Abstract B25: Drug-eluting microparticles for the treatment of pancreatic cancer: Preliminary in vivo results.

Pancreatic cancer is the fourth leading cause of cancer death in the U.S. Current treatment regimens have had a minimal impact on altering the course of the disease, establishing the need for alternative modalities of therapy. One of the main issues with systemic chemotherapy is in vivo data demonstrating compromised blood flow to the pancreatic tumor offering one explanation for the lack of efficacy in pancreatic cancer patients. A novel option would be to deliver drug directly to the pancreatic tumor over a sustained period of time to circumvent this barrier, and at the same time decrease the side effects associated with systemic delivery. Here we explore the feasibility of direct injection of biodegradable polymer-based microparticles (MPs) with an approximate size of 10 μm into the tail portion of the mouse pancreas. A laparotomy was performed on C57BL/6 mice to expose the pancreas followed by injection of 50 μl phosphate-buffered saline (PBS), 50 μl blank MPs/PBS or 25 μl blank MPs/PBS into the pancreatic tail using a 29-gauge needle (165 μm inner diameter). The mice were sacrificed at the following post-operative timepoints: 24 hrs, 3 days and 7 days. The mice were weighed daily and blood was drawn pre- and post-operatively for pancreatic enzyme testing. Mouse tissue samples of the pancreas, liver, spleen and duodenum were placed in formalin upon sacrifice. All of the mice survived the surgery and exhibited minimal weight loss, which was reversed by day 7. Lipase and amylase levels were mildly elevated after 24 hrs, but returned to pre-bleed levels by day 3. The analysis of the pancreatic tissue sections disclosed acinar cell damage only in the area surrounding the injection site and MP deposit. There was no evidence of pancreatitis, a concern following manipulation of the pancreas. No indication of MP migration was observed in sections of the liver, spleen or duodenum. These findings established that direct injection of MPs into the mouse pancreas was feasible and safe and supported proceeding to the next phase of utilizing drug-loaded MPs in a mouse model of pancreatic cancer. An orthotopic nude mouse model of pancreatic cancer was employed by injecting PANC-1 human pancreatic cancer cells into the tail section of the mouse pancreas via laparotomy. Two weeks post-cancer cell injection, a second laparotomy was performed to inject 50 μl drug-loaded MPs (average size range 25-50 μm) or 50 μl PBS into the same tail section of the pancreas. The mice were weighed 3 times weekly and blood was drawn pre- and postoperatively to measure pancreatic enzyme levels. For HPLC detection of drug concentration, mouse plasma and tissue samples were collected from control and treated mice at 4 weeks post-MP injection. Mouse tissue samples also were taken to evaluate the local effects of constant drug release on the pancreatic tumors and to determine the extent of drug delivery to the spleen and liver. Positive results of these combined studies will justify additional preclinical investigation in a transgenic mouse model of pancreatic cancer, with the final objective to validate the potential use of drug-eluting MPs to deliver localized tumor treatment for patients with pancreatic cancer. Citation Format: Amon Asgharpour, Manoj Ganesh, Jing Ling, Albert Stanek, Wenchun Xie, Alicia Gooding, Sherif Andrawes, Richard Gross, Frank Gress, Laura Martello-Rooney. Drug-eluting microparticles for the treatment of pancreatic cancer: Preliminary in vivo results. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Progress and Challenges; Jun 18-21, 2012; Lake Tahoe, NV. Philadelphia (PA): AACR; Cancer Res 2012;72(12 Suppl):Abstract nr B25.