Biodegradable Implants Containing Gentamicin: Drug Release and Pharmacokinetics

Firsov, Alexander A.; Nazarov, Alexey D.; Fomina, I P

doi:10.3109/03639048709068686

Cited by 25 publications

(5 citation statements)

References 3 publications

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“…Although there is quick release of gentamicin from its carrier, the bioavailability of gentamicin from collagen fleeces is different from that after intramuscular administration. The release from collagen appears to accelerate in a medium or environment with a rising pH (Firsov 1987). At the surgical site, the pH is lower than physiological pH, suggesting a slower release in vivo than in vitro (Sorensen et al 1990, Blanc 1992.…”

Section: Discussionmentioning

confidence: 95%

In vivo pharmacokinetics of a gentamicin-loaded collagen sponge in acute periprosthetic infection: Serum values in 19 patients

et al. 2008

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Section: Discussionmentioning

confidence: 95%

In vivo pharmacokinetics of a gentamicin-loaded collagen sponge in acute periprosthetic infection: Serum values in 19 patients

et al. 2008

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“…In 1997, Stemberger et al reported about high local levels and low serum antibiotics after implantation of collagen-antibiotic combinations [21]. Comparing the gentamicin pharmacokinetics in the zone of subcutaneous implantation around polymethylmethacrylate beads, Firsov et al observed a three-phase pattern for collagen sponges [22]: [i] An initial high antibiotic peak, which is in accordance with the microbiological demands of high doses for a short time; [ii] after a few h, stabilization of the gentamicin concentration to a practically constant level, above the minimal inhibitory concentration (MIC) of many pathogens for several days; and [iii] finally, the antibiotic level in the tissue diminishes [23]. Comparing the available results due to the extended active agent release out of the granule-collagen-composite, confirmed by the study of Firsov with the accelerated release of the granules, we assume that the collagen part in the composite formulation has a key role for the extended release.…”

Section: Discussionmentioning

confidence: 99%

Release of Antibiotics Out of a Moldable Collagen-β-Tricalciumphosphate-Composite Compared to Two Calcium Phosphate Granules

Roth¹,

Maier

Schmidtmann

et al. 2019

Materials

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Bacterial bone infections after revision surgeries and diseases, like osteomyelitis, are still a challenge with regard to surgical treatments. Local bone infections were treated with antibiotics directly or by controlled drug-releasing scaffolds, like polymethylmethacrylate (PMMA) spheres, which have to be removed at a later stage, but there is a risk of a bacterial contamination during the removement. Therefore, biomaterials loaded with antibiotics for controlled release could be the method of choice: The biomaterials degrade during the drug release, therefore, there is no need for a second surgery to remove the drug eluting agent. Even non-resorbable bone materials are available (e.g., hydroxyapatite (HA)) or resorbable bone graft materials (e.g., beta-tricalcium phosphate (β-TCP)) that will be replaced by newly formed bone. Composite materials with organic additives (e.g., collagen) supports the handling during surgery and enhances the drug loading capacity, as well as the drug releasing time. The purpose of this study was to investigate the loading capacity and the release rate of Vancomycin and Gentamicin on TCP and HA granules in the shape of a degradable scaffold compared to composite materials from TCP mixed with porcine collagen. Its antibacterial efficacy to a more elementary drug with eluting in aqueous solution was examined. The loading capacity of the biomaterials was measured and compared according to the Minimum Inhibition Concentration (MIC) and the Minimum Biofilm Eradication Concentration (MBEC) of a bacterial biofilm after 24 h aging. Antibiotic elution and concentration of gentamycin and vancomycin, as well as inhibition zones, were measured by using the Quantitative Microparticle Systems (QMS) immunoassays. The antibiotic concentration was determined by the automated Beckman Coulter (BC) chemistry device. For examination of the antibacterial activity, inhibition zone diameters were measured. Generally, the antibiotic release is more pronounced during the first couple of days than later. Both TCP granules and HA granules experienced a significantly decline of antibiotics release during the first three days. After the fourth day and beyond, the antibiotic release was below the detection threshold. The antibiotic release of the composite material TCP and porcine collagen declined less drastically and was still in the frame of the specification during the first nine days. There was no significant evidence of interaction effect between antibiotic and material, i.e., the fitted lines for Gentamycin and Vancomycin are almost parallel. During this first in vitro study, β-TCP-Collagen composites shows a significantly higher loading capacity and a steadily release of the antibiotics Gentamycin and Vancomycin, compared to the also used TCP and HA Granules.

