Evaluation of the feasibility of intrapancreatic delivery of drug-loaded microparticles via EUS-guided fine needle injection using a swine model

Background and study aims Patients with pancreatic cancer often have locally advanced or metastatic disease and are not candidates for curative surgery. Polymer-based microparticles (MPs) represent a drug delivery system that offers sustained release of a chemotherapeutic drug after intralesional injection for local tumor management. The aim of this study was to determine the feasibility of endoscopic ultrasound-guided fine-needle injection (EUS-FNI) of drug-loaded MPs tagged with a fluorophore and fiducial markers for locating the injection site. Secondary aims were to determine the tissue-specific effects of MPs. Methods Five pigs underwent EUS with selection of an injection site within the pancreas that was marked by placing fiducial markers prior to the MPs injection. EUS-FNI of either blank microparticles (BMPs), containing no drug, or gemcitabine-loaded microparticles (GMPs) was performed. A saline flush containing Spot Endoscopic Marker was used to expel any residual MPs in the needle shaft and tattoo the injection site. Results A green fluorescent protein flashlight was used to successfully identify the site of MP injection sites in the dissected pancreas. Frozen sections of pig pancreas demonstrated a defined deposit, confirming the delivery of the MPs. Finally, fluorescence microscopy showed activation of caspase-mediated cell death in pancreases of animals that received injections of GMPs. Conclusions This pilot study demonstrated that fiducial marker placement and pancreatic EUS-FNI of MPs was successful in all pigs with no animals demonstrating pancreatitis. Further studies are needed to determine the role for intralesional injection of drug-loaded MPs in borderline resectable or unresectable pancreatic cancer.

Endoscopic ultrasound guided injection of iron oxide magnetic nanoparticles for liver and pancreas: a feasibility study in pigs.

Aims: Pancreatic cancer and hepatocellular carcinoma are two of the most aggressive types of cancer with limited therapeutic options in stages of advanced disease. Our objective is to assess the safety and feasibility of injecting iron oxide nanoparticles (IONs) via endoscopic ultrasound (EUS)-guidance, both systemically and locally in the liver and pancreas in order to study new potential therapies for liver and pancreatic tumors. Material and methods: Six domestic pigs were used for our study design, and divided into three groups: two were injected in the portal vein, and other four were subjected to local exposure of IONs in the liver and pancreas, two each. The pigs were on a 7 days follow-up and necropsy was performed with their organs harvested. A 3T MRI scan was also performed. Results: All animals underwent an endoscopic ultrasound fine needle injection (EUS-FNI) procedure without any complications. EUS-FNI procedure had an average time of 5 minutes and 21 seconds and consisted of 2 ml of ION injection. No perforations and no risk of potential bleeding were recorded. Macroscopic changes were observed only after pancreatic EUS-FNI. A significant amount of IONs was observed in the liver after local injection and after vascular EUS-FNI. The imaging results were confirmed by pathological examination with most of the IONs accumulated in Ito-like cells, Kupfer cells, and sinusoids. Conclusions: IONs have been widely studied for both diagnostic and therapeutic purposes. Their injection through EUS-guidance may develop new diagnosis strategies as well as curative or palliative therapies in pancreatic and liver tumors.