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ELECTROSPRAYING EXTRACELLULAR MATRIX TO FORM NANOPARTICLESLink, Patrick 01 January 2017 (has links)
Chronic Obstructive Pulmonary Disease (COPD) is a leading cause of death worldwide. Alveolar wall destruction is a significant contributor to COPD. Inflammatory macrophages are a major source of the Extracellular Matrix (ECM) proteolysis. ECM breakdown causes air to get trapped in the alveoli, obstructing airflow. One step in curing COPD may be to convert inflammatory to pro-regenerative macrophages. Recently, decellularized ECM scaffolds have shown the ability to induce a pro-regenerative phenotype.
Yet these scaffolds are incapable for reaching the alveolar region of the lungs. To reach the alveolar region particles need a diameter of 1-5 μm or smaller than 300 nm. We used protein from decellularized lung tissue to create nanoparticles. By first digesting the protein in acid, we electrosprayed the solution into nanoparticles. The average size of the nanoparticles is 225 (± 67) nm, within the requirements to reach alveoli. However, another barrier exists for treating this disease. That barrier is mucus; mucus hypersecretion is another sign of COPD. The formed particles are capable of penetrating the mucus layer in COPD. After characterizing the particles, we began in vitro investigations. First, we measured cytotoxicity of the nanoparticles. In alveolar epithelial cells, adding nanoparticles to the media increased cellular proliferation. We then added the nanoparticles to isolated murine macrophages. The nanoparticles induced a pro-regenerative phenotypic shift in murine macrophages. These experiments reveal that these nanoparticles may become an effective treatment for degenerative lungs diseases, such as COPD, after further investigation.
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Effects of Binary Solvent System on Morphology of ParticlesBesana, Patrick 01 December 2015 (has links)
Recent advancements in cancer research has led to the synthesis of a new drug known as docetaxel. Meant to replace paclitaxel, its more natural counterpart whose ingredients are difficult to obtain, the drug is known to effectively treat a wide array of cancers, including breast cancer, ovarian cancer, and prostate cancer. The establishment of a synthetic alternative to paclitaxel has increased its bioavailability, thereby lowering the cost needed to utilize the drug. Still, the limiting factor in minimizing costs is the method in which the drug is processed. Current methods in drug processing have their limitations, which include the introduction of impurities and a low effective yield due to poor powder geometry. Thus, the goal of this study looks to explore a new way to process the drug in a more efficient manner. In this study, a new method for processing docetaxel is explored on in great detail. A more direct method of using electrospray deposition is utilized for the creation of monodisperse nanoparticles, with the main intention of increasing the efficiency at which the drug is processed and prepared for drug delivery to the patient by means of injection. A key feature in electrospray deposition is its ability to produce droplets that are sized homogenously. These droplets eventually evaporate at homogenous rates. These two concepts have been exploited to consistently produce nanoparticles of the cancer drug, which is made possible by the fact that the minimal variation in droplet sizes has easily translated to minimal variation in dry particle sizes. Compared to other methods of drug processing, one other benefit that electrospray deposition conveys is that through evaporation, virtually all impurities and unwanted foreign material are eliminated.
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