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- Genre: Academic theses
Description
Aqueous solutions of temperature-responsive copolymers based on N-isopropylacrylamide (NIPAAm) hold promise for medical applications because they can be delivered as liquids and quickly form gels in the body without organic solvents or chemical reaction. However, their gelation is often followed by phase-separation and shrinking. Gel shrinking and water loss is a major limitation to using NIPAAm-based gels for nearly any biomedical application. In this work, a graft copolymer design was used to synthesize polymers which combine the convenient injectability of poly(NIPAAm) with gel water content controlled by hydrophilic side-chain grafts based on Jeffamine® M-1000 acrylamide (JAAm). The first segment of this work describes the synthesis and characterization of poly(NIPAAm-co-JAAm) copolymers which demonstrates controlled swelling that is nearly independent of LCST. The graft copolymer design was then used to produce a degradable antimicrobial-eluting gel for prevention of prosthetic joint infection. The resorbable graft copolymer gels were shown to have three unique characteristics which demonstrate their suitability for this application. First, antimicrobial release is sustained and complete within 1 week. Second, the gels behave like viscoelastic fluids, enabling complete surface coverage of an implant without disrupting fixation or movement. Finally, the gels degrade rapidly within 1-6 weeks, which may enable their use in interfaces where bone healing takes place. Graft copolymer hydrogels were also developed which undergo Michael addition in situ with poly(ethylene glycol) diacrylate to form elastic gels for endovascular embolization of saccular aneurysms. Inclusion of JAAm grafts led to weaker physical crosslinking and faster, more complete chemical crosslinking. JAAm grafts prolonged the delivery window of the system from 30 seconds to 220 seconds, provided improved gel swelling, and resulted in stronger, more elastic gels within 30 minutes after delivery.
ContributorsOverstreet, Derek (Author) / Caplan, Michael (Thesis advisor) / Massia, Stephen (Committee member) / Mclaren, Alexander (Committee member) / Vernon, Brent (Committee member) / McLemore, Ryan (Committee member) / Arizona State University (Publisher)
Created2012
Description
Technology transfer hurdles constantly keep effective medical treatment from healthcare. One prevalent hurdle is that of cost. Regulation from any organization or entity can drive up cost and requires thorough review before implementation. For microspheres specifically, extensive research has been conducted to minimize variation in size. How variation effects drug delivery of microspheres, however, has not been studied in depth. In this study, a preliminary approach to modeling drug delivery in microspheres with a given log-normal distribution is reported. A design of experiment statistical analysis was performed using incremental values of mean and standard deviation. To estimate the rate of drug diffusing from the microspheres, a simplified Fick's second law was used. Various data types were considered and it was found that the shape factors which are related to mean and standard deviation fit the statistical analysis best. Using the shape factor data type, equation characteristics were identified and reported. It was seen that standard deviation has a greater influence on drug delivery than mean. A prediction expression is presented that can be used to identify the time it takes to get to 60% drug delivery and can be used in a scaled manner.
ContributorsNickle, Jacob Aaron (Author) / Vernon, Brent (Thesis advisor) / McLemore, Ryan (Committee member) / Beeman, Scott (Committee member) / Arizona State University (Publisher)
Created2021