Applications of multifunctional poly(glycidyl methacrylate) (PGMA) nanoparticles in enzyme stabilization and drug delivery

Research output: ThesisDoctoral Thesis

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Abstract

Nanotechnology, although a science in its infancy, has the potential to revolutionize the medical profession by improving on traditional drug delivery methods and transforming how disease and injury are currently diagnosed, monitored and treated. The effective delivery of small molecule drugs, peptides and proteins to a diseased or injury site has faced considerable barriers in the past including premature clearance from the body, off site toxicity and poor bioavailability or pharmacokinetics. Nanoparticles can be used to help improve these characteristics by aiding delivery of therapeutics which otherwise show little efficacy without assisted delivery. In this work, poly(glycidyl methacrylate) (PGMA) nanoparticles have been synthesized as delivery vehicles incorporating a range of surface functionalities and imaging probes to allow successful tracking of these nanoparticles throughout testing. These delivery vehicles have been used in a range of applications suggesting the broad applicability and suitability of functionalized PGMA nanoparticles in medicine. The nanoparticles were shown to aid in the delivery of a therapeutic peptide to modulate activity of the L-type calcium channel of cardiac tissue as well as thermally stabilize industrially relevant enzymes through nanosurface interactions. Finally, the potential of the nanoparticle's as DNA delivery vectors for gene silencing in cancer models was investigated. Further to these three delivery applications of the functionalized PGMA nanoparticles, work will be presented herein on the development of a novel spectrophotometric assay suitable for the detection of the activity of the therapeutic enzyme chondroitinase ABC (chABC). This newly presented assay was superior when compared to the traditional methods used for detecting the activity of chABC. This assay was used to investigate a range of formulations including functionalized PGMA nanoparticles, in an attempt to stabilize the therapeutically relevant chABC at 37 °C, to prolong its activity and in turn improve its effectiveness as a therapeutic in the treatment of central nervous system injuries.
Original languageEnglish
QualificationDoctor of Philosophy
Publication statusUnpublished - 2013

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