| Summary: | Amphiphilic polymers have long been known to display associative effects which can be exploited in controlled release applications. In particular, controlled drug delivery can benefit from the biocompatible nature of many polymers, as well as evidence of membrane affinity. This thesis describes the study of a series of amphiphilic polymers with potential for use in pharmaceutical applications. The work has ranged from development of new polymer structures with physical characteristics which may aid controlled release, through studies of polymer-drug association and disassociation in solution, to development of controlled release formulations incorporating the polymers. Novel polymers combining the controlled release potential of Pluronic triblock copolymers with that of cyclodextrins have been synthesised, via "Click Chemistry". The specificity and strong driving force behind this mechanism ensure that the molecules react covalently, to leave the cyclodextrin cavity free for complexation and controlled release of guest molecules. Commercial (unmodified) Pluronics have also been studied with drug molecules in solution, using small-angle neutron scattering and pulsed-field gradient NMR. Ibuprofen has been found to act as a cosurfactant for the Pluronic, causing an increase in aggregation but a decrease in the critical micelle concentration and temperature. Release of ibuprofen from the micelles may be triggered by an increase in solution pH, which influences the dynamic equilibrium of ibuprofen between the solution and micellar phases. Finally, new graft copolymers of polyisoprene and poly( ethylene oxide) have been found to display interesting behaviour in aqueous solution. Despite showing limited aqueous solubility, the polymers can be solubilised either by addition of other surfactant molecules, or by pre-dissolution in methanol, which is believed to enable the hydrophilic graft segments to orient outwards. The graft copolymers are capable of stabilising hydrophobic drug molecules in aqueous solution, and have also been successfully incorporated into controlled release formulations for drug delivery.
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