A novel drug delivery system for osteomyelitis using porous hydroxyapatite blocks loaded by centrifugation

Itokazu, Mansho; Matsunaga, Takanobu; Kumazawa, Shinji; Yang, Weizhong

doi:10.1002/jab.770060304

Cited by 42 publications

(30 citation statements)

References 8 publications

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“…3,5,7,10,34,[39][40][41][42][43][44][45] We chose a powderpowder mixture here followed by compression to allow incorporation of the TA into the matrix core. Two techniques are proposed: dynamic compaction and isostatic compression.…”

Section: Discussionmentioning

confidence: 99%

Influence of isostatic compression on the stability of vancomycin loaded with a calcium phosphate-implantable drug delivery device

Gautier

Caillon²,

Ray

et al. 2000

J. Biomed. Mater. Res.

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It is essential to prevent microbial infections after osteoarticular trauma or prosthesis implantation. As an alternative to antibiotic parenteral administration, antibiotic-loaded biomaterials allow high concentrations to be obtained in situ without systemic toxicity. Although the formulation of biphasic calcium-phosphate (BCP)-vancomycin granules by isostatic compression has recently been used to produce drug-delivery devices, the stability of vancomycin needs to be proven. In this study, vancomycin was associated with BCP powders by isostatic compression at 100, 140, or 200 MPa and then extracted or released by a rotating paddle system for 24 h. Vancomycin assays were performed by spectrophotometric and microbiological methods. The results show that all vancomycin associated with the material was recovered after extraction without degradation. Thus, vancomycin was not denaturated after application of 100, 140, or 200 MPa of isostatic compression. The results for vancomycin released from granules compressed at the three pressures were not significantly different (p =.01) whether assays were performed microbiologically or spectrophotometrically, indicating a good correlation between the two methods. This process involving high pressure appears to be a good means of developing drug delivery devices loaded with therapeutic agents without denaturating the components.

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Section: Discussionmentioning

confidence: 99%

Influence of isostatic compression on the stability of vancomycin loaded with a calcium phosphate-implantable drug delivery device

Gautier

Caillon²,

Ray

et al. 2000

J. Biomed. Mater. Res.

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“…The severe impact of antibiotic-resistant infections has led to the search for new and more efficient therapeutic applications [19,34,36,38]. Some of these methods include using pharmacodynamic synergism between two drugs against bacterial species.…”

Section: Discussionmentioning

confidence: 99%

Chitosan Sponges for Local Synergistic Infection Therapy: A Pilot Study

Smith

Moshref

Jennings

et al. 2013

Clinical Orthopaedics &Amp; Related Research

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Background Although bacterial antibiotic resistance is increasing, fewer new antibiotics are being developed to compensate. Localized delivery of synergistic antiseptics and antibiotics with a chitosan sponge device may offer an alternative infection treatment. Questions/purposes In this pilot study, we asked whether antiseptic and antibiotic combinations provided in vitro synergism against Staphylococcus aureus, whether synergism reduces cell viability, and whether their combination releases drugs at inhibitory levels. Methods To investigate the pharmacodynamics among three combinations of the antiseptic chlorhexidine digluconate (CHX) with the antibiotics amikacin, daptomycin, and vancomycin (VAN) (n = 1), we determined the fractional inhibitory concentration (FIC) index against S aureus Cowan I. The determined synergistic combination of CHX and VAN was evaluated for cell compatibility using NIH/3T3 fibroblasts (n = 3) and the drug release profile from a chitosan sponge device (n = 5). Results With an FIC index \ 0.5, the combination of CHX + VAN exhibited synergism against S aureus. CHX concentrations C 3.91 lg/mL resulted in fibroblast viability decrease, whereas the combination of CHX + VAN did not decrease fibroblast viability until their concentrations reached C 7.81 lg/mL. The CHX and VAN release profile, both individually and in combination, was an initial bolus with no difference between eluate concentrations after Day 5. Conclusions CHX + VAN combination may be delivered locally by a chitosan sponge that synergistically inhibits S aureus growth. Clinical Relevance The use of synergism between combined antibiotic and antiseptics delivered at high local concentrations with an implanted chitosan sponge may provide a useful alternative infection treatment option.

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“…However, one problem inherent in the local insertion of a compound is the disadvantage of requiring subsequent surgery for replacement with an autograft. In recent studies, hydroxyapatite ceramics [8,[14][15][16] or fibrin glue were developed as an advanced antibiotic carrier system. However, one of the disadvantages with the latter is the quick release, because the wide-mesh fibrin matrix cannot hinder the diffusion of the antibiotics and prolonged clotting time of fibrin-antibiotic compound.…”

Section: Bacteriological Assessmentmentioning

confidence: 99%

The sustained release of antibiotic from freeze-dried fibrin-antibiotic compound and efficacies in a rat model of osteomyelitis

et al. 1997

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The kinetics of drug release from fibrin adhesive agent (consisting of fibrinogen, factor 8, thrombin, aportinin and calcium chloride)-antibiotic compound and efficacy on rat experimental osteomyelitis were studied. To enhance the slow release activities of antibiotic, a mixture of fibrin clots was freeze-dried. Effects of freeze-drying were to make a fibrin clot an interlinked pore and to increase crosslinking rate containing an antibiotic. A diffusion test from aminoglycoside (Arbekacin Sulfate: 200 mg) compound was carried out. In vitro study freeze-dried antibiotic compound (FFAC: 1 cm3) was placed in saline (3 ml). The saline was replaced every 48 h and the previous solution was stored at -45 degrees C until assay. The result was that a concentration of 0.4 mg/l, sufficiently high to control Staphylococcus aureus strain IM2-42, was maintained within nine exchanges of saline after 18 days. In vivo animal experiments, FFAC (2 x 2 x 3 mm) were tested in rats with established Staphylococcus aureus osteomyelitis in the proximal tibia. The animals were observed for radiographic signs of infection and tissue was examined histopathologically. Bacterial counts by bone cultures were statistically lower in rats implanted with FFAC than in those only given a drug-free FFC and curettage. Radiographical and histological observations also showed beneficial effects of the FFAC. The results suggest that the FFAC provide a simple drug delivery system, and may be a promising alternative treatment for osteomyelitis.

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A novel drug delivery system for osteomyelitis using porous hydroxyapatite blocks loaded by centrifugation

Cited by 42 publications

References 8 publications

Influence of isostatic compression on the stability of vancomycin loaded with a calcium phosphate-implantable drug delivery device

Influence of isostatic compression on the stability of vancomycin loaded with a calcium phosphate-implantable drug delivery device

Chitosan Sponges for Local Synergistic Infection Therapy: A Pilot Study

The sustained release of antibiotic from freeze-dried fibrin-antibiotic compound and efficacies in a rat model of osteomyelitis

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