• 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

    Application of an in vitro cell monolayer model for evaluating the transport of a peptide and a mineral nutrient.

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    azu_td_9531072_sip1_c.pdf
    Size:
    4.535Mb
    Format:
    PDF
    Download
    Author
    Surendran, Narayanan.
    Issue Date
    1995
    Committee Chair
    Blanchard, James
    
    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 or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
    Abstract
    The overall objectives of this research is two-fold. First, preformulation studies of a novel chemopreventive peptide known as Melanotan-I (MT-I) were performed in order to facilitate the development of suitable formulations of this compound. The studies conducted include (a) the development of a HPLC assay in cell culture transport buffer and human plasma, (b) determination of its partitioning properties and stability kinetics in aqueous solutions, and (c) evaluation of transport properties using an in-vitro cell monolayer model consisting of Caco-2 cells grown as a monolayer on permeable supports. The HPLC method developed here was sensitive, specific and stability-indicating. This assay was successfully applied to the study of MT-I transport across Caco-2 cells. Partitioning of MT-I determined in n-octanol:buffer and isooctane:buffer solvent systems indicated the potential of delivering this peptide via the oral route. MT-I degradation in phosphate buffer exhibited apparent first order kinetics with an estimated shelf life of 40 days at room temperature. It was found to be relatively stable at acidic conditions but had an increased degradation rate at pH > 7.4. Transport of MT-I across Caco-2 cells indicated the degradation of this peptide by the proteases associated with the enterocyte to be the primary obstacle to its oral delivery. MT-I transport was significantly enhanced in the presence of a protease inhibitor (aprotinin). The second objective of this research was to identify enhancers of calcium transport using the in-vitro Caco-2 cell monolayer model. Both medium-chain triglycerides and acylcarnitines were found to enhance the transport of calcium, although to varying degrees. Acylcarnitines were found to be more potent enhancers of calcium transport, but a greater extent of cell damage was observed with their use. In addition, Caco-2 cells were shown to possess L-type calcium channels for the first time, and acylcarnitines were demonstrated to behave like calcium channel agonists similar to that of Bay K 8644 (an established channel agonist). Promotion of both transcellular (membrane perturbation) and paracellular (loosening of tight junctions) pathways of calcium transport were shown to be significant contributors toward the overall enhancement mediated by the acylcarnitines chosen for this study.
    Type
    text
    Dissertation-Reproduction (electronic)
    Degree Name
    Ph.D.
    Degree Level
    doctoral
    Degree Program
    Pharmaceutical Sciences
    Graduate College
    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.