• Login
    View Item 
    •   Home
    • UA Graduate and Undergraduate Research
    • UA Theses and Dissertations
    • Dissertations
    • View Item
    •   Home
    • UA Graduate and Undergraduate Research
    • UA Theses and Dissertations
    • Dissertations
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of UA Campus RepositoryCommunitiesTitleAuthorsIssue DateSubmit DateSubjectsPublisherJournalThis CollectionTitleAuthorsIssue DateSubmit DateSubjectsPublisherJournal

    My Account

    LoginRegister

    About

    AboutUA Faculty PublicationsUA DissertationsUA Master's ThesesUA Honors ThesesUA PressUA YearbooksUA CatalogsUA Libraries

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    Synthesis, Comprehensive Characterization, and Development of Therapeutic Peptides and Glycopeptides for Targeted Respiratory Drug Delivery as Inhalation Aerosols

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    azu_etd_19189_sip1_m.pdf
    Embargo:
    2023-10-11
    Size:
    11.11Mb
    Format:
    PDF
    Download
    Author
    Alabsi, Wafaa Mohammad Alsghaeer
    Issue Date
    2021
    Advisor
    Mansour, Heidi
    Polt, Robin
    
    Metadata
    Show full item record
    Publisher
    The University of Arizona.
    Rights
    Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction, presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
    Embargo
    Release after 10/11/2023
    Abstract
    Central nervous system (CNS) disorders, including neurodegeneration and chronic pain, and many respiratory diseases would greatly benefit from the specific and potent peptide pharmaceuticals and their low inherent toxicity. The delivery of peptides to target the brain is challenging, principally due to peptides' low metabolic stability, which decreases their duration of action, poor penetration of the blood-brain barrier (BBB), and their incompatibility with oral administration, typically resulting in the need for parenteral administration. These challenges limit the clinical application of peptides and explain the interest for alternative routes of peptide administration, particularly: delivery to the respiratory tract (upper and lower). Upper to target the brain through the olfactory route bypassing the blood-brain barrier (BBB), i.e., needle-free nose-to-brain delivery (N-to-B), which offers protein and peptide drugs the possibility to reach the brain noninvasively. N-to-B delivery can be a convenient method for rapidly targeting the CNS, bypassing the BBB, and minimizing systemic exposure. In addition, delivery to the lower respiratory tract as inhalation aerosol offers attractive advantages in delivering the drug locally to treat lung diseases; and to the CNS to treat its disorders at a low dose while minimizing systemic adverse effects. The lung is a low metabolic organ compared to the gastrointestinal (GI) tract. It allows rapid and high drug absorption due to the large surface area, the high blood flow, and the absence of the first-pass metabolism. In this study, several peptides and glycopeptides with different pharmacological mechanisms were developed. Some of these compounds were synthesized using the SPPS strategy and formulated as dry powders with characteristics tailored to target the respiratory tract (upper and/or lower) to treat various CNS and lung diseases. Advanced organic closed mode spray drying technique was used to produce microparticulate/ nanoparticulate formulations utilizing sugar-based excipients. The solubility and lipophilicity of all included compounds were determined computationally using molecular operating environment (MOE) software and experimentally using the shake-flask method (SFM). The raw and formulated compounds were comprehensively characterized in the solid-state. The safety of all peptides and glycopeptides covered in this dissertation was evaluated in vitro using the human nasal, brain, and pulmonary cell lines. The in vitro aerosol dispersion of the raw and spray-dried compounds was tested using an FDA-approved human inhaler device, and the influence of spray drying process conditions on the aerosol dispersion was evaluated.
    Type
    text
    Electronic Dissertation
    Degree Name
    Ph.D.
    Degree Level
    doctoral
    Degree Program
    Graduate College
    Pharmaceutical Sciences
    Degree Grantor
    University of Arizona
    Collections
    Dissertations

    entitlement

     
    The University of Arizona Libraries | 1510 E. University Blvd. | Tucson, AZ 85721-0055
    Tel 520-621-6442 | repository@u.library.arizona.edu
    DSpace software copyright © 2002-2017  DuraSpace
    Quick Guide | Contact Us | Send Feedback
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.