Abstract No. 335 - Transcatheter delivery of sorafenib-eluting polylactide-co-glycolide microspheres: therapy response studies in a rat model of hepatocellular carcinoma

Abstract

Purpose Sorafenib is an effective palliative treatment against hepatocellular carcinoma (HCC), however the oral tablet formulation is associated with severe side effects and low serum levels suggest delivery of insufficient doses. A drug-eluting bead formulation for catheter-directed delivery should increase tumor doses and decrease side effects. Thus, polylactide-co-glycolide (PLG) microspheres were developed to encapsulate sorafenib and an iron oxide ferrofluid to allow for MRI monitored delivery. The purpose of this study was to show in vivo therapy response in a rat HCC model after microsphere delivery Materials and Methods McA-RH7777 rat HCC cells were implanted in the livers of 18 Sprague Dawley rats. Of the 18 rats, 6 rats were given sorafenib-eluting PLG microspheres, 6 rats were given sham controls of unloaded PLG microspheres and 6 rats were left as untreated controls. After 1 week, microsphere-infused rats underwent invasive catheterization (24 g catheter) of the proper hepatic artery before infusion of 4 mg of spheres. MRI was performed pre and post-infusion using T2-weighted sequences and a 7T MRI scanner (Bruker Clinscan, Billerica, MA, USA). The rats were sacrificed 72 h post-treatment and angiogenesis was assessed via rat anti-CD34 immunohistochemistry for microvessel density (MVD). Rat anti-CD34 slides were imaged with a TissueFaxs microscope (TissueGnostics GmbH, Vienna, Austria) and MVD was expressed as percent areas of positive staining in the tumor as measured by TissueGnostics’ Histoquest program. Results The MVDs were 4.10±0.69, 4.41±1.42 and 2.86±1.82 (mean±SD) for untreated, sham control and sorafenib-eluting PLG microsphere treated groups, respectively, thus indicating therapy response with the sorafenib-eluting PLG microspheres. Unpaired Student’s T-test and one-way ANOVA (Scheffe post-hoc correction) statistical analysis confirmed statistical significance (p Conclusion Sorafenib-eluting PLG microspheres induced tumor MVD reductions in vivo in a Sprague Dawley HCC model. This platform has potential to improve therapeutic efficacy and reduce toxicity via catheter-directed delivery to HCC tumors.