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Characterization and Antibiofilm Activity of Mannitol–Chitosan-Blended Paste for Local Antibiotic Delivery System

Department of Biomedical Engineering, Herff College of Engineering, University of Memphis, Memphis, TN 38152, USA
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Author to whom correspondence should be addressed.
Mar. Drugs 2019, 17(9), 517; https://doi.org/10.3390/md17090517
Received: 21 June 2019 / Revised: 23 August 2019 / Accepted: 28 August 2019 / Published: 2 September 2019
(This article belongs to the Special Issue Biofilm Inhibitors of Marine Origin)
Mannitol, a polyalcohol bacterial metabolite, has been shown to activate dormant persister cells within bacterial biofilm. This study sought to evaluate an injectable blend of mannitol, chitosan, and polyethylene glycol for delivery of antibiotics and mannitol for eradication of Staphylococcal biofilm. Mannitol blends were injectable and had decreased dissociation and degradation in the enzyme lysozyme compared to blends without mannitol. Vancomycin and amikacin eluted in a burst response, with active concentrations extended to seven days compared to five days for blends without mannitol. Mannitol eluted from the paste in a burst the first day and continued through Day 4. Eluates from the mannitol pastes with and without antibiotics decreased viability of established S. aureus biofilm by up to 95.5% compared to blends without mannitol, which only decreased biofilm when loaded with antibiotics. Cytocompatibility tests indicated no adverse effects on viability of fibroblasts. In vivo evaluation of inflammatory response revealed mannitol blends scored within the 2–4 range at Week 1 (2.6 ± 1.1) and at Week 4 (3.0 ± 0.8), indicative of moderate inflammation and comparable to non-mannitol pastes (p = 0.065). Clinically, this paste could be loaded with clinician-selected antibiotics and used as an adjunctive therapy for musculoskeletal infection prevention and treatment. View Full-Text
Keywords: biofilm; chitosan; biomaterial; local drug delivery; persister; Staphylococcus; infection; mannitol; implant biofilm; chitosan; biomaterial; local drug delivery; persister; Staphylococcus; infection; mannitol; implant
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Pace, L.R.; Harrison, Z.L.; Brown, M.N.; Haggard, W.O.; Jennings, J.A. Characterization and Antibiofilm Activity of Mannitol–Chitosan-Blended Paste for Local Antibiotic Delivery System. Mar. Drugs 2019, 17, 517.

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