivery and investigate cell-cell and cell-matrix interactions. The project identified the efficient concentrations of sorafenib and cilengitide by multiple in vitro tests. In addition to 3D tumour spheroid, organotypic cell culture model, aortic ring assay and 2D cell culture assays preceded in vivo experiments. Validation on the chorioallantoic membrane of the chick embryo confirmed the potential of the approach. In vivo experiments of microencapsulated sorafenib-cilengitide on chemically induced HCC rat models will advance the developed therapy to bring it one step closer to clinical trials. While sorafenib is approved by the United States Food and Drug Administration (FDA) for the treatment of patients with advanced HCC, it has a high adverse rate due to toxic side-effects. Development of microencapsulation-based therapeutic options will allow limiting drug delivery specifically to tumours and reduce the side-effects. The new therapeutic platform developed by MICROENCAPSDELIVERY gives hope for a more efficient anticancer antiangiogenic therapy with reduced side-effects.
