Gentamicin-Loaded Polysaccharide Membranes for Prevention and Treatment of Post-operative Wound Infections in the Skeletal System

• Published in: Pharmaceutical research Vol. 34; no. 10; pp. 2075 - 2083
• Main Authors: Cibor, Urszula, Krok-Borkowicz, Małgorzata, Brzychczy-Włoch, Monika, Rumian, Łucja, Pietryga, Krzysztof, Kulig, Dominika, Chrzanowski, Wojciech, Pamuła, Elżbieta
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.10.2017; Springer; Springer Nature B.V
• Subjects: Alginates - chemistry; Alginic acid; Aminoglycosides; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antibiotics; Antimicrobial activity; Antimicrobial agents; Bactericidal activity; Biochemistry; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Calcium; Calcium - chemistry; Calcium ions; Collagen; Collagen - chemistry; Cross-Linking Reagents - chemistry; Drug Carriers - chemistry; Drug Liberation; Freeze drying; Gellan gum; Gentamicin; Gentamicins - administration & dosage; Gentamicins - chemistry; Gentamicins - pharmacology; Glucuronic Acid - chemistry; Health aspects; Hexuronic Acids - chemistry; Humans; Infections; Materials Testing - methods; Mechanical properties; Medical Law; Membranes; Membranes, Artificial; Modulus of elasticity; Osteoblasts; Osteomyelitis - drug therapy; Osteomyelitis - prevention & control; Pharmacokinetics; Pharmacology/Toxicology; Pharmacy; Polysaccharides; Polysaccharides - chemistry; Polysaccharides, Bacterial - chemistry; Research Paper; Skeletal system; Sodium; Sodium alginate; Staphylococcus aureus - drug effects; Wound Infection - drug therapy; Wound Infection - prevention & control; Wounds; alginate; membranes; gentamicin; gellan gum; local drug delivery
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-017-2212-5

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.