Synthesis and characterisation of novel n-vinyl pyrrolidinone/acrylic acid copolymers for use in biomedical applications.

Abstract

The aim of this study was to develop a novel hydrophilic polymer for use in biomedical applications. The polymers synthesised in this work were based on the monomers N-vinyl pyrrolidinone (NVP) and acrylic acid (AA) and were UV polymerised using a suitable photoinitiator depending upon the application. These polymers were analysed both with and without the incorporation of chemical crosslinking agents using a variety of test methods. From these tests it was found that the incorporation of AA imparted pH sensitivity to the hydrogel, which had a critical pH range of between 4.07 and 4.49. Above a pH of 4.49 there is a progressive break up of the polymer chain due to a reduction in the amount of intermolecular hydrogen bonding. There is also a significant increase in the polymer solubility and swelling of the crosslinked polymers at higher pHs. The Ftir spectra of PVP-PAA copolymer complexes indicates the presence of hydrogen bonding between the carbonyl group in the PVP and the carboxylic acid group in the PAA moiety, and the formation of an AA dimer. The incorporation of crosslinking agents caused a reduction in hydrogen bonding, signifying that crosslinking agents acted as a spacer between molecular chains. These polymers were physically characterised using parallel plate rheometry. The rheometry results indicated that there was a significant difference in the oscillating torque at break and the comparative strength of the hydrogels at different pHs, due to the increased water uptake. It was also found that by varying the molecular weight of the crosslinking agent, oscillating torque at break and the comparative strength of the hydrogels could be altered. After the initial characterisation of the hydrogels had taken place, suitable hydrogels were chosen for further analysis for specific applications. A chemically crosslinked monomeric mixture of 70-30 wt% NVP-AA was tested as a drug eluting lubricious hydrophilic coating that could be cured directly onto a substrate (Pebax ® 3533) without the aid of a solvent, using a dip coating/UV curing procedure. Ftir analysis illustrated that no characteristic monomeric peaks were found, and that curing the coating directly onto a substrate did not affect the chemical structure of the crosslinked polymer when compared to the Ftir spectrum of the polymer cured in bulk. Optical microscopy suggested that 2 coating cycles yielded the most consistent coating throughout the entire length of the substrate. Frictional analysis confirmed the lubricious nature of the coating, and showed that a dramatic reduction in the instantaneous force and kinetic force required to move a sample of Pebax ® 3533 was observed with the incorporation of the hydrated coating. Drug release analysis showed that the release of an active agent could be controlled by varying the molecular weight of the crosslinking agent used. The extractable content of the crosslinked hydrogels was analysed in relation to increasing crosslinking agent content. It has been shown that the extractable content of these hydrogels is relatively low, allowing these hydrogels to be used in applications where this is advantageous. We have demonstrated that the dissolution profile of active agents from these polymers vary, depending upon the dissolution media used. Finally, favourable cytotoxicity and genotoxicity results have been obtained proving that these novel polymers have potential in a variety of biomedical applications.