Intra-arterial Therapy Using Micellar Nanoparticles Incorporating SN-38 in a Rat Pancreatic Tumor Model

Abstract

Purpose To evaluate advantages of micellar nanoparticles encapsulating SN-38, a biologically active metabolite of irinotecan, in intraarterial therapy for pancreatic cancer. Materials and Methods Rat pancreatic cancer cells (DSL-6A/C1) were implanted in Lewis rats under laparotomy. This study consists of two parts. Firstly, after confirming tumor formation by ultrasonography, celiac arteriography was performed, and tumor blood supply was visually evaluated by dye injection and CT during arteriography. Secondly, 18 rats were divided into two groups; the Micellar Nanoparticles group and the Irinotecan Infusion group. Micellar nanoparticles or irinotecan was injected via the celiac artery, and SN-38 and irinotecan concentrations in the tumor, duodenum and pancreatic parenchyma, were measured at 5 min, 6 h and 24 h. Results The maximum concentration (Cmax) of SN-38 were shown at 6 h in the Micellar Nanoparticles group, while Cmax of irinotecan was shown at 5 min in the Irinotecan Infusion group. Tumor concentration in the Micellar Nanoparticles group maintained elevated for 24 h without significant decrease (P = 0.068). Conversely, a significant decrease was observed in the regular pancreas parenchyma (P = 0.006) and duodenum (P = 0.028). In the Irinotecan Infusion group, tumor irinotecan concentration significantly decreased at 24 h (P = 0.016). Conclusion Micellar nanoparticles may improve arterial infusion chemotherapy for pancreatic cancer. These nanoparticles have the potential to reduce SN-38 accumulation in duodenum, while increasing it in the tumor. Further research is warranted to validate and expand upon these findings.