NERDG 2026
Poster 34 Abstract
A First-in-Class Perfluorocarbon-Loaded Solid Lipid Nanoparticles for Oxygen Delivery
Shekh Md Newaj, Lynn Akwa, Amit Chandra Das, Paromita Paul Pinky, Jelena M. Janjic
Duquesne University
Presenting Author: Shekh Md Newaj
Corresponding Author: Jelena M. Janjic, [email protected]
Purpose
The absence of a clinically approved artificial oxygen carrier (AOC) in current organ preservation systems leaves donor organs vulnerable to ischemia–reperfusion injury (IRI) and contributes to delayed graft function after transplantation. Hemoglobin-based oxygen carriers (HBOCs) and red blood cells (RBCs) substitutes have failed to gain broad regulatory approval due to safety concerns, including an increased risk of myocardial infarction. In contrast, perfluorocarbon (PFC)-based nanocarriers have shown high oxygen-carrying capacity and chemical and biological inertness. Previously, we developed Quality-by-Design-driven PFC nanoemulsion for optimized oxygen loading/offloading kinetics. Here, we focus on the development of a perfluorocarbon-loaded solid lipid-nanoparticle (PL-SLN) oxygen carrier, designed to be easily incorporated into a clinically approved perfusate under varied machine perfusion conditions.
Methods
During pre-formulation phase, composition and process parameters were screened to identify critical material attributes (CMA) and critical process parameters (CPP). A Quality-by-Design (QbD) approach was employed to optimize the PL-SLN formulation using a 17-run, 3-level, 6-factor Definitive Screening Design with multiple linear regression (MLR) modeling to identify significant parameters. Biocompatibility was evaluated using an in vitro cell viability assay in RAW 264.7 macrophages, and an oxygen bubbling test was conducted to characterize the PL-SLN’s oxygen carrying capacity.
Results
Pre-formulation studies identified solid lipid and PFC content as CMA whereas cooling strategy and storage temperature were detected as CPP. MLR modeling revealed that reduced homogenization time significantly increased perfluorocarbon loading (p < 0.05), consistent with previously reported increases in oxygen-carrying capacity (Lambert & Janjic, 2021). Based on model predictions, the optimized formulation (Run 12) was successfully scaled up to threefold (100 g to 300 g), maintaining >80% PFC loading and <10% particle size change across stress tests. Integration of microfluidization significantly reduced particle size and improved cell viability. PL-SLNs showed high oxygen loading in the oxygenation test.
Conclusion
We have therefore successfully developed stable, biocompatible PL-SLNs with high oxygen-carrying capacity suitable for organ preservation. The observed size-dependent cell viability and PFC sedimentation highlight the importance of microfluidization as a key process parameter. Further optimization will focus on increasing PFC loading, assessing the lipid shell impact on oxygen delivery, and developing a lyophilized PL-SLN formulation to support large-scale studies.
Keywords
Perfluorocarbon, QbD, Solid lipid nanoparticles, Artificial Oxygen Carrier, Microfluidization
Poster 34 Abstract
A First-in-Class Perfluorocarbon-Loaded Solid Lipid Nanoparticles for Oxygen Delivery
Shekh Md Newaj, Lynn Akwa, Amit Chandra Das, Paromita Paul Pinky, Jelena M. Janjic
Duquesne University
Presenting Author: Shekh Md Newaj
Corresponding Author: Jelena M. Janjic, [email protected]
Purpose
The absence of a clinically approved artificial oxygen carrier (AOC) in current organ preservation systems leaves donor organs vulnerable to ischemia–reperfusion injury (IRI) and contributes to delayed graft function after transplantation. Hemoglobin-based oxygen carriers (HBOCs) and red blood cells (RBCs) substitutes have failed to gain broad regulatory approval due to safety concerns, including an increased risk of myocardial infarction. In contrast, perfluorocarbon (PFC)-based nanocarriers have shown high oxygen-carrying capacity and chemical and biological inertness. Previously, we developed Quality-by-Design-driven PFC nanoemulsion for optimized oxygen loading/offloading kinetics. Here, we focus on the development of a perfluorocarbon-loaded solid lipid-nanoparticle (PL-SLN) oxygen carrier, designed to be easily incorporated into a clinically approved perfusate under varied machine perfusion conditions.
Methods
During pre-formulation phase, composition and process parameters were screened to identify critical material attributes (CMA) and critical process parameters (CPP). A Quality-by-Design (QbD) approach was employed to optimize the PL-SLN formulation using a 17-run, 3-level, 6-factor Definitive Screening Design with multiple linear regression (MLR) modeling to identify significant parameters. Biocompatibility was evaluated using an in vitro cell viability assay in RAW 264.7 macrophages, and an oxygen bubbling test was conducted to characterize the PL-SLN’s oxygen carrying capacity.
Results
Pre-formulation studies identified solid lipid and PFC content as CMA whereas cooling strategy and storage temperature were detected as CPP. MLR modeling revealed that reduced homogenization time significantly increased perfluorocarbon loading (p < 0.05), consistent with previously reported increases in oxygen-carrying capacity (Lambert & Janjic, 2021). Based on model predictions, the optimized formulation (Run 12) was successfully scaled up to threefold (100 g to 300 g), maintaining >80% PFC loading and <10% particle size change across stress tests. Integration of microfluidization significantly reduced particle size and improved cell viability. PL-SLNs showed high oxygen loading in the oxygenation test.
Conclusion
We have therefore successfully developed stable, biocompatible PL-SLNs with high oxygen-carrying capacity suitable for organ preservation. The observed size-dependent cell viability and PFC sedimentation highlight the importance of microfluidization as a key process parameter. Further optimization will focus on increasing PFC loading, assessing the lipid shell impact on oxygen delivery, and developing a lyophilized PL-SLN formulation to support large-scale studies.
Keywords
Perfluorocarbon, QbD, Solid lipid nanoparticles, Artificial Oxygen Carrier, Microfluidization
