Journal
PHARMACEUTICAL RESEARCH
Volume 34, Issue 10, Pages 2075-2083Publisher
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11095-017-2212-5
Keywords
alginate; gellan gum; gentamicin; local drug delivery; membranes
Funding
- National Science Centre, Poland [012/05/B/ST8/00129]
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To develop polysaccharide-based membranes that allow controlled and localized delivery of gentamicin for the treatment of post-operative bone infections. 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. 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. GUM + Ca membrane holds promise for effective treatment of bone infections thanks to favorable pharmacokinetics, bactericidal activity, cytocompatibility and good mechanical properties.
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