Degree Type

Dissertation

Date of Award

2006

Degree Name

Doctor of Philosophy

Department

Chemical and Biological Engineering

First Advisor

Balaji Narasimhan

Second Advisor

Marit Nilsen-Hamilton

Abstract

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.

DOI

https://doi.org/10.31274/rtd-180813-12290

Publisher

Digital Repository @ Iowa State University, http://lib.dr.iastate.edu/

Copyright Owner

Amy Sywassink Determan

Language

en

Proquest ID

AAI3217264

File Format

application/pdf

File Size

183 pages

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