NERDG 2026
Poster 35 Abstract
Scalable Perfluorocarbon Nanoemulsions for Oxygen and Resveratrol Delivery to Prevent Ischemia-Reperfusion Injury During Organ Preservation
Smith Patel, Paromita Paul Pinky, Amit Chandra Das, Caitlin Crelli, Anneliese Troidle, Eric Lambert, Rebecca McCallin, Vidya Surti, Jelena M. Janjic
School of Pharmacy, Graduate School of Pharmaceutical Sciences, Duquesne University, 600 Forbes Ave., Pittsburgh, PA 15282, USA
Presenting Author: Smith Patel
Corresponding Author: Jelena M. Janjic, [email protected]
Purpose
Ischemia–reperfusion injury (IRI) is a major barrier to successful solid organ transplantation. Ischemia induces anaerobic metabolism and mitochondrial dysfunction, while reperfusion triggers a surge of reactive oxygen species (ROS) and lipid peroxidation. These hallmarks reflect ferroptosis, an iron-dependent form of regulated cell death that drives oxidative damage during reperfusion. Resveratrol (RSV) can mitigate IRI by inhibiting ferroptosis through ROS scavenging and upregulating antioxidant enzymes; however, its poor solubility and rapid clearance limit its clinical utility. To address these challenges, we developed a first scalable dual-function perfluorocarbon nanoemulsion (PFC-NE) perfusate capable of delivering oxygen and resveratrol (RSV), while enabling near-infrared fluorescence (NIRF) imaging of perfusate distribution during organ preservation.
Methods
A Quality-by-Design (QbD) framework guided the development of drug-free (DF) and resveratrol-loaded nanoemulsions (NEs) at scales of 250–1000 mL using microfluidization. Colloidal and fluorescence attributes, RSV loading, and release were characterized using DLS, NIRF imaging, and HPLC. Oxygen saturation was assessed using a membrane oxygenator and oxygen bubbling. Antioxidant activity of RSV-NE was measured using the oxygen radical scavenging antioxidant capacity (ORAC) assay, while cytotoxicity and ferroptosis inhibition were evaluated in RAW 264.7 macrophages.
Results
All PFC-NE batches demonstrated consistent droplet size (90–110 nm), low PDI (<0.3), and >80% PFC loading across scales, confirming high reproducibility. DF-NE and RSV-NE maintained colloidal and fluorescence stability following centrifugation, filtration, serum exposure, oxygenation, and 3-month storage. RSV-NE showed high drug loading and sustained release (63.37 ± 2.48% at day 5) compared with rapid release from free drug solution, ensuring drug availability over clinically relevant 24–48 h organ preservation durations. PFC-NE exhibited higher and more stable oxygen saturation than the University of Wisconsin solution for 6 h. RSV-NE demonstrated concentration-dependent radical scavenging and exhibited reduced cytotoxicity, thereby preventing RSL3-induced ferroptosis in RAW 264.7 murine macrophages compared to the free drug.
Conclusion
This study establishes a robust and scalable PFC-NE platform integrating RSV and oxygen delivery, along with NIRF-based non-invasive live monitoring of organ perfusion during machine-supported preservation. These combined features position PFC-NE as a promising next-generation acellular perfusate for preventing IRI and improving graft viability during ex vivo machine perfusion.
Keywords
nanoemulsion; oxygen delivery; resveratrol; ferroptosis; ischemia reperfusion injury (IRI); organ preservation; machine perfusion
Poster 35 Abstract
Scalable Perfluorocarbon Nanoemulsions for Oxygen and Resveratrol Delivery to Prevent Ischemia-Reperfusion Injury During Organ Preservation
Smith Patel, Paromita Paul Pinky, Amit Chandra Das, Caitlin Crelli, Anneliese Troidle, Eric Lambert, Rebecca McCallin, Vidya Surti, Jelena M. Janjic
School of Pharmacy, Graduate School of Pharmaceutical Sciences, Duquesne University, 600 Forbes Ave., Pittsburgh, PA 15282, USA
Presenting Author: Smith Patel
Corresponding Author: Jelena M. Janjic, [email protected]
Purpose
Ischemia–reperfusion injury (IRI) is a major barrier to successful solid organ transplantation. Ischemia induces anaerobic metabolism and mitochondrial dysfunction, while reperfusion triggers a surge of reactive oxygen species (ROS) and lipid peroxidation. These hallmarks reflect ferroptosis, an iron-dependent form of regulated cell death that drives oxidative damage during reperfusion. Resveratrol (RSV) can mitigate IRI by inhibiting ferroptosis through ROS scavenging and upregulating antioxidant enzymes; however, its poor solubility and rapid clearance limit its clinical utility. To address these challenges, we developed a first scalable dual-function perfluorocarbon nanoemulsion (PFC-NE) perfusate capable of delivering oxygen and resveratrol (RSV), while enabling near-infrared fluorescence (NIRF) imaging of perfusate distribution during organ preservation.
Methods
A Quality-by-Design (QbD) framework guided the development of drug-free (DF) and resveratrol-loaded nanoemulsions (NEs) at scales of 250–1000 mL using microfluidization. Colloidal and fluorescence attributes, RSV loading, and release were characterized using DLS, NIRF imaging, and HPLC. Oxygen saturation was assessed using a membrane oxygenator and oxygen bubbling. Antioxidant activity of RSV-NE was measured using the oxygen radical scavenging antioxidant capacity (ORAC) assay, while cytotoxicity and ferroptosis inhibition were evaluated in RAW 264.7 macrophages.
Results
All PFC-NE batches demonstrated consistent droplet size (90–110 nm), low PDI (<0.3), and >80% PFC loading across scales, confirming high reproducibility. DF-NE and RSV-NE maintained colloidal and fluorescence stability following centrifugation, filtration, serum exposure, oxygenation, and 3-month storage. RSV-NE showed high drug loading and sustained release (63.37 ± 2.48% at day 5) compared with rapid release from free drug solution, ensuring drug availability over clinically relevant 24–48 h organ preservation durations. PFC-NE exhibited higher and more stable oxygen saturation than the University of Wisconsin solution for 6 h. RSV-NE demonstrated concentration-dependent radical scavenging and exhibited reduced cytotoxicity, thereby preventing RSL3-induced ferroptosis in RAW 264.7 murine macrophages compared to the free drug.
Conclusion
This study establishes a robust and scalable PFC-NE platform integrating RSV and oxygen delivery, along with NIRF-based non-invasive live monitoring of organ perfusion during machine-supported preservation. These combined features position PFC-NE as a promising next-generation acellular perfusate for preventing IRI and improving graft viability during ex vivo machine perfusion.
Keywords
nanoemulsion; oxygen delivery; resveratrol; ferroptosis; ischemia reperfusion injury (IRI); organ preservation; machine perfusion
