Development of a thermosensitive hydrogel system for local delivery of radionuclide and chemotherapeutic drug in a hepatocellular carcinoma

Objectives This study evaluated drug delivery system for local cancer radiotherapy combinated chemotherapy using a thermosensitive hydrogel consisting of therapeutic radionuclide and chemotherapeutic drugs.

Methods A thermally sensitive copolymer (PCL-PEG-PCL) was designed to spontaneously undergo a soluble-insoluble phase transition between room temperature and body temperature upon intratumoral injection. 188Re-Tin colloid and liposomal doxorubicin (Lipo-Dox®) were loaded into hydrogel, a scanning electron microscope was used to observe morphology of dual loaded hydrgel. After intratumoral administration of 188Re-colloid loaded hydrogel into mouse hepatocellular carcinoma (HCC), their retention within the tumor, spatio-temporal distribution, and therapeutic effect were evaluated and quantified.

Results The releasing curve of radionuclide and doxorubicin from hydrogel shows a slowly stable and linear trend within 10 days. The residence time of the 188Re-Tin colloid loaded hydrogel in the tumor was significantly longer than the Re-188 perrhenate (ReO4). The thermal transition of hydrogel significantly held the radionuclide in the tumor, whereas free 188Re perrhenate (ReO4) was quickly eliminated from the tumor. In the study on therapeutic efficacy, the tumor-bearing mice treated with bimodality radiochemotherapeutics of 188Re-Tin colloid and liposomal doxorubicin (Lipo-Dox®) co-loaded hydrogel showed better tumor growth inhibition than those treated with radiotherapeutics of 188Re- colloid loaded hydrogel and liposomal doxorubicin loaded hydrogel. 188Re-Tin colloid and liposomal doxorubicin (Lipo-Dox®) co-loaded hydrogel synergistically inhibited tumor growth, resulting in up to 70% complete regression of well-established tumors on day 30.

Conclusions Therefore, this injectable and biodegradable hydrogel has the potential to offer dual therapies for the synergistic combination of radiotherapy and chemotherapy in the treatment of hepatocellular carcinoma