The aim of this research was to prepare a series of molecularly imprinted polymers (MIPs) for corticosteroid templates using bulk and precipitation polymerisation strategies. Initially, a systematic study was undertaken, investigating the factors affecting the synthesis of MIPs by precipitation polymerisation. Careful optimisation of polymerisation parameters, including the monomer concentration, initiator type and solvent, allowed for a high degree of control over particle size and morphology. Preequilibrium interactions between the primary target budesonide (BDN) and functional monomers were investigated using NMR studies and showed weak interactions with dissociation constants, kdiss, ranging from 0.534-1.47 M Due to this weak functional monomer-template interaction, polymers were prepared in bulk format using a target analogue approach utilising hydrocortisone-17-butyrate (HCB) as a low-cost alternative to BDN. The HCB imprinted ground bulk polymers demonstrated imprinting factors (IF) as high as 7.5 for the template. Selectivity studies on six steroidal analogues showed that recognition was driven by shape and size selectivity as well as hydrophobic interactions, with IF values ranging from 1.2-9.5 in both organic and aqueous based systems. Applications of the imprinted polymers were demonstrated by solid-phase extraction (SPE) and analytical column chromatography. SPE studies utilising HCB imprinted polymers displayed a seven-fold increase in the specific retention of BDN. Precipitated prednisolone imprinted polymers achieved chromatographic separation between the template and hydrocortisone, a close structural analogue. Selectivity factors as high as 1.4 and a resolution value of 0.75 were achieved. Two custom functional monomer strategies were utilised towards enhancing MIP performance. The synthesis of tailor-made monomers based on derivatised cyclodextrins (CD) achieved a substitution of 2.5 polymerisable vinyl groups per CD. This derivatised CD was used to prepare precipitated polymers (0.3-7.2 μm) in a 40% aqueous acetonitrile porogen. A polymerisable hydrocortisone methacrylate monomer was successfully synthesised for use in semi-covalent imprinting which produced discrete microspherical beads (1.2-5.1 μm) using divinylbenzene as the crosslinker.
|Unpublished - 2011
- Polymers, Corticosteroids