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Development of Lipid Nanoparticles Based Drug Delivery Systems Targeting Oxidative Stress for Disease Prevention and Therapy - Preeclampsia to Acute Lung Injury

Rashi Porwal, University of Nebraska - Lincoln


This thesis delves into innovative approaches to designing lipid nanoparticle-based drug delivery systems using in vitro cell culture models that mimic the cellular microenvironment under disease conditions. The research specifically focuses on pathologies associated with oxidative stress, such as preeclampsia and acute lung injury. The study aims to understand the molecular mechanisms altered during these pathological conditions and develop tailored lipid nanoparticles to address these unique circumstances. We initially examined preeclampsia (PE), a life-threatening pregnancy complication with no effective treatments that often result in preterm labor induction. Our transcriptomic analysis of clinical samples from preeclamptic women revealed notable alterations in stiffness-related markers, extracellular matrix functions, and mitochondrial activity. Based on these findings, we developed a novel BEASTS (Bioengineered Adhesive Siloxane-based Tunable Stiffness) in vitro platform to investigate stiffness-driven placental dysfunction and its molecular underpinnings in both healthy and preeclamptic conditions. When altering stiffness, we observed significant changes in critical cellular functions that closely resembled clinical findings, suggesting that this model could facilitate the understanding of PE's molecular mechanisms and aid in developing potential therapeutics. Additionally, we investigated Acute Lung Injury, a critical condition in which elevated oxidative stress impairs the therapeutic capacity of mesenchymal stem cells (MSCs). To tackle this challenge, we designed hyaluronic acidcoated lipid nanoparticles loaded with vitamin E. In vitro and in vivo studies showed that these vitamin E-loaded lipid nanoparticles (VitE-HALNP) enhanced MSC viability, reduced oxidative stress levels, and improved lung repair and survival rates in a mouse model of LPS-induced acute lung injury. Moreover, our research explores the potential of combining lipid nanoparticles with thin-film polymer systems to develop a novel single-shot vaccine delivery platform called NECTAR (Nanofilms Embedded lipid nanoparticles for Controlled and TARgeted drug Delivery). This platform enables the controlled intermittent release of the CHIKV virus, providing long-term immunity. These investigations introduce a unique approach to drug delivery employing lipid nanoparticle-based systems, and the outcomes of this research carry substantial implications for creating innovative therapies for a wide variety of diseases

Subject Area

Chemical engineering|Nanoscience|Molecular chemistry

Recommended Citation

Porwal, Rashi, "Development of Lipid Nanoparticles Based Drug Delivery Systems Targeting Oxidative Stress for Disease Prevention and Therapy - Preeclampsia to Acute Lung Injury" (2023). ETD collection for University of Nebraska-Lincoln. AAI30487652.