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Title: Interaction and biological activity of oxidation responsive polymers and aggregates
Author: El Mohtadi, Farah
ISNI:       0000 0004 6497 1973
Awarding Body: University of Manchester
Current Institution: University of Manchester
Date of Award: 2017
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The research presented in this thesis focuses on the molecular design of an oxidation sensitive polymer and its enzyme conjugate with a view of its application in the field of biomaterials. I have polarised our attention on a specific class of polymers, polysulfides, for their environmental responsiveness (towards oxidising substances, a condition often associated with inflammatory reactions), interesting physico-chemical properties, ease of the preparation and multiple possibilities for further modifications and bioconjugation, which are suitable for the development as systems for drug delivery applications. In this work I firstly have focused on the synthesis of poly(thioglycidyl glycerol) and its conjugation to lysozyme. This study was followed by an investigation of the effect of conjugation on the in vitro stability, and biological activity of the conjugated enzyme. In another part of the work, I have developed a micellar system from poly(propylene sulfide)-co-poly(ethylene sulfide)-co-poly(ethylene glycol) polymers unloaded and loaded with immunosuppressant drug (Rapamycin). Specifically, here I have demonstrated how this hybrid system can efficiently inhibit the progression of osteoclast activity in the bone remodelling process seen in osteoporosis sufferers. In another chapter, I have designed a water soluble polysulfide which can be used as alternative to PEG. Poly(propylene sulfide) was synthesised via anionic ring opening polymerisation using S-methyl thioacetate as initiator. The synthesised polymer was then oxidised via hydrogen peroxide (H2 O2). The resultant water soluble polymer was tested for its toxicity and complement activation, and it has shown a toxicity profile identical to that of PEG with lesser extent of complement activation.
Supervisor: Stratford, Ian Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available