LY2109761-LOADED MICROCAPSULES AS DRUG DELIVERY SYSTEM TO INHIBIT THE TGF-B1 PATHWAY IN HEPATOCELLULAR CARCINOMA

Hepatocellular carcinoma (HCC) is the third most frequent cause of tumor-related death in western countries. The so called curative therapies are effective only in the minority of the patients, so drug-based therapies remain the ultimate goal for the treatment of this disease. Recent preclinical data indicate that Transforming growth factor beta 1 (TGF-b1) is an important pharmacological target in HCC treatment. We recently demonstrated that inhibition of the TGF-b1 pathway by LY2109761 decreases the tumor burden, angiogenesis and metastatic dissemination in HCC. Here, we show that loading LY2109761 into polyelectrolyte microcapsules improves the uptake of this drug in HCC cells. This improvement was measured by both confocal laser scanning microscopy and fluorimetric analysis. Firstly, we fabricated hollow polyelectrolyte capsules by coating colloidal templates through a layer by-layer technique. Secondly, we improved the microcapsules wall stability by chemical cross-linking in order to facilitate the gradual release of LY2109761 into the cells. Notably, we found that cross-linked biodegradable capsules show no cytotoxicity as evaluated by the cell viability MTT assay. Finally, we observed that LY2109761- loaded biodegradable capsules were able to more effectively inhibit tumor cell migration than LY2109761 alone, indicating that LY2109761-loaded capsules may enhance TGF-b1 pathway inhibition treatment. This strategy represents a novel avenue of investigation into the development of new nanotechnology-based tools to combat hepatocarcinoma.