Albumin-heparin in microspheres for drug delivery

Update Item Information
Publication Type dissertation
School or College College of Pharmacy
Department Pharmaceutics & Pharmaceutical Chemistry
Author Kwon, Glen Sung Soo
Title Albumin-heparin in microspheres for drug delivery
Date 1991-08
Description Albumin-heparin microspheres have been prepared as an injectable, biodegradable drug delivery system. First, the soluble albumin-heparin conjugate was synthesized and purified by ion exhange and affinity liquid chromatography. The composition of the conjugate was established by amino acid analysis. Microspheres of the conjugate were prepared by crosslinking of the conjugate in a water in oil emulsion and characterized in terms of size, swelling and surface properties. Initial release experiments from albumin-heparin microspheres, using FITC-dextran as a model macromolecule, were carried out. The release of the macromolecule was modulated by crosslinking density, loading content and method of solute incorporation. Apparently, the mechanism of FITC-dextran release was dependent on the method of solute incorporation. The release of FITC-dextran from the microspheres was much more prolonged than the release of low molecular weight drugs from chemically crosslinked albumin microspheres and was attributed to the high molecular weight of the dextran. The release of macromolecules by ion exchange from albumin-heparin microspheres was investigated. Lysozyme, chicken egg and human, were used as positively charged model macromolecules due to their dissimilar properties and macromolecules due to their dissimilar properties and adsorptive behavior on polymer surfaces. Adsorption isotherms of the lysozymes on albumin-heparin and albumin microspheres were obtained. Higher loading of lysozyme into albumin-heparin microspheres relative to albumin microspheres was observed. Long term release of lysozymes from albumin-heparin and albumin microspheres was obtained. A mathematical model based on the Nernst-Planck equation was proposed for the release of the lysozyme from the microspheres. Apparent diffusion coefficients on the order of 10' to 10'^^ cmVsec were established for the release processes. The release was found not to be dependent on diffusion, but the rate determining step was likely adsorption/desorption processes. Overall, albumin-heparin microspheres demonstrated enhanced ion exchange properties over albumin microspheres. The released lysozyme was found to retain considerable enzymatic activity. The heparin of the albumin-heparin microspheres was determined to retain bioactivity and inhibit serine proteases of the blood coagulation cascade. The surface associated heparin accounted largely for the activity of the immobilized heparin of the microspheres. Platelet adhesion on albumin-heparin microspheres was lower compared to albumin microspheres and much lower than for polystyrene coated beads.""
Type Text
Publisher University of Utah
Subject Microspheres (Pharmacy); Albumins; Heparin
Subject MESH Microspheres; Albumins; Heparin; Pharmacology
Dissertation Institution University of Utah
Dissertation Name PhD
Language eng
Relation is Version of Digital reproduction of "Albumin-heparin in microspheres for drug delivery" Spencer S. Eccles Health Sciences Library.
Rights Management © Glen Sung Soo Kwon.
Format Medium application/pdf
Format Extent 3,184,390 bytes
Identifier undthes,3917
Source Original University of Utah Spencer S. Eccles Health Sciences Library (no longer available)
Master File Extent 3,184,436 bytes
ARK ark:/87278/s6pr7xtw
Setname ir_etd
ID 191391
Reference URL https://collections.lib.utah.edu/ark:/87278/s6pr7xtw