Nanoporous delivery system to treat osteomyelitis and regenerate bone: Gentamicin release kinetics and bactericidal effect (original) (raw)
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ACS Applied Bio Materials
Antibiotic laden bone cements are regularly employed to prevent infections after joint replacement surgeries. We have developed silica nanocarriers loaded with gentamicin as a drug delivery systems to be dispersed in Poly-methyl-methacrylate (PMMA) bone cement for controlling and extending the release of the antibiotic from bone cements, thus proving a prolonged antimicrobial activity,. Layerby-Layer self-assembly was used to deposit gentamicin between alginate layers and two different Poly-beta-amino esters on the silica nanoparticles. The release of gentamicin from PMMA bone cement containing silica nanocarriers continued for about 30 days compared to 6 days when the same amount of antibiotic was added as pure powder (as in commercial formulations); moreover the media containing the released antimicrobial drug was capable of preventing the growth of numerous bacteria species responsible for prosthetic joint infections (both catalogue strains and clinical isolates) for longer periods of time than in case of commercial formulation; thus confirming the extended antimicrobial properties of the drug once released from the carrier. No detrimental effects toward human osteoblasts were also observed; moreover bone cement material characteristics such as curing time, water uptake and mechanical properties were unaffected when the silica nanocarriers were added. 6 Supporting information Generalised linear models, fitting results (coefficients, plots, residues), gentamicin MIC of the bacterial species employed.
Silica-Polymer Composites as the Novel Antibiotic Delivery Systems for Bone Tissue Infection
Pharmaceutics, 2019
Bone tissue inflammation, osteomyelitis, is commonly caused by bacterial invasion and requires prolonged antibiotic therapy for weeks or months. Thus, the aim of this study was to develop novel silica-polymer local bone antibiotic delivery systems characterized by a sustained release of ciprofloxacin (CIP) which remain active against Staphylococcus aureus for a few weeks, and do not have a toxic effect towards human osteoblasts. Four formulations composed of ethylcellulose (EC), polydimethylsiloxane (PDMS), freeze-dried CIP, and CIP-adsorbed mesoporous silica materials (MCM-41-CIP) were prepared via solvent-evaporation blending method. All obtained composites were characterized in terms of molecular structure, morphological, and structural properties by using Fourier Transform Infrared Spectroscopy (FTIR), scanning electron microscopy equipped with energy-dispersive X-ray spectroscopy (SEM/EDX), and X-ray diffraction (XRD), thermal stability by thermogravimetric analysis (TGA) and d...
Resorbable bioactive ceramic for treatment of bone infection
Journal of Biomedical Materials Research Part A, 2010
Polymethylmethacrylate (PMMA) beads have been widely used in the treatment of bone infection over the last three decades. Although PMMA does offer a mechanism to quickly and effectively administer a localized dose of antibiotic to the site of infection, its efficacy is limited by its nonresorbability and nonbioactivity. Resorbable bioactive silica-calcium phosphate nanocomposite (SCPC75) was investigated as a novel controlled release carrier of vancomycin for the treatment of osteomyelitis. SCPC75 particles adsorbed significantly higher amount of vancomycin compared with PMMA. Moreover, SCPC75 provided a sustained release kinetics of therapeutic dose of vancomycin up to 35 days. The novel resorbable ceramic was able to release 95.5% of the adsorbed drug in an average dose of 12 lg/mL/day over 480 h (35 days). In conjunction with the sustained drug release, a controlled dissolution rate that led to 40% mass loss of SCPC75 was observed. On the other hand, PMMA provided a sustained release of a therapeutic dose of vancomycin for 14 days after which minimal concentration of the drug was detected. Moreover, PMMA retained 32% of the drug adsorbed onto its surface. The SCPC-vancomycin implant can serve a dual function: provide a sustained therapeutic dose of antibiotic to eradicate infection and stimulate bone cell differentiation and new bone formation. 2010 Wiley Periodicals, Inc.
