Nicola Irwin

Synthesis and characterization of hyaluronic acid hydrogels crosslinked using a solvent-free process for potential biomedical applications

Graphical abstract

Infection-Responsive Drug Delivery from Urinary Biomaterials Controlled by a Novel Kinetic and Thermodynamic Approach

ABSTRACTPurposeThe pH-dependent physicochemical properties of the antimicrobial quinolone, nalidixic acid, were exploited to achieve ‘intelligent’ drug release from a potential urinary catheter coating, poly(2-hydroxyethylmethacrylate) (p(HEMA)), in direct response to the elevated pH which occurs at the onset of catheter infection.Methodsp(HEMA) hydrogels, and reduced-hydrophilicity copolymers incorporating methyl methacrylate, were loaded with nalidixic acid by a novel, surface particulate localization method, and characterized in terms of pH-dependent drug release and microbiological activity against the common urease-producing urinary pathogen Proteus mirabilis.ResultsThe pH-dependent release kinetics of surface-localized nalidixic acid were 50- and 10-fold faster at pH 9, representing the alkaline conditions induced by urease-producing urinary pathogens, compared to release at pH 5 and pH 7 respectively. Furthermore, microbiological activity against P. mirabilis was significantly enhanced after loading surface particulate nalidixic acid in comparison to p(HEMA) hydrogels conventionally loaded with dispersed drug. The more hydrophobic methyl methacrylate-containing copolymers also demonstrated this pH-responsive behavior, but additionally exhibited a sustained period of zero-order release.ConclusionsThe paradigm presented here provides a system with latent, immediate infection-responsive drug release followed by prolonged zero-order antimicrobial delivery, and represents an ‘intelligent’, infection-responsive, self-sterilizing biomaterial.

Effect of pH on the in vitro susceptibility of planktonic and biofilm-grown Proteus mirabilis to the quinolone antimicrobials.

To examine the effect of elevated pH, as reported during urinary catheter infections, on quinolone activity against the urease‐producing pathogen Proteus mirabilis.

Anti-Adherent Biomaterials for Prevention of Catheter Biofouling

Medical device-associated infections present a leading global healthcare challenge, and effective strategies to prevent infections are urgently required. Herein, we present an innovative anti-adherent hydrogel copolymer as a candidate catheter coating with complementary hydrophobic drug-carrying and eluting capacities. The amphiphilic block copolymer, Poloxamer 188, was chemically-derivatized with methacryloyl moieties and copolymerized with the hydrogel monomer, 2-hydroxyethyl methacrylate. Performance of the synthesized copolymers was evaluated in terms of equilibrium swelling, surface water wettability, mechanical integrity, resistance to encrustation and bacterial adherence, and ability to control release of the loaded fluoroquinolone antibiotic, ofloxacin. The developed matrices were able to provide significant protection from fouling, with observed reductions of over 90% in both adherence of the common urinary pathogen Escherichia coli and encrusting crystalline deposits of calcium and magnesium salts relative to the commonly employed hydrogel, poly (hydroxyethyl methacrylate). Additionally, the release kinetics of a loaded hydrophobic drug could be readily tuned through facile manipulation of polymer composition. This combinatorial approach shows significant promise in the development of suitable systems for prevention of catheter-associated infections.

Use of in vitro and haptic assessments in the characterisation of surface lubricity

Lubricity is a key property of hydrophilic-coated urinary catheter surfaces. In vitro tests are commonly employed for evaluation of surface properties in the development of novel catheter coating technologies; however, their value in predicting the more subjective feeling of lubricity requires validation. We herein perform a range of in vitro assessments and human organoleptic studies to characterise surface properties of developmental hydrophilic coating formulations, including water wettability, coefficient of friction, dry-out kinetics and lubricity. Significant reductions of up to 40% in the contact angles and coefficient of friction values of the novel coating formulations in comparison with the control poly(vinylpyrrolidone)-coated surfaces were demonstrated during quantitative laboratory assessments. In contrast, no significant differences in the more subjective feeling of lubricity between the novel formulations and the control-coated surfaces were observed when formulations were haptically assessed by the techniques described herein. This study, importantly, highlights the need for optimisation of in vitro and human haptic assessments to more reliably predict patient preferences.

Synthesis and characterization of lignin hydrogels for potential applications as drug eluting antimicrobial coatings for medical materials.

Lignin is the second most abundant biopolymer on the planet. It is a biocompatible, cheap, environmentally friendly and readily accessible material. It has been reported that these biomacromolecules have antimicrobial activities. Consequently, lignin (LIG) has the potential to be used for biomedical applications. In the present work, a simple method to prepare lignin-based hydrogels is described. The hydrogels were prepared by combining LIG with poly(ethylene glycol) and poly(methyl vinyl ether-co-maleic acid) through an esterification reaction. The synthesis took place in the solid state and can be accelerated significantly (24 vs 1 h) by the use of microwave (MW) radiation. The prepared hydrogels were characterized by evaluation of their swelling capacities and with the use of infrared spectroscopy/solid-state nuclear magnetic resonance. The prepared hydrogels showed LIG contents ranging between 40% and 24% and water uptake capabilities up to 500%. Furthermore, the hydrophobic nature of LIG facilitated loading of a model hydrophobic drug (curcumin). The hydrogels were capable of sustaining the delivery of this compound for up to 4 days. Finally, the materials demonstrated logarithmic reductions in adherence of Staphylococcus aureus and Proteus mirabilis of up to 5.0 relative to the commonly employed medical material poly(vinyl chloride) (PVC).