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CC BY-NC-ND 4.0 · Endosc Int Open 2019; 07(08): E1008-E1017
DOI: 10.1055/a-0953-2070
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Owner and Copyright © Georg Thieme Verlag KG 2019

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

Jennifer Caceres‡   *
1   Medicine Digestive and Liver Diseases, Columbia University Medical Center, New York, New York, United States
,
Maria Munoz-Sagastibelza‡   *
2   SUNY Downstate Medical Center, Department of Medicine, Division of Gastroenterology & Hepatology, Brooklyn, New York, United States
,
A. K. M. Nawshad Hossian
3   University of Louisiana at Monroe, College of Pharmacy, Monroe, Louisiana, United States
,
Jenny Paredes
2   SUNY Downstate Medical Center, Department of Medicine, Division of Gastroenterology & Hepatology, Brooklyn, New York, United States
,
Kaylene Barrera
4   SUNY Downstate Medical Center, Department of Surgery, Brooklyn, New York, United States
,
George Mattheolabakis
3   University of Louisiana at Monroe, College of Pharmacy, Monroe, Louisiana, United States
,
Laura A. Martello
2   SUNY Downstate Medical Center, Department of Medicine, Division of Gastroenterology & Hepatology, Brooklyn, New York, United States
,
Shivakumar Vignesh
2   SUNY Downstate Medical Center, Department of Medicine, Division of Gastroenterology & Hepatology, Brooklyn, New York, United States
› Author Affiliations
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Publication History

Publication Date:
08 August 2019 (online)

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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.

* Drs. Caceres and Munoz-Sagastibelza: These authors contributed equally.


 

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