Abstract 1895: Characterization of gemcitabine- and paclitaxel-loaded poly(lactic-co-glycolic acid) microparticles as a treatment for pancreatic ductal adenocarcinoma using in vitro models

Abstract

This study aims to characterize the in vitro efficacy of gemcitabine- and paclitaxel-loaded poly(lactic-co-glycolic acid) microparticles as a treatment modality for pancreatic ductal adenocarcinoma (PDAC). The goal is the development of the drug-loaded microparticles (MPs) for direct intratumoral injection as a treatment option for patients with borderline resectable or locally advanced tumors. Because the MPs are injected directly into the tumor, a higher dose of the chemotherapeutic should reach the cancer cells and minimal, if any, should enter the patient’s systemic circulation, which would increase efficacy and decrease systemic toxicity compared to systemic drug infusions. Methods: Gemcitabine-loaded MPs (GMPs), paclitaxel-loaded MPs (PMPs), and blank (no drug) MPs (BMPs) were formulated using a water in oil in water (W/O/W) emulsion. The human PDAC cell lines MIA PaCa-2 and PANC-1 were treated with GMPs and PMPs alone, or in combination, for three or six days with BMPs used as the control. After the treatment course, MTS cell viability assays were performed to assess the cytotoxicity of the different treatments, or cells were collected for flow cytometry to analyze apoptosis and cell cycle phase. Cells were also treated with free gemcitabine and paclitaxel to determine the IC50 and compare cytotoxicity to the MPs treatments via cell viability assays and flow cytometry. Additionally, patient derived PDAC organoids were treated with GMPs and PMPs alone, or in combination, for five days with BMPs as the control. After five days, organoid viability was assessed via CellTiter-Glo enabling comparison with free drug treatments. Results: Treatment with the different MPs regimens results in significant cell death in both cell lines and organoids as compared to the controls. MIA PaCa-2 cells were more sensitive to free gemcitabine and GMPs treatment than PANC-1 cells. However, both cell lines were similarly sensitive to free paclitaxel and PMPs treatment, with PANC-1 cells displaying more sensitivity to paclitaxel-based treatments than gemcitabine-based treatments. The combination MPs treatment performed similarly to the GMPs treatment in both cell lines. The treated organoid lines did not have statistically significant differences in their sensitivities to the different MPs treatments. Conclusion and Future Directions: Using in vitro assays, we assessed the effects of the drug-loaded MP treatments on the viability of PDAC cell lines and patient derived organoids. Next steps will involve cell cycle and apoptosis analysis utilizing flow cytometry of the two cell lines after exposure to the MPs treatments. Additionally, the sensitivity of the organoids to MPs treatments will be compared to free drug treatments to assess the efficacy of MPs therapy over traditional therapy. Citation Format: Stanley Soroka, Dennis Plenker, Hardik Patel, Amber Habowski, David Tuveson, Laura Martello-Rooney. Characterization of gemcitabine- and paclitaxel-loaded poly(lactic-co-glycolic acid) microparticles as a treatment for pancreatic ductal adenocarcinoma using in vitro models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1895.