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

Abstract

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 injectable therapy for pancreatic cancer: A systematic review

“…Successful local delivery of chemotherapeutics is a logical option given their proven safety profile with systemic therapy. Some of these agents have been delivered into normal pancreatic tissue in animal studies using EUS-FNI with no significant AEs[ 43 , 44 ] Results of the clinical study using EUS-guided gemcitabine injections are encouraging although additional data is required to confirm these findings with regulated delivery of standard multimodality therapy and controlled trials assessing the effect of multiple sessions and escalating doses towards significant clinical advantage. In theory, immunotherapy is an attractive option, but various challenges with PDAC include the immune-suppressive TME including stromal cellular and molecular components, and other multiple immunological barriers making PDAC a “cold” tumor.…”

Endoscopic ultrasound guided interventions in the management of pancreatic cancer

“…A feasibility study using EUS-guided injection of gemcitabine in 38 patients with locally advanced and metastatic pancreatic cancer confirmed the safety and efficacy of the technique. More recently, a feasibility study of EUS guided injection of a novel polymer-based microparticles for a drug delivery system in a pig model appeared promising[ 53 ]. A phase I study evaluating the role of EUS guided injection of epidermal growth factor receptor antibody cetuximab as a radiosensitizer with chemoradiation for locally advanced pancreatic cancer in 16 patients proved its feasibility and safety profile when administered with abdominal radiation and concurrent gemcitabine.…”