Published in:
01-08-2017 | Laboratory Investigation
New Interventional Treatment Model for Pancreatic Neoplasms Using Gemcitabine-Eluting Hydrogel Devices: In Vitro and In Vivo Results
Published in: CardioVascular and Interventional Radiology | Issue 8/2017
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Objectives
In vitro and in vivo evaluation of fast- and slow-release gemcitabine-eluting hydrogel (GEH) devices.
Methods
For in vitro elution, the GEH devices were placed in phosphate-buffered saline at 37 °C. Periodically, the solution was analyzed for gemcitabine. The devices consisting of fast release (n = 8), slow release (n = 6), or bland (n = 4) were delivered through a 5-Fr catheter into the gastroduodenal artery of a pig. Additionally, four pigs were treated with intravenous (IV) injection of gemcitabine. Pigs were killed at day 1 (n = 9), day 7 (n = 11), or day 21 (n = 2). Gemcitabine concentrations in the plasma and tissues were determined.
Results
In vitro, gemcitabine was completely eluted within 6 h or 30 days for the fast- and slow-release devices, respectively. All 22 pigs were treated without morbidity or mortality. Gemcitabine plasma concentrations peaked at about 105,000 ± 30,000, 252 ± 101, 22 ± 29, and 0 ± 0 ppb for the IV, fast-release, slow-release, and bland treatments, respectively. At days 1 and 7, gemcitabine concentrations were higher in the pancreas for the GEH devices than IV. Gemcitabine delivery to the pancreas was sustained over 21 days in the slow-release group.
Conclusions
Treatment with GEH devices resulted in at least equivalent gemcitabine concentration in the pancreas and reduced concentration in the plasma, heart, liver, and duodenum, at least equivalent to IV injection and reduced concentrations elsewhere. These results show the potential of sustained local delivery of gemcitabine to treat pancreatic neoplasms with reduced side effects.