Novel fatty acid gentamicin salts as slow-release drug carrier systems for anti-infective protection of vascular biomaterials

Obermeier, Andreas; Matl, F. D.; Schwabe, J.W.R.; Zimmermann, Alexander; Kühn, Klaus-Dieter; Lakemeier, Stefan; Eisenhart-Rothe, Rüdiger von; Stemberger, A.; Burgkart, Rainer

doi:10.1007/s10856-012-4631-5

Cited by 15 publications

(11 citation statements)

References 15 publications

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“…Neutralization with sodium hydroxide results in SDS. Gentamicin-SDS was used in an in vitro-study before [19,20] and showed promising results in vascular biomaterials [25]. We employed this combination as an effective treatment control (Group C).…”

Section: Discussionmentioning

confidence: 99%

Gentamicin coating of plasma chemical oxidized titanium alloy prevents implant-related osteomyelitis in rats

et al. 2016

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Section: Discussionmentioning

confidence: 99%

Gentamicin coating of plasma chemical oxidized titanium alloy prevents implant-related osteomyelitis in rats

et al. 2016

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“…Tripalmitin was added to slow the release of the antibiotics gentamicin and vancomycin. The use of fatty acids to influence release kinetics had previously been documented (24)(25)(26).…”

Section: Discussionmentioning

confidence: 99%

Antimicrobial Formulations of Absorbable Bone Substitute Materials as Drug Carriers Based on Calcium Sulfate

Pförringer

Obermeier

Kiokekli

et al. 2016

Antimicrob Agents Chemother

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c Substitution of bones is a well-established, necessary procedure to treat bone defects in trauma and orthopedic surgeries. For prevention or treatment of perioperative infection, the implantation of resorbable bone substitute materials carrying antibiotics is a necessary treatment. In this study, we investigated the newly formulated calcium-based resorbable bone substitute materials containing either gentamicin (CaSO 4 -G [Herafill-G]), vancomycin (CaSO 4 -V), or tobramycin (Osteoset). We characterized the released antibiotic concentration per unit. Bone substitute materials were implanted in bones of rabbits via a standardized surgical procedure. Clinical parameters and levels of the antibiotic-releasing materials in serum were determined. Local concentrations of antibiotics were measured using antimicrobial tests of bone tissue. Aminoglycoside release kinetics in vitro per square millimeter of bead surface showed the most prolonged release for gentamicin, followed by vancomycin and, with the fastest release, tobramycin. In vivo level in serum detected over 28 days was highest for gentamicin at 0.42 g/ml, followed by vancomycin at 0.11 g/ml and tobramycin at 0.04 g/ml. The clinical parameters indicated high biocompatibility for materials used. None of the rabbits subjected to the procedure showed any adverse reaction. The highest availability of antibiotics at 14.8 g/g on day 1 in the cortical tibia ex vivo was demonstrated for gentamicin, decreasing within 14 days. In the medulla, vancomycin showed a high level at 444 g/g on day 1, decreasing continuously over 14 days, whereas gentamicin decreased faster within the initial 3 days. The compared antibiotic formulations varied significantly in release kinetics in serum as well as locally in medulla and cortex.

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“…Fatty acids constitute a lubricating film and are state of the art in order to reduce the unwanted sewing effect of sutures. This kind of drug-release system still allows slow-release properties, because of low solubility of fatty acid carriers in aqueous environments [37], [38].…”

Section: Discussionmentioning

confidence: 99%

Novel High Efficient Coatings for Anti-Microbial Surgical Sutures Using Chlorhexidine in Fatty Acid Slow-Release Carrier Systems

et al. 2014

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Sutures can cause challenging surgical site infections, due to capillary effects resulting in bacteria permeating wounds. Anti-microbial sutures may avoid these complications by inhibiting bacterial pathogens. Recently, first triclosan-resistances were reported and therefore alternative substances are becoming clinically relevant. As triclosan alternative chlorhexidine, the “gold standard” in oral antiseptics was used. The aim of the study was to optimize novel slow release chlorhexidine coatings based on fatty acids in surgical sutures, to reach a high anti-microbial efficacy and simultaneously high biocompatibility. Sutures were coated with chlorhexidine laurate and chlorhexidine palmitate solutions leading to 11, 22 or 33 µg/cm drug concentration per length. Drug release profiles were determined in aqueous elutions. Antibacterial efficacy against Staphylococcus aureus was assessed in agar diffusion tests. Biocompatibility was evaluated via established cytotoxicity assay (WST-1). A commercially triclosan-containing suture (Vicryl Plus), was used as anti-microbial reference. All coated sutures fulfilled European Pharmacopoeia required tensile strength and proved continuous slow drug release over 96 hours without complete wash out of the coated drug. High anti-microbial efficacy for up to 5 days was observed. Regarding biocompatibility, sutures using 11 µg/cm drug content displayed acceptable cytotoxic levels according to ISO 10993-5. The highest potential for human application were shown by the 11 µg/cm chlorhexidine coated sutures with palmitic acid. These novel coated sutures might be alternatives to already established anti-microbial sutures such as Vicryl Plus in case of triclosan-resistance. Chlorhexidine is already an established oral antiseptic, safety and efficacy should be proven for clinical applications in anti-microbial sutures.

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Novel fatty acid gentamicin salts as slow-release drug carrier systems for anti-infective protection of vascular biomaterials

Cited by 15 publications

References 15 publications

Gentamicin coating of plasma chemical oxidized titanium alloy prevents implant-related osteomyelitis in rats

Gentamicin coating of plasma chemical oxidized titanium alloy prevents implant-related osteomyelitis in rats

Antimicrobial Formulations of Absorbable Bone Substitute Materials as Drug Carriers Based on Calcium Sulfate

Novel High Efficient Coatings for Anti-Microbial Surgical Sutures Using Chlorhexidine in Fatty Acid Slow-Release Carrier Systems

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