Abstract 2070: Gemcitabine-loaded microparticles promote cancer cell death in subcutaneous pancreatic cancer xenografts
Authors: Munoz-Sagastibelza Maria , Kurbatov Vadim , Dynes Sophia , Caceres Jennifer , Chen Michael , Gupta Raavi , Burkhart Catherine , Martello-Rooney Laura 
Published: July 2016

Pancreatic cancer is the fourth leading cause of cancer death in the United States with only 7% of diagnosed patients surviving 5 years. Most pancreatic cancer patients are not surgical candidates due to advanced stage at diagnosis. Current systemic chemotherapies, while exposing patients to the adverse side effects of treatment, have not been very effective at decreasing tumor burden primarily due to poor systemic drug uptake resulting from the dense stromal nature of pancreatic tumors. Poly(lactic-co-glycolic acid)-based (PLGA) microparticles (MPs) are a promising tool for localized drug delivery within the tumor due to their high biocompatibility, flexibility in the encapsulation of different drugs and extended drug release inside the tumor. The present study investigated whether gemcitabine-loaded microparticles (GMPs) in the range of 10-50 microns, in comparison with blank (no drug) MPs (BMPs), saline intraperitoneal injection (SIP) and gemcitabine intraperitoneal injection (GIP) as controls, are able to promote cancer cell killing effects in vivo.

In vitro studies with PANC-1 and MIAPaCa-2 human pancreatic adenocarcinoma cell lines treated with different PLGA co-polymer ratios used to encapsulate gemcitabine showed enhanced cell killing and decreased colony formation in the longer release co-polymer ratio after 2 weeks of treatment. Subsequently, the in vivo efficacy of GMPs was tested by direct injection of GMPs into established subcutaneous MIAPaCa-2 tumors in nude mice. Treatment commenced when tumor volume was approximately 250 mm3. Following two weeks of treatment, there was a trending decrease in tumor volume in the GMPs-injected MIAPaCa-2 tumors compared to the BMPs-injected tumors. When comparing the SIP to GIP groups, there was no difference in final tumor volume emphasizing the lack of effective penetration of systemic gemcitabine into the tumor. In addition, we observed less tumor progression in the GMPs group compared to the others. At the endpoint, the tumors were excised, frozen in OCT compound and sectioned to visualize fluorescent MPs and to detect apoptosis by immunofluorescence. Interestingly, we observed a significant increase in apoptosis in the tumors treated with GMPs compared to the BMP tumors (p&lt;0.05) as well as the SIP (p&lt;0.05) and GIP tumors (p&lt;0.05).

In conclusion, our data suggest that gemcitabine-loaded MPs could decrease tumor volume and increase local pancreatic tumor cell death. Further studies are needed to optimize the MPs loading and injection to confirm its efficacy. The described drug delivery method has the potential to be a more efficient local treatment modality than systemic gemcitabine against pancreatic cancer.

Citation Format: Maria Munoz-Sagastibelza, Vadim Kurbatov, Sophia Dynes, Jennifer Caceres, Michael Chen, Raavi Gupta, Catherine Burkhart, Laura Martello-Rooney. Gemcitabine-loaded microparticles promote cancer cell death in subcutaneous pancreatic cancer xenografts. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2070.