title: Sustained tobramycin release from polyphosphate double network hydrogels.
abstract: Sustained local delivery of antibiotics from a drug reservoir to treat or prevent bacterial infections can avoid many of the drawbacks of systemic administration of antibiotics. Prolonged local release of high concentrations of antibiotics may also be more effective at treating bacteria in established biofilm populations that are resistant to systemic antibiotics. A double network hydrogel comprising an organic polyphosphate pre-polymer network polymerized within a polyacrylamide network de-swelled to about 50% of its initial volume when the polyphosphate network was crosslinked with polycationic tobramycin, an aminoglycoside antibiotic. The antibiotic-loaded hydrogels contained approximately 200mg/ml of tobramycin. The hydrogels continuously released daily amounts of tobramycin above the Pseudomonas aeruginosa minimal bactericidal concentration for greater than 50days, over the pH range 6.0-8.0, and completely eradicated established P. aeruginosa biofilms within 72h in a flow cell bioreactor. The presence of physiological concentrations of Mg2+and Ca2+ions doubled the cumulative release over 60days. The polyphosphate hydrogels show promise as materials for sustained localized tobramycin delivery to prevent post-operative P. aeruginosa infections including infections established in biofilms.
  
  
  
  Polyphosphate hydrogels were loaded with high concentrations of tobramycin. The hydrogels provided sustained release of bactericidal concentrations of tobramycin for 50days, and were capable of completely eradicating P. aeruginosa in established biofilms. The hydrogels have potential for localized prevention or treatment of P. aeruginosa infections.
authors.affiliation: Department of Bioengineering, University of Utah, 20 S. 2030 East, Salt Lake City, UT 84112, USA.
authors.forename: Dwight D
authors.initials: DD
authors.lastname: Lane
authors.affiliation: Department of Bioengineering, University of Utah, 20 S. 2030 East, Salt Lake City, UT 84112, USA.
authors.forename: Amber K
authors.initials: AK
authors.lastname: Fessler
authors.affiliation: George E. Wahlen Department of Veterans Affairs, Bone and Joint Research Lab, 500 Foothill Dr. (151F), Salt Lake City, UT 84148, USA; Department of Orthopaedics, University of Utah, Salt Lake City, UT, USA.
authors.forename: Seungah
authors.initials: S
authors.lastname: Goo
authors.affiliation: George E. Wahlen Department of Veterans Affairs, Bone and Joint Research Lab, 500 Foothill Dr. (151F), Salt Lake City, UT 84148, USA; Department of Orthopaedics, University of Utah, Salt Lake City, UT, USA; Department of Pathology, University of Utah, Salt Lake City, UT, USA.
authors.forename: Dustin L
authors.initials: DL
authors.lastname: Williams
authors.affiliation: Department of Bioengineering, University of Utah, 20 S. 2030 East, Salt Lake City, UT 84112, USA. Electronic address: russell.stewart@utah.edu.
authors.forename: Russell J
authors.initials: RJ
authors.lastname: Stewart
mesh_terms: D000180:Acrylic Resins / Q000138:chemical synthesis / Q000737:chemistry; D018441:Biofilms / Q000187:drug effects; D019149:Bioreactors; D003692:Delayed-Action Preparations; D065546:Drug Liberation; D020100:Hydrogels / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D008768:Methylmethacrylates / Q000138:chemical synthesis / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D011122:Polyphosphates / Q000737:chemistry*; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D014031:Tobramycin / Q000494:pharmacology*
chemical_list: D000180:Acrylic Resins; D003692:Delayed-Action Preparations; D020100:Hydrogels; D008768:Methylmethacrylates; D011122:Polyphosphates; C006903:carbopol 940; C009931:poly(ethylmethacrylate); D014031:Tobramycin
keywords: Aminoglycoside; Biofilm; Double network hydrogel; Local drug delivery; Polyelectrolyte; Pseudomonas aeruginosa; Sustained release; Tobramycin