• Login
    View Item 
    •   Home
    • Graduate Theses, Dissertations and Projects
    • Queen's Graduate Theses and Dissertations
    • View Item
    •   Home
    • Graduate Theses, Dissertations and Projects
    • Queen's Graduate Theses and Dissertations
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    In Vitro Simulation of In Vivo Performance of Oral Dosed Nanoparticulate Insulin

    Thumbnail
    View/Open
    Golkaran_Donya_201308_MSC.pdf (1.196Mb)
    Date
    2013-08-26
    Author
    Golkaran, Donya
    Metadata
    Show full item record
    Abstract
    The aim of this study was to evaluate the factors, which affect insulin release and stability in simulated gastrointestinal fluid that ultimately will reduce the bioavailability of insulin in a nanoparticulate oral delivery system. The focus was on nanoparticulate carriers developed by C. Reis, which have the highest level of bioavailability reported in the literature thus far.

    Particles observed by TEM were spherical and particle analyzer data showed that the peak of the distribution was 10 nm. Entrapment efficiency of insulin was 85%. Insulin retention/release was evaluated in both enzymatic and enzyme-free simulated digestive fluids. HPLC measurement showed that insulin was stable in acid condition in presence and absence of pepsin. By changing the pH to 6.8 in an intestinal simulation, the amount of insulin decreased such that at the end of the 5 h simulation, 71% of the insulin was measureable in simulated GI fluid in presence of enzymes.

    Insulin release profile from nanoparticles was low in gastric condition. After changing the pH to 6.8, an initial release of insulin occurred in the first 1h followed by plateau state in the remaining 2h. After a total of 5h in acidic followed by neutral pH medium, the formulation retained 48% of the insulin in the particles in simulated GI fluid in presence of enzyme. As confirmation of the amount of retained insulin, after 5h, particles were dissolved and the formulation was shown to fully retain up to 45% of the insulin in extended simulated gastrointestinal condition in the presence of enzymes.

    Insulin release behavior was investigated in different simulated small intestinal media by incorporating phosphate buffer or bicarbonate buffer and physiological electrolytes. The release rate from particles in the phosphate buffer was faster compared to bicarbonate buffers. KBB-C showed a release profile that was very different from other media, with about 10% released in the first 30 min and 70% of the insulin remaining entrapped within the particles at the end of the experiment. Release in this buffer was reduced due to the decreased sodium to calcium ratio compared to the other KBB media.
    URI for this record
    http://hdl.handle.net/1974/8211
    Collections
    • Queen's Graduate Theses and Dissertations
    • Department of Chemical Engineering Graduate Theses
    Request an alternative format
    If you require this document in an alternate, accessible format, please contact the Queen's Adaptive Technology Centre

    DSpace software copyright © 2002-2015  DuraSpace
    Contact Us
    Theme by 
    Atmire NV
     

     

    Browse

    All of QSpaceCommunities & CollectionsPublished DatesAuthorsTitlesSubjectsTypesThis CollectionPublished DatesAuthorsTitlesSubjectsTypes

    My Account

    LoginRegister

    Statistics

    View Usage StatisticsView Google Analytics Statistics

    DSpace software copyright © 2002-2015  DuraSpace
    Contact Us
    Theme by 
    Atmire NV