Solid Lipid Nanoparticle-Based Drug Delivery for Lung Cancer
Nazrul Islam in Handbook of Lung Targeted Drug Delivery Systems, 2021
Lung cancer is also known as lung carcinoma and is a malignant form of lung tumor characterized by uninhibited cell growth in lung tissues. Internationally, lung cancer remains the main cause of cancer-related mortality in females and males. Nanomaterials of size range 10–200 nanometers in diameter are called nanocarriers and they are believed to be a possible vehicle for drug delivery. Solid lipid nanoparticles (SLNs) as nanocarriers have reduced the cytotoxicity of anti-tumor drugs and experiments have been performed which show improved therapeutic efficacy of drugs used in treatment of lung cancer. This chapter highlights the epidemiology and current management of lung cancer, role of nanocarriers in treating lung cancer, role of SLNs in drug delivery for treatment of lung cancer, ligand anchored SLNs, administration of SLNs by pulmonary drug delivery system, and the role of SLNs for gene delivery, combinatorial drug delivery, and the toxicological evaluation of SLNs.
Modeling of Pharmaceutical Aerosol Transport in the Targeted Region of Human Lung Airways Due to External Magnetic Field
Nazrul Islam in Handbook of Lung Targeted Drug Delivery Systems, 2021
Inhalation of aerosol is a substantiative technique for drug delivery in lungs. Aerosolized drug inhalation and delivery through oral and arterial routes plays an important role for the treatment of respiratory diseases. This chapter conducts a comprehensive numerical modeling of pharmaceutical particle transport and deposition processes in a target location of the lung. Human lung models are often used to demonstrate particle deposition in the targeted region by applying numerical methods. Based on the inlet flow rate conditions, the flow through airways of a human lung can be modeled as laminar, transitional, or turbulent. The atmospheric airborne particles’ size distribution consists of a significant amount of fine and ultrafine particles which are generally smaller than a couple of microns. A numerical model for microparticle transport and deposition in the targeted region of human lungs due to an external magnetic field has been developed for a triple bifurcation lung airway.
Modeling for Biopharmaceutical Performance in Lung Drug Discovery
Nazrul Islam in Handbook of Lung Targeted Drug Delivery Systems, 2021
In lung drug discovery, modeling and simulation play important roles as the lungs are one of the most complex organs in the body. By using modeling and simulation, drug developers can predict drug effectiveness. The models and simulations based on computed tomography scans work well to understand the complexities in lifelong diseases such as asthma and chronic obstructive pulmonary disease. Stem cells have the ability to become any cell in the body, which aids in the process of cellular modeling. Molecular dynamics simulations show meticulously replicated membrane proteins and let researchers see how the proteins work together when introduced to medications. By studying simulations, it is possible to understand the effects of certain drugs on the organ. The benefits with in vitro models are that scientists have been able to understand the way that human lungs maintain homeostasis and how the lack of some cellular processes can have detrimental effects on the organ.
TRANSFORMING GROWTH FACTOR β CONTRIBUTES TO LUNG LEAK IN RATS GIVEN INTERLEUKIN-1 INTRATRACHEALLY
Published in Experimental Lung Research, 2003
Brooks M. Hybertson, Eric K. Jepson, Jenny D. Allard, Okyong J. Cho, Young M. Lee, Jennifer R. Huddleston, Jason P. Weinman, Anthony M. Oliva, John E. Repine
Interleukin-1 (IL-1) is increased in lung lavages obtained from patients with acute lung injury (ALI) and administering recombinant human IL-1 α (rhIL-1 α) (50 ng) intratracheally causes an acute, neutrophil-dependent, oxidative lung leak in rats that closely resembles human ALI. In the present work, the authors tested the hypothesis that transforming growth factor β (TGF β) contributes to the lung inflammation and injury that develops in rats given IL-1 intratracheally. They found that intravenous administration of a monoclonal antibody to TGF β (1.D.11.16, 0.5 mg/kg) attenuated lung injury responses, specifically lung leak index, lung lavage protein concentrations, and blood oxygenation abnormalities, that are observed 5 hours after intratracheal instillation of IL-1 in rats, but did not decrease indices of lung inflammation, specifically myeloperoxidase (MPO) activity in lung tissue, neutrophil counts in lung lavage, and cytokine-induced neutrophil chemoattractant (CINC) levels in lung lavage, in rats given IL-1 intratracheally. The results suggest that TGF β contributes to lung leak, but not lung inflammation, following intratracheal administration of IL-1 in rats.
SERUM FERRITIN ELEVATION AND ACUTE LUNG INJURY IN RATS SUBJECTED TO HEMORRHAGE: REDUCTION BY MEPACRINE TREATMENT
Published in Experimental Lung Research, 2004
Yoon-yub Park, Brooks M. Hybertson, Richard M. Wright, Mehdi A. Fini, Nancy D. Elkins, John E. Repine
□ Ferritin regulates iron levels and, for unknown reasons, serum ferritin concentrations are increased in patients at risk for and with acute lung injury (ALI) and multiple organ failure. Uncomplexed iron could exacerbate the toxicity of the increased oxidative stress that occurs in patients with ALI and multiple organ failure and thereby contribute to disease. In the present investigation, the authors found that serum and lung lavage ferritin concentrations increased in hemorrhaged rats that develop ALI as manifested by increased lung inflammation (increased lung lavage leukocyte counts and lung myeloperoxidase activities) and increased lung leak (increased lung lavage protein concentrations). Treatment with mepacrine, a phospholipase A2 inhibitor, attenuated the increases in serum and lung lavage ferritin concentrations, lung inflammation, and lung leak that occur in rats subjected to hemorrhage. The findings show that serum and lung ferritin levels increase and may play a role in the development of acute lung injury caused by hemorrhage.
High-frequency oscillation combined with arteriovenous extracorporeal lung assist reduces lung injury
Published in Experimental Lung Research, 2010
Ralf M. Muellenbach, Markus Kredel, Jochen Wilhelm, Julian Küstermann, Ludger Fink, Gregor Siebenliest, Bernd Klosterhalfen, Carola Y. Foerster, Peter Kranke, Christian Wunder, Norbert Roewer, Jörg Brederlau
ABSTRACT In order to optimize the lung-protective potential of high-frequency oscillatory ventilation (HFOV), it is currently recommended to maximize oscillatory frequencies. However, very high frequencies may lead to insufficient CO2 elimination with severe respiratory acidosis. Arteriovenous extracorporeal lung assist (av-ECLA) allows near total CO2 removal, thereby allowing for maximization of the lung-protective potential of HFOV. The aim of this study was to determine the impact of HFOV and av-ECLA on lung inflammation and function compared to conventional lung-protective ventilation. In a porcine surfactant depletion model of lung injury, the authors randomly assigned 16 female pigs to conventional lung-protective ventilation and HFOV/ECLA. Both strategies were combined with an “open-lung” approach. Gas exchange and hemodynamic parameters were measured at intervals during the 24-hour study period. Postmortem, lung tissue was analyzed to determine histological damage and lung inflammation. The authors found that the combination of HFOV and av-ECLA (1) allows significant reductions in mean and peak airway pressures; and (2) reduces histological signs of lung inflammation in the basal regions of the lung. HFOV/av-ECLA reduces histological signs of lung inflammation compared to conventional lung-protective ventilation strategies. Thus, combination of HFOV and av-ECLA might be a further lung-protective tool if conventional ventilation strategies are failing.
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