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Title: Ultrasonic monitoring and processing of injectable micellular hydrogels for use in drug delivery
Author: Farrugia, Mario
Awarding Body: University of Nottingham
Current Institution: University of Nottingham
Date of Award: 2013
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Micellar hydrogels composed of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) tri-block copolymers are one of the most widely studied formulations for use in drug delivery applications. These systems can be injected into the body in a liquid form and then, in response to external stimuli, self-assemble into nano-sized micelles and fibres which ultimately aggregate to form a gel. Their aggregation behaviour and hence effectiveness as drug carriers are affected by the local thermal and ionic environment which is likely to be different from patient to patient and in the healthy as compared to diseased states. It is therefore timely that techniques to probe the aggregation behaviour of PEO-PPO-PEO tri-block copolymer hydro gels in vivo are developed. This thesis presents an ultrasound technique to study the phase behaviour of the PEO-PPO-PEO tri-block copolymer (Pluronic F127) hydro gels loaded with a model hydrophobic drug, pyrene, as a function of temperature. Ultrasound parameters of velocity and attenuation were both found to change with temperature and through validation with fluorescence spectroscopy techniques it was determined that the temperature dependent transitions in Pluronic solutions could be identified through analysis of the relative changes in ultrasound velocity and attenuation as a function of temperature. These transitions were more clearly detected through examination of the first and second derivatives of both ultrasound parameters with respect to temperature Apart from monitoring phase changes and the aggregation behaviour of hydrogels, ultrasound has also been increasingly used as an enhancement technique in order to aid the release of drugs from within the delivery system, to assist with intracellular and intravascular drug uptake and to help in aggregation behaviour of certain hydro gels. This thesis also presents a novel technique for simultaneously monitoring the mechanical effects of low frequency (24 kHz) ultrasound on the Pluronic F127 micellar system. Results show that this produces a decrease in ultrasonic velocity measurements without any significant temperature increases, pointing at increased swelling and viscosity (and hence aggregation) brought about by the mechanical rather than thermal ultrasound effects.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available