A New Type of Biphasic Calcium Phosphate Cement as a Gentamicin Carrier for Osteomyelitis
Evidence-Based Complementary and Alternative Medicine, 2013
Osteomyelitis therapy is a long-term and inconvenient procedure for a patient. Antibiotic-loaded bone cements are both a complementary and alternative treatment option to intravenous antibiotic therapy for the treatment of osteomyelitis. In the current study, the biphasic calcium phosphate cement (CPC), calledα-TCP/HAP (α-tricalcium phosphate/hydroxyapatite) biphasic cement, was prepared as an antibiotics carrier for osteomyelitis. The developed biphasic cement with a microstructure ofα-TCP surrounding the HAP has a fast setting time which will fulfill the clinical demand. The X-ray diffraction and Fourier transform infrared spectrometry analyses showed the final phase to be HAP, the basic bone mineral, after setting for a period of time. Scanning electron microscopy revealed a porous structure with particle sizes of a few micrometers. The addition of gentamicin inα-TCP/HAP would delay the transition ofα-TCP but would not change the final-phase HAP. The gentamicin-loadedα-TCP/HAP su...
Advances in Applied Ceramics, 2011
In this present research, calcium phosphate cement (CPC) paste was prepared by combining cement liquids comprised of 4 wt-% disodium hydrogen orthophosphate with cement powders that consisted of b-tricalcium phosphate and monocalcium phosphate monohydrate. In the in vitro study, the release of gentamicin sulphate (GS) from standard cylindrical samples of the prepared CPC immersion in phosphate buffered saline solution was measured by high performance liquid chromatography test over a period of time. In addition, as a representative for biomedical properties, setting time, injectability and compressive strength were measured in order to detect changes when mixing CPC with GS. In addition, the pH values of the phosphate buffered saline solution containing samples descended gradually until reaching equilibrium pH. Overall, the results from in vitro release study showed that it reached its maximum level, which was 35% of the initial value of the GS on day 15, suggesting no irreversible binding occurred between the cement paste and the antibiotic.
International Journal of Molecular Sciences
A gentamicin-loaded hydroxyapatite/collagen bone-like nanocomposite (GNT-HAp/Col) was fabricated and evaluated for its absorption–desorption properties, antibacterial efficacy, and cytotoxicity. The hydroxyapatite/collagen bone-like nanocomposite (HAp/Col) powder was mixed with gentamicin sulfate (GNT) in phosphate-buffered saline (PBS) at room temperature. After 6 h mixing, the GNT adsorption in all conditions reached plateau by Langmuir’s isotherm, and maximum GNT adsorption amount was 34 ± 7 μg in 250 μg/mL GNT solution. Saturated GNT-loaded HAp/Col powder of 100 mg was soaked in 10 mL of PBS at 37 °C and released all GNT in 3 days. A shaking culture method for a GNT extraction from the GNT-HAp/Col and an inhibition zone assay for the GNT-HAp/Col compact showed antibacterial efficacy to Escherichia coli (E. coli) at least for 2 days. From the release profile of the GNT from the GNT-HAp/Col powder, antibacterial efficacy would affect E. coli at least for 3 days. Further, no cytoto...
Ceramics …, 2010
A calcium phosphate cement containing an antibiotic can be used for filling bone defects and to ensure local antibiotherapy. Therefore, in the present research, cement paste were prepared by combining cement liquids comprised of 4 wt.% Na2HPO4 with cement powders that consisted of β-tricalcium phosphate (β-TCP) and monocalcium phosphate monohydrate (MCPM). Gentamicin sulfate was also loaded on the cements and its in vitro release was evaluated over a period of time. The cement setting times were compared before and after drug addition. According to results, the initial and final setting times of samples came down after drug addition, reached to 5 and 15 min, respectively. Compressive strength of the drug-loaded samples aged in PBS measured about 30-40 MPa and showed it did not vary significantly with the period of aging until 36 days (p<0.05). pH values of the PBS solution containing samples descended gradually until reached to an equilibrium pH. Phase analysis of the samples with X-ray analysis (XRD) indicated the presence of monetite and β-TCP in all samples. Microstructure of the fracture surface