title: An Infection-Responsive Approach To Reduce Bacterial Adhesion in Urinary Biomaterials.
abstract: Infection is an inevitable consequence of chronic urinary catheterization with associated problems of recurrent catheter encrustation and blockage experienced by approximately 50% of all long-term catheterized patients. In this work, we have exploited, for the first time, the reported pathogen-induced elevation of urine pH as a trigger for "intelligent" antimicrobial release from novel hydrogel drug delivery systems of 2-hydroxyethyl methacrylate and vinyl-functionalized nalidixic acid derivatives, developed as candidate infection-resistant urinary catheter coatings. Demonstrating up to 20-fold faster rates of drug release at pH 10, representing infected urine pH, than at pH 7 and achieving reductions of up to 96.5% in in vitro bacterial adherence, our paradigm of pH-responsive drug delivery, which requires no external manipulation, therefore represents a promising development toward the prevention of catheter-associated urinary tract infections in vivo.
authors.affiliation: School of Pharmacy, Queen's University Belfast , 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, United Kingdom.
authors.forename: Colin P
authors.initials: CP
authors.lastname: McCoy
authors.affiliation: School of Pharmacy, Queen's University Belfast , 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, United Kingdom.
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Irwin
authors.affiliation: School of Pharmacy, Queen's University Belfast , 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, United Kingdom.
authors.forename: Christopher
authors.initials: C
authors.lastname: Brady
authors.affiliation: School of Pharmacy, Queen's University Belfast , 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, United Kingdom.
authors.forename: David S
authors.initials: DS
authors.lastname: Jones
authors.affiliation: School of Pharmacy, Queen's University Belfast , 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, United Kingdom.
authors.forename: Louise
authors.initials: L
authors.lastname: Carson
authors.affiliation: School of Pharmacy, Queen's University Belfast , 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, United Kingdom.
authors.forename: Gavin P
authors.initials: GP
authors.lastname: Andrews
authors.affiliation: School of Pharmacy, Queen's University Belfast , 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, United Kingdom.
authors.forename: Sean P
authors.initials: SP
authors.lastname: Gorman
mesh_terms: D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology; D001422:Bacterial Adhesion / Q000187:drug effects*; D001672:Biocompatible Materials / Q000737:chemistry* / Q000494:pharmacology; D018441:Biofilms / Q000187:drug effects; D055499:Catheter-Related Infections / Q000517:prevention & control; D008689:Methacrylates / Q000737:chemistry*; D009268:Nalidixic Acid / Q000737:chemistry / Q000494:pharmacology; D014552:Urinary Tract Infections / Q000517:prevention & control
chemical_list: D000890:Anti-Infective Agents; D001672:Biocompatible Materials; D008689:Methacrylates; D009268:Nalidixic Acid; C005044:hydroxyethyl methacrylate
keywords: drug conjugate copolymer; ester hydrolysis; pH-responsive; urinary catheter infection