Engineering polyanhydride microspheres for the stabilization and controlled release of proteins

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Determan, Amy
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Balaji Narasimhan
Marit Nilsen-Hamilton
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Chemical and Biological Engineering

The function of the Department of Chemical and Biological Engineering has been to prepare students for the study and application of chemistry in industry. This focus has included preparation for employment in various industries as well as the development, design, and operation of equipment and processes within industry.Through the CBE Department, Iowa State University is nationally recognized for its initiatives in bioinformatics, biomaterials, bioproducts, metabolic/tissue engineering, multiphase computational fluid dynamics, advanced polymeric materials and nanostructured materials.

The Department of Chemical Engineering was founded in 1913 under the Department of Physics and Illuminating Engineering. From 1915 to 1931 it was jointly administered by the Divisions of Industrial Science and Engineering, and from 1931 onward it has been under the Division/College of Engineering. In 1928 it merged with Mining Engineering, and from 1973–1979 it merged with Nuclear Engineering. It became Chemical and Biological Engineering in 2005.

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1913 - present

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  • Department of Chemical Engineering (1913–1928)
  • Department of Chemical and Mining Engineering (1928–1957)
  • Department of Chemical Engineering (1957–1973, 1979–2005)
    • Department of Chemical and Biological Engineering (2005–present)

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This work investigates the use of polyanhydride microspheres as drug delivery carriers for therapeutic proteins. The polymers investigated are poly(sebacic anhydride) and opolymers of poly[1,6-bis(p-carboxyphenoxy)hexane] (poly(CPH)) and poly(SA), 20:80 (CPH:SA), 50:50 (CPH:SA), and 80:20 (CPH:SA). The model protein bovine serum albumin (BSA) was encapsulated in poly(SA), 20:80 (CPH:SA), 50:50 (CPH:SA), and 80:20 (CPH:SA) microspheres to determine the feasibility of using polyanhydrides as protein carriers. Poly(SA) and 20:80 (CPH:SA) were found to stabilize the encapsulated BSA and were used for all future studies. The compatibility of three proteins (ovalbumin, lysozyme, and tetanus toxoid) with polyanhydride or polyester degradation products was invested. This work provided a rational approach for selecting compatible protein/polymer systems prior to encapsulating a protein in a polymer system. Four different microsphere fabrication techniques (water-oil-water, water-oil-oil, solid-oil-oil, and a cryogenic atomization method) were used to encapsulate ovalbumin in polyanhydride microspheres. The in vitro release kinetics, encapsulation efficiencies, and structural stability of the encapsulated and released ovalbumin were investigated. The cryogenic atomization method was determined to be superior and was used in future applications. The therapeutic protein, uterocalin, was encapsulated in polyanhydride microspheres and its biological activity upon release in vitro was measured. Uterocalin released from poly(SA) and 20:80 (CPH:SA) microspheres was biologically active. This work demonstrates that polyanhydrides microspheres are suitable drug delivery devices for therapeutic proteins.

Sun Jan 01 00:00:00 UTC 2006