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“…However, since PMMA is a non-biodegradable material, secondary surgery is required to remove the beads after gentamicin has been released. Several biodegradable controlled antibiotic-release devices, such as dideoxykanamycin hydroxyapatite/poly(lactic acid) cylinders (Ikada et a1 1985), ampicillin poly(D,L-lactide-co-glycolide) microcapsules (Setterstrom et a1 1991), cefotiam hydroxyapatite beads (Yamamura et al 1992), and gentamicin poly(~lactic acid) microcapsules and cylinders (Sampath et al 1992) have recently been developed (Ikada et a1 1985;Setterstrom et al 1985Setterstrom et al , 1991Firsov et al 1987;Wei et al 1990;Sampath et a1 1992;Shinto et a1 1992;Yamamura et a1 1992;Yu et a1 1992). However, the release properties of these devices were not found to be satisfactory primarily due to poor design and manufacturing.…”

mentioning

confidence: 99%

Biodegradable Controlled Antibiotic Release Devices for Osteomyelitis: Optimization of Release Properties

Zhang

Wyss

Pichora

et al. 1994

Journal of Pharmacy and Pharmacology

172

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Controlled antibiotic release films, melt-extruded cylinders, and suspension-extruded/coated cylinders were manufactured from biodegradable poly(D,L-lactide) (PDLLA) and poly(D,L-lactide-co-epsilon-caprolactone). These devices have potential application in the treatment of osteomyelitis. The in-vitro release properties of the devices were examined with drug loadings varying from 16 to 50%. Gentamicin sulphate films and melt-extruded gentamicin/PDLLA cylinders demonstrated a large initial burst and incomplete release. The films and melt-extruded cylinders made from poly(D,L-lactide-co-epsilon-caprolactone), low mol. wt poly(D,L-lactide), and a mixture of D,L-lactic acid oligomer and high mol. wt poly(D,L-lactide), did not remain intact during the entire release period. While this is undesirable, these materials do have the advantage of not requiring a processing temperature of greater than 110 degrees C. Antibiotic release from high mol. wt PDLLA-coated gentamicin/PDLLA cylinders, with 40 and 50% loading, was very rapid. The antibiotic could only diffuse out through the open ends of the cylinder. Coated gentamicin sulphate cylinders with 20 and 30% drug loading gave the most promising properties in terms of a small initial burst, and a gradual and sustained release. The release rate and duration from the coated cylinders could be adjusted by cutting the cylinder into different lengths; the time required for 90% of the entrapped gentamicin to be released into water from 30% loaded PDLLA-coated cylinders 0.2, 0.4, 0.7 and 1 cm in length was 1000, 1700, 2300, and 2800 h, respectively. This offers a convenient method to adjust the release to meet the specific antibiotic requirement of different patients.(ABSTRACT TRUNCATED AT 250 WORDS)

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Biodegradable Implants Containing Gentamicin: Drug Release and Pharmacokinetics

Cited by 25 publications

References 3 publications

In vivo pharmacokinetics of a gentamicin-loaded collagen sponge in acute periprosthetic infection: Serum values in 19 patients

In vivo pharmacokinetics of a gentamicin-loaded collagen sponge in acute periprosthetic infection: Serum values in 19 patients

Release of Antibiotics Out of a Moldable Collagen-β-Tricalciumphosphate-Composite Compared to Two Calcium Phosphate Granules

Biodegradable Controlled Antibiotic Release Devices for Osteomyelitis: Optimization of Release Properties

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