The Biomedical Applications of Protein Microspheres
Kolbeck, Kenneth J.
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Permalink
https://hdl.handle.net/2142/84446
Description
Title
The Biomedical Applications of Protein Microspheres
Author(s)
Kolbeck, Kenneth J.
Issue Date
1999
Doctoral Committee Chair(s)
Kenneth S. Suslick
Department of Study
Chemistry
Discipline
Chemistry
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Health Sciences, Pharmacology
Language
eng
Abstract
Microspheres were produced containing a core of aqueous or organic liquids (i.e., microcapsules) or air (i.e., microbubbles). The microspheres were stabilized by a 60--100 nm protein shell (approximately 10 molecules). The small microsphere diameter (<5 microns) permitted the intravenous injection of microspheres, while the use of native protein in forming the microspheres prevented any significant immune response. We have synthesized microspheres that can be monitored with in vivo imaging techniques (MRI or X-ray) and microscopy. The distribution and circulation lifetime in the bloodstream was extended by modifying the microsphere surface properties. The microspheres were evaluated as potential agents in histology, radiology, and pharmacology. Histologically, the microspheres were shown to localize within the liver and spleen (organs rich in phagocytic cells) without disrupting the normal tissue structure. Optical microscopy with Prussian blue staining, fluorescence microscopy, and electron microscopy techniques have confirmed the phagocytosis and digestion of intravenous microspheres. Radiological (X-ray and MRI) methods also confirmed the uptake in the liver and spleen. Microspheres carrying roentgenographic agents and MRI agents (T 1 and T2 agents for proton MRI and fluorine compounds for 19F MRI) have applications in imaging tissues with abnormal distributions of phagocytes. Pharmacologically, the unmodified microspheres were rapidly cleared from the blood stream while surface modification did increase the circulation half-life. The air-filled albumin and hemoglobin microbubbles were evaluated for potential oxygen delivery vehicles with mixed results. Although large numbers of microspheres can be safely introduced into the circulatory system, the current formulations do not carry enough oxygen to be effective in oxygen therapeutics.
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