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

Abstract

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.

Fibrin matrices: The versatile therapeutic delivery systems

“…Transforming Growth Factor β1 [10,11] Platelet-Derived Growth Factors (PDGF-BB, AB) [12,13] Insuline Like Growth Factor (IGF-1) [12] Interleukin-1β [14] Epidermal Growth Factor (EGF) [15] Enzymes/proenzymes Plasminogen [16] Tissue Plasminogen Activator (tPA) [16] Plasminogen Activator Inhibitor [17] Thrombin [18] Neomycin, Gentamicin, Polymyxin E in vitro [81] Cephalotin in vitro and in vivo [82] Cefotaxime in vivo [83] Metranidazole, Bacitracine in vivo [84] Cefoxitin, Gentamicin in vivo [85] Tobramycin in vitro and in vivo [86] Gentamicin derivative in vitro and in vivo [87] Ceftazydime,Tobramycin, Gentamicin,Clindamycin, Ampicillin in vitro [88] Teicoplanin,Ciproflaxacin, Cefoxitin, Gentamicin in vitro [89] Gentamycin derivative in vitro and in vivo [90] Clindamycin, Cefotaxime in vivo [91] Sisomicin in vivo [92] Neomycine in vivo [93] Cifroflaxacin in vitro and in vivo [94] Ampicillin, Debakacin, Gentamicin, Carbenicillin, Ceftazidin, Cefoxitin, Cefoxitin, Polymixin B, Mupirocin, Norflaxacin,Clindamycin,Nitrofurazone in vitro [95] Oflaxacin, Ampicillin, Gentamicin in vitro [96] Abrekacin sulfate in vitro and in vivo [97] Vancomycin, Cephalothin, Gentamicin, Teicoplanin in vitro and in vivo [98] Tetracyclin in vivo [58] Tetracyclin in vitro and in vivo [31] Tetracyclin in vitro [36] Ceftazidime, Moxifloxacin, Lomefloxacin,Vancomycin in vivo [99] Vancomycin in vivo [100] …”

Novel interpenetrating network microspheres of xanthan gum–poly(vinyl alcohol) for the delivery of diclofenac sodium to the intestine—in vitro and in vivo evaluation

“…In recent years, considerable attention has been focused on hydrophilic polymers in the design of oral controlled drug delivery systems because of their flexibility to obtain a desirable drug release profile, cost effectiveness, and broad regulatory acceptance (Al-Saidan et al, 2005). These polymeric systems have been the potential candidates to deliver bioactive molecules, particularly in controlled release applications (Itokazu et al, 1997;Kawaguchi, 2000). Such naturally abundant carbohydrate polymers, though exhibiting some limitations in their reactivity and processibility, have still been used after being modified by crosslinking, blending, etc.…”

Heparinized nanohydroxyapatite/collagen granules for controlled release of vancomycin

“…23,24 Moreover, the size of the granules is also adequate to perform in vivo studies using an osteomyelitis rat model. 25 SEM images revealed the presence of interconnective macroporosity, which is desirable for bone tissue regeneration, as interconnectivity allows cell migration, neovascularization, and transport of nutrients and proteins. In addition, the presence of macroporosity induces osteoinduction.…”