title: Infection-responsive drug delivery from urinary biomaterials controlled by a novel kinetic and thermodynamic approach.
abstract: OBJECTIVE
  The 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.
  
  
  METHODS
  p(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.
  
  
  RESULTS
  The 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.
  
  
  CONCLUSIONS
  The 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.
authors.affiliation: School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7BL, Northern Ireland, UK.
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Irwin
authors.forename: Colin P
authors.initials: CP
authors.lastname: McCoy
authors.forename: David S
authors.initials: DS
authors.lastname: Jones
authors.forename: Sean P
authors.initials: SP
authors.lastname: Gorman
mesh_terms: D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000494:pharmacology; D001672:Biocompatible Materials / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000737:chemistry*; D006801:Humans; D020100:Hydrogels / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D008689:Methacrylates / Q000737:chemistry*; D009268:Nalidixic Acid / Q000008:administration & dosage* / Q000494:pharmacology; D011512:Proteus Infections / Q000188:drug therapy; D011513:Proteus mirabilis / Q000187:drug effects; D013816:Thermodynamics
chemical_list: D000890:Anti-Infective Agents; D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D020100:Hydrogels; D008689:Methacrylates; D009268:Nalidixic Acid; C005044:hydroxyethyl methacrylate