Mass Production and Size Control of Lipid–Polymer Hybrid Nanoparticles through Controlled Microvortices

Lipid–polymer hybrid (LPH) nanoparticles can deliver a wide range of therapeutic compounds in a controlled manner. LPH nanoparticle syntheses using microfluidics improve the mixing process but are restricted by a low throughput. In this study, we present a pattern-tunable microvortex platform that allows mass production and size control of LPH nanoparticles with superior reproducibility and homogeneity. We demonstrate that by varying flow rates (i.e., Reynolds number (30–150)) we can control the nanoparticle size (30–170 nm) with high productivity (~3 g/hour) and low polydispersity (~0.1). Our approach may contribute to efficient development and optimization of a wide range of multicomponent nanoparticles for medical imaging and drug delivery.National Heart, Lung, and Blood Institute (Program of Excellence in Nanotechnology (PEN) Award Contract HHSN268201000045C)National Cancer Institute (U.S.) (Grant P01 CA151884)Prostate Cancer Foundation (Award in Nanotherapeutics

Theranostic nanoparticles for the management of inflammatory diseases and conditions

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Chemical Engineering, 2017.Cataloged from PDF version of thesis.Includes bibliographical references.Atherosclerosis, the gradual buildup of plaques within arteries, is the main cause of cardiovascular diseases (CVDs). The World Health Organization reports that CVDs are the number one cause of death in the world. In the United States alone, around 85 million people suffer from CVDs; this is associated with a cost of over $316 billion per year and responsible for about a third of all deaths in the US. Recent findings have shown that inflammation plays a pivotal role in atherosclerosis. Although statins have traditionally been prescribed for their lipid-lowering benefits, studies have indicated that they can have other effects as well (so-called "pleiotropic effects"), including anti-inflammatory, anti-oxidant, and anti-thrombotic benefits. This thesis presents a novel theranostic (therapeutic + diagnostic) nanoparticle platform for the treatment and diagnosis of atherosclerosis. Given the anti-inflammatory effects of statins when cells are directly treated, the aim of this nanoparticle platform was to target macrophages within plaques given their central role in plaque development and progression. First, simvastatin-loaded nanoparticles were designed and optimized. The particles consisted of a biodegradable polymer core and a lipid shell. Using bulk nanoprecipitation methods, as well as microfluidic devices, the physical characteristics of the particles could be controlled and fine-tuned to meet the desired specifications: 100 to 200 nm in size, -15 to -20 mV in zeta potential, and 70%+ simvastatin loading efficiency. Imaging agents, such as iron oxide nanocrystals used for magnetic resonance imaging (MRI), were successfully incorporated into the nanoparticles and can offer diagnostic capabilities to the nanoparticles. Next, various nanoparticle formulations were shown to be therapeutically effective in cell and mice models of atherosclerosis. For instance, in vitro treatment of macrophages led to decreases in the expression of TNF-a and MCP-1 by roughly 20% and 50%, respectively. This pattern has also been observed in murine models, with researchers showing that simvastatin-loaded particles can halt plaque development (and even decrease plaque area) while reducing the expression of pro-inflammatory genes (e.g., of TNF-a, IL- IP) by an order of magnitude. Overall, this thesis presents a new and innovative nanoparticle platform that has the potential for the simultaneous treatment and diagnosis of atherosclerosis. Given their anti-inflammatory benefits, these nanoparticles have the potential to impact the treatment of not only atherosclerosis but also various other inflammatory conditions and diseases as well.by Bomy Lee Chung.Ph. D

Optimization of the production of Maleated Polypropylene for Use in VRLA Batteries

Presented on April 30, 2010 from 11:00am - 01:00pm in room L1255 of the Ford Environmental Science & Technology (ES&T) Building.Group 11Runtime: 16:46 minute

Nanomedicines for endothelial disorders

The endothelium lines the internal surfaces of blood and lymphatic vessels and has a critical role in maintaining homeostasis. Endothelial dysfunction is involved in the pathology of many diseases and conditions, including disorders such as diabetes, cardiovascular diseases, and cancer. Given this common etiology in a range of diseases, medicines targeting an impaired endothelium can strengthen the arsenal of therapeutics. Nanomedicine - the application of nanotechnology to healthcare - presents novel opportunities and potential for the treatment of diseases associated with an impaired endothelium. This review discusses therapies currently available for the treatment of these disorders and highlights the application of nanomedicine for the therapy of these major disease complications. Keywords: Endothelium; Nanomedicine; Endothelial disorder; Diabetes; Atherosclerosis; CancerNational Heart, Lung, and Blood Institute (Contract HHSN268201000045C)National Institutes of Health (U.S.) (Contract HHSN268201000045C)National Cancer Institute (U.S.) (Grant CA151884

Mass Production and Size Control of Lipid–Polymer Hybrid Nanoparticles through Controlled Microvortices

Lipid–polymer hybrid (LPH) nanoparticles can deliver a wide range of therapeutic compounds in a controlled manner. LPH nanoparticle syntheses using microfluidics improve the mixing process but are restricted by a low throughput. In this study, we present a pattern-tunable microvortex platform that allows mass production and size control of LPH nanoparticles with superior reproducibility and homogeneity. We demonstrate that by varying flow rates (i.e., Reynolds number (30–150)) we can control the nanoparticle size (30–170 nm) with high productivity (∼3 g/hour) and low polydispersity (∼0.1). Our approach may contribute to efficient development and optimization of a wide range of multicomponent nanoparticles for medical imaging and drug delivery

Probing nanoparticle translocation across the permeable endothelium in experimental atherosclerosis

Therapeutic and diagnostic nanomaterials are being intensely studied for several diseases, including cancer and atherosclerosis. However, the exact mechanism by which nanomedicines accumulate at targeted sites remains a topic of investigation, especially in the context of atherosclerotic disease. Models to accurately predict transvascular permeation of nanomedicines are needed to aid in design optimization. Here we show that an endothelialized microchip with controllable permeability can be used to probe nanoparticle translocation across an endothelial cell layer. To validate our in vitro model, we studied nanoparticle translocation in an in vivo rabbit model of atherosclerosis using a variety of preclinical and clinical imaging methods. Our results reveal that the translocation of lipid–polymer hybrid nanoparticles across the atherosclerotic endothelium is dependent on microvascular permeability. These results were mimicked with our microfluidic chip, demonstrating the potential utility of the model system.National Heart, Lung, and Blood Institute (Contract HHSN268201000045C)National Cancer Institute (U.S.) (Grant CA151884)Prostate Cancer Foundation (Award in Nanotherapeutics