A novel long-sustaining system of apatinib for long-term inhibition of the proliferation of hepatocellular carcinoma cells

Background: Apatinib is a newly approved antitumor drug (molecular targeted agent/small molecular kinase inhibitor) for advanced hepatocellular carcinoma (HCC) treatment. However, current oral administration of apatinib could induce the even distribution of drugs in the body and cause the concentration of apatinib in the HCC location to be limited or insufficient. Therefore, it is urgent to develop novel formulations of apatinib to improve its efficiency. Materials and methods: Apatinib was prepared to form a stable and even dispersion with cyclodextrin (a clathrate complex/inclusion complex named Apa-Cyc). A temperature-sensitive phase-change hydrogel of apatinib (named Apa-Gel) was prepared using apatinib-cyclodextrin and poloxamer 407. Apa-Gel was injected into HCC tissues in nude mice to examine the long-term antitumor effect. Results: Apa-Gel can transform from liquid to hydrogel at near body temperature and maintain slow release of apatinib in HCC tumor tissues. When injected subcutaneously, one-time administration of Apa-Gel has a long-acting antitumor effect on the subcutaneous growth or epithelial-mesenchymal transition process of HCC cells. Conclusion: This novel slow-releasing system allows apatinib to be released effectively on the long term and facilitates tissue attachment, thereby preserving the efficiency of apatinib over the long term.