Urszula Cibor1, Małgorzata Krok-Borkowicz1, Monika Brzychczy-Włoch2, Łucja Rumian1, Krzysztof Pietryga1, Dominika Kulig1, Wojciech Chrzanowski3,4, Elżbieta Pamuła5. 1. Department of Biomaterials, AGH University of Science and Technology, Faculty of Materials Science and Ceramics, al. A. Mickiewicza 30, 30-059, Kraków, Poland. 2. Department of Microbiology, Jagiellonian University, Medical College, ul. Czysta 18, 31-121, Kraków, Poland. 3. Faculty of Pharmacy, The University of Sydney, Sydney, NSW, 2006, Australia. 4. The Australian Institute of Nanoscale Science and Technology, University of Sydney, Sydney, NSW, 2006, Australia. 5. Department of Biomaterials, AGH University of Science and Technology, Faculty of Materials Science and Ceramics, al. A. Mickiewicza 30, 30-059, Kraków, Poland. epamula@agh.edu.pl.
Abstract
PURPOSE: To develop polysaccharide-based membranes that allow controlled and localized delivery of gentamicin for the treatment of post-operative bone infections. METHODS: Membranes made of gellan gum (GUM), sodium alginate (ALG), GUM and ALG crosslinked with calcium ions (GUM + Ca and ALG + Ca, respectively) as well as reference collagen (COL) were produced by freeze-drying. Mechanical properties, drug release, antimicrobial activity and cytocompatibility of the membranes were assessed. RESULTS: The most appropriate handling and mechanical properties (Young's modulus, E = 92 ± 4 MPa and breaking force, F MAX = 2.6 ± 0.1 N) had GUM + Ca membrane. In contrast, COL membrane showed F MAX = 0.14 ± 0.02 N, E = 1.0 ± 0.3 MPa and was deemed to be unsuitable for antibiotic delivery. The pharmacokinetic data demonstrated a uniform and sustainable delivery of gentamicin from GUM + Ca (44.4 ± 1.3% within 3 weeks), while for COL, ALG and ALG + Ca membranes the most of the drug was released within 24 h (55.3 ± 1.9%, 52.5 ± 1.5% and 37.5 ± 1.8%, respectively). Antimicrobial activity against S. aureus and S. epidermidis was confirmed for all the membranes. GUM + Ca and COL membranes supported osteoblasts growth, whereas on ALG and ALG + Ca membranes cell growth was reduced. CONCLUSIONS: GUM + Ca membrane holds promise for effective treatment of bone infections thanks to favorable pharmacokinetics, bactericidal activity, cytocompatibility and good mechanical properties.
PURPOSE: To develop polysaccharide-based membranes that allow controlled and localized delivery of gentamicin for the treatment of post-operative bone infections. METHODS: Membranes made of gellan gum (GUM), sodium alginate (ALG), GUM and ALG crosslinked with calcium ions (GUM + Ca and ALG + Ca, respectively) as well as reference collagen (COL) were produced by freeze-drying. Mechanical properties, drug release, antimicrobial activity and cytocompatibility of the membranes were assessed. RESULTS: The most appropriate handling and mechanical properties (Young's modulus, E = 92 ± 4 MPa and breaking force, F MAX = 2.6 ± 0.1 N) had GUM + Ca membrane. In contrast, COL membrane showed F MAX = 0.14 ± 0.02 N, E = 1.0 ± 0.3 MPa and was deemed to be unsuitable for antibiotic delivery. The pharmacokinetic data demonstrated a uniform and sustainable delivery of gentamicin from GUM + Ca (44.4 ± 1.3% within 3 weeks), while for COL, ALG and ALG + Ca membranes the most of the drug was released within 24 h (55.3 ± 1.9%, 52.5 ± 1.5% and 37.5 ± 1.8%, respectively). Antimicrobial activity against S. aureus and S. epidermidis was confirmed for all the membranes. GUM + Ca and COL membranes supported osteoblasts growth, whereas on ALG and ALG + Ca membranes cell growth was reduced. CONCLUSIONS: GUM + Ca membrane holds promise for effective treatment of bone infections thanks to favorable pharmacokinetics, bactericidal activity, cytocompatibility and good mechanical properties.
Entities:
Keywords:
alginate; gellan gum; gentamicin; local drug delivery; membranes
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