Drug Delivery in Cardiovascular System with Multi Scale Approach

Rahmati, Mahmood | 2014

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  1. Type of Document: M.Sc. Thesis
  2. Language: Farsi
  3. Document No: 45919 (06)
  4. University: Sharif University of Technology
  5. Department: Chemical and Petroleum Engineering
  6. Advisor(s): Vosughi, Manouchehr; Saeedi, Mohammad Saeed; Firoozabadi, Bahar
  7. Abstract:
  8. Particle retention and clearance is a major concern in the treatment of pulmonary diseases. Inhaled materials into the nasal and lung airways include gases/vapors, liquid droplets and soluble/insoluble particulate matter which can be toxic or therapeutic (or both). For example, nanoparticles (NPs), as part of nanomedicine, are now being used as drug carriers for passive and active targeting of solid tumors and inflamed tissue. However, natural and especially manmade NPs can also be harmful, such as carbon nanotubes (CNTs), asbestos fibers and ambient toxic pollutants, based on epidemiological and pathological studies of occupational and environmental exposures. In fact, ultrafine particles have been found to pose a higher toxicity impact than larger particles made of the same material, mainly due to the more uniform deposition patterns in lung airways and easier migration across several barriers into the systemic system. Thus, investigations related to the deposition and removal of inhaled nanomaterial are of great importance because accumulation and retention of toxic NPs can result in serious lung diseases, e.g., chronic bronchitis, lung fibrosis, silicosis, asbestosis, lung cancer, etc. In case of polymeric nanostructures for disease detection, imaging and drug targeting, a thorough knowledge base of multifunctional nanoparticle formulation, delivery and uptake is crucial as well. Mathematical models and associated computer simulations, which can predict realistic particulate lung burden for specific parameters of exposure conditions, can offer valuable assistance in developing new preventive strategies. Optimal drug-aerosol targeting requires suitable physical drug-particle characteristics, appropriately controlled delivery to a predetermined site, and an accurate assessment of the deposited medicine. Given realistic local (or regional) NP-depositions, computer simulations of nanomaterial transfer from the lung airways ultimately into organs (or tumors) are important for both application areas. In this study a multi-compartmental model representing the bio-kinetics of nanoparticle translocation and retention in key segments of the human lung as well as connected tissue and vasculature was created. The model describes via a set of differential equations the transfer of nanomaterial between compartments, i.e., lung airway, mucus layer, epithelial barrier, capillaries, arteries, and organs. The initial deposition of nanoparticles in key segments of the human lung and upper airways was calculated using Computational Fluid-Particle Dynamics. This study provides critical insight into nanomaterial deposition in lung airways and distribution to systemic regions from lungs. The results of this study can be used in fields like toxicology and pharmacology, to analyze risk to a given nanomaterial exposure and assist in developing new pulmonary drugs
  9. Keywords:
  10. Nanoparticles ; Lung ; Cardiovascular System ; Multiscale Method ; Drug Delivery ; Multi-Compartmental Model

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