Chitosan coating to enhance the therapeutic efficacy of calcium sulfate-based antibiotic therapy in the treatment of chronic osteomyelitis (original) (raw)
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The Thai Journal of Veterinary Medicine, 2013
Three types of gentamicin beads were compared in a rat osteomyelitis model. The gentamicin beads were prepared in cylinder shape (diameter 2 mm x height 4 mm). Gentamicin impregnated polymethylmethacrylate (GI-PMMA) beads were fabricated according to manufacturer's instructions. Gentamicin coated native calcium sulfate (G-NCS) bead and gentamicin coated high porous calcium sulfate (G-HPCS) bead were prepared in laboratory. Osteomyelitis was induced in the rat's tibias by using methicillin resistance Staphylococcus aureus (MRSA). After 3 weeks of infection, the infected tibias were implanted with GI-PMMA bead, G-NCS bead, G-HPCS bead or sham treatment (control). Radiographic change, white blood cell count and infection signs were weekly monitored for 6 weeks. At the end of the experiment, all tibias were collected for histopathologic examination and bone culture. Although white blood cell count and infection signs were not significantly different among different group of rats, the radiolucent area reduced significantly in GI-PMMA, G-NCS and G-HPCS compared to the control group. There was no significant difference in bacterial count among the groups, however, the histopathologic results revealed new bone development in G-NCS and G-HPCS groups, and a large bone defect in GI-PMMA group resulting from bead removal. This study suggests that the G-HPCS can be used as a local antibiotic carrier for management of osteomyelitis instead of calcium sulfate and polymethylmethacrylate beads.
International Journal of Pharmaceutics, 2006
The biodegradable chitosan microspheres containing vancomycin hydrochloride (VANCO) were prepared by spray drying method with different polymer:drug ratios (1:1, 2:1, 3:1 and 4:1). Thermal behaviour, particle size and distribution, morphological characteristics, drug content, encapsulation efficiency, in vitro release assessments of formulations have been carried out to obtain suitable formulation which shows sustained-release effect when implanted. Sterilized VANCO loaded microspheres were implanted to proximal tibia of rats with methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis. Intramuscular (IM) injection of VANCO for 21 days was applied to another group for comparison. After 3 weeks of treatment, bone samples were analysed with a microbiological assay.According to the results, encapsulation efficiency and yield of microspheres in all formulations were higher than 98% and 47%, respectively. Particle sizes of microspheres were smaller than 6 μm. All microsphere formulations have shown sustained-release effect. In vitro drug release rate decreased due to the increase in polymer:drug ratio but no significant difference was seen between these results (p > 0.05). Based on our in vivo data, rats implanted VANCO-loaded chitosan microspheres and administered IM injection showed 3354 ± 3366 and 52500 ± 25635 colony forming unit of MRSA in 1 g bone samples (CFU/g), respectively.As a result, implanted VANCO-loaded microspheres were found to be more effective than IM route for the treatment of experimental osteomyelitis.
Daptomycin Eluted From Calcium Sulfate Appears Effective Against Staphylococcus
Clinical Orthopaedics and Related Research, 2008
The emergence of resistant strains of Grampositive organisms in osteomyelitis creates treatment challenges. Daptomycin is an antibiotic that shows promise for treating some resistant strains of Gram-positive infections; however, it has not been widely used clinically for the treatment of osteomyelitis. We determined whether daptomycin eluted from calcium sulfate-a local delivery vehicle used for the treatment of osteomyelitis-retained activity against Gram-positive bacteria. Daptomycin was mixed with calcium sulfate hemihydrate, with both laboratory powder and a commercial kit, to form a hardened pellet. Daptomycin was eluted from calcium sulfate and retained its ability to inhibit bacterial growth of Staphylococcus aureus and Staphylococcus epidermidis for eluates gathered up to 28 days. Our preliminary data demonstrates sterilized pellets with daptomycin retained their ability to inhibit bacterial growth of certain strains of Gram-positive organisms.
Biodegradable vs non-biodegradable antibiotic delivery devices in the treatment of osteomyelitis
Expert Opinion on Drug Delivery, 2013
Introduction: Chronic osteomyelitis, or bone infection, is a major worldwide cause of morbidity and mortality, as it is exceptionally hard to treat due to patient and pathogen-associated factors. Successful treatment requires surgical debridement together with long-term, high antibiotic concentrations that are best achieved by local delivery devices, either made of degradable or non-degradable materials. Areas covered: Non-degradable delivery devices are frequently constituted by polymethylmethacrylate-based carriers. Drawbacks are the need to remove the carrier (as the carrier itself may provide a substratum for bacterial colonization), inefficient release kinetics and incompatibility with certain antibiotics. These drawbacks have led to the quest for degradable alternatives, but also devices made of biodegradable calcium sulphate, collagen sponges, calcium phosphate or polylactic acids have their specific disadvantages. Expert opinion: Antibiotic treatment of osteomyelitis with the current degradable and non-degradable delivery devices is effective in the majority of cases. Degradable carriers have an advantage over non-degradable carriers that they do not require surgical removal. Synthetic poly(trimethylene carbonate) may be preferred in the future over currently approved lactic/ glycolic acids, because it does not yield acidic degradation products. Moreover, degradable poly(trimethylene carbonate) yields a zero-order release kinetics that may not stimulate development of antibiotic-resistant bacterial strains due to the absence of long-term, low-concentration tail-release.
Fabrication of Chitosan Based Antibacterial Implant for Multibacterial Bone Infection
Journal of Pharmaceutical Research International
Despite advancements in medicines and novel surgical methods, osteomyelitis is still a complex and difficult to treat multi-bacterial bone infection. It generates in tissue necrosis along with rupturing of bone in chronic cases leading towards limited vascularity at infection site, local treatment might not show accountable level of antibiotic at infection site. The present research aims towards development and evaluation of bio-degradable implant of Ciprofloxacin hydrochloride to treat local osteomyelitis. Chitosan is widely investigated biodegradable polymer with hydroxyl moiety which is active and can be altered chemically to develop biomedical and therapeutic dosage forms. Here this active group was modified using epichlorohydrin & crosslinked Chitosan matrices were used as carrier to formulate different Ciprofloxacin implant. In vivo parameters and in vitro study was conducted for optimized batch. The formulation having 40% drug loading (EC4) was found to be optimum when all ev...
EFORT Open Reviews, 2021
Infection in orthopaedic and trauma surgery remains a destructive complication with particularly challenging diagnosis and treatment due to bacterial antibiotic resistance and biofilm formation. Along with surgical debridement and systemic antibiotics, an important type of adjuvant therapy is local antibiotic delivery, with the purpose of eliminating bacterial colonization and biofilm development. Calcium sulphate, as a synthetic absorbable biomaterial used for local antibiotic delivery, has experienced an increasing popularity during the last decade, with multiple promoted advantages such as predictable antibiotic elution kinetics, complete and quick biodegradation, good biocompatibility, and limited associated complications. A series of commercially available antibiotic-delivery systems based on calcium sulphate are under investigation and in clinical use, with different presentations, compositions, and application techniques. The current article presents the main available calciu...
Annals of Clinical Microbiology and Antimicrobials
Background: Osteomyelitis is an acute or chronic inflammatory process of the bone following infection with pyogenic organisms like Staphylococcus aureus. Tobramycin (TOB) is a promising aminoglycoside antibiotic used to treat various bacterial infections, including S. aureus. The aim of this study was to investigate the efficacy of tobramycinloaded calcium phosphate beads (CPB) in a rabbit osteomyelitis model. Methods: Tobramycin (30 mg/mL) was incorporated into CPB by dipping method and the efficacy of TOB-loaded CPB was studied in a rabbit osteomyelitis model. For juxtaposition, CPB with and without TOB were prepared. Twentyfive New Zealand white rabbits were grouped (n = 5) as sham (group 1), TOB-loaded CPB without S. aureus (group 2), S. aureus only (group 3), S. aureus + CPB (group 4), and S. aureus + TOB-loaded CPB (group 5). Groups infected with S. aureus followed by CPB implantation were immediately subjected to surgery at the mid-shaft of the tibia. After 28 days post-surgery, all rabbits were euthanized and the presence or absence of chronic osteomyelitis and the extent of architectural destruction of the bone were assessed by radiology, bacteriology and histological studies. Results: Tobramycin-loaded CPB group potentially inhibited the growth of S. aureus causing 3.2 to 3.4 log 10 reductions in CFU/g of bone tissue compared to the controls. Untreated groups infected with S. aureus showed signs of chronic osteomyelitis with abundant bacterial growth and alterations in bone architecture. The sham group and TOBloaded CPB group showed no evidence of bacterial growth. Conclusions: TOB-incorporated into CPB for local bone administration was proven to be more successful in increasing the efficacy of TOB in this rabbit osteomyelitis model and hence could represent a good alternative to other formulations used in the treatment of osteomyelitis.
Journal of Biomedical Materials Research Part A, 2006
The use of local antibiotics from a biodegradable implant is appealing concept for treatment of chronic osteomyelitis. Our aim was to develop a new drug delivery system based on controlled ciprofloxacin release from poly(d/l-lactide). Cylindrical composite pellets (1.0 ϫ 0.9 mm) were manufactured from bioabsorbable poly(d/l-lactide) matrix and ciprofloxacin (7.4 wt %). In vitro studies were carried out to delineate the release profile of the antibiotic and to verify its antimicrobial activity by means of MIC testing. A long-term study in rabbits was performed to validate the release of ciprofloxacin from the composite in vivo. Therapeutic level of ciprofloxacin (Ͼ2 g/mL) was maintained between 60 and 300 days and the concentration remained below the potentially detrimental level of 20 g/mL in vitro. The released ciprofloxacin had retained its antimicrobial properties against common pathogens. In an exploratory long-term in vivo study with three rabbits, cip-rofloxacin could not be detected from the serum after moderate filling (160 mg) of the tibia (follow-up 168 days), whereas after high dosing (a total dose of 1000 mg in both tibias) ciprofloxacin was found temporarily at low serum concentrations (14-34 ng/mL) during the follow-up of 300 days. The bone concentrations of ciprofloxacin could be measured in all samples at 168 and 300 days. The tested copolylactide matrix seems to be a promising option in selection of resorbable carriers for sustained release of antibiotics, but the composite needs modifications to promote ciprofloxacin release during the first 60 days of implantation.
Effective Treatment of Osteomyelitis with Biodegradable Microspheres in a Rabbit Model
Clinical Orthopaedics & Related Research, 2004
Biodegradable microspheres were manufactured from a high molecular weight copolymer of 50% lactic and 50% glycolic acid and the antibiotic tobramycin. It was hypothesized that the microspheres would be more effective than polymethylmethacrylate beads in the local delivery of tobramycin and that the microspheres would not inhibit bone healing. Osteomyelitis was established in 40 New Zealand White rabbits using Staphylococcus aureus. All animals had irrigation and debridement of the infected radii four weeks after inoculation and were divided into five treatment groups: debridement alone, microspheres alone, microspheres containing tobramycin plus parenteral treatment with cefazolin, polymethylmethacrylate beads containing tobramycin plus parenteral cefazolin, and parenteral cefazolin. All animals were sacrificed after 4 weeks of treatment. The group treated with microspheres plus parenteral antibiotics was the only group to have a significantly higher percentage of animals without bacteria after 4 weeks of treatment when compared with the control group. Additionally, the animals treated with microspheres had a higher degree of bone healing in the defect than the animals treated with bone cement. The most effective treatment was biodegradable microspheres combined with parenteral antibiotic in this rabbit osteomyelitis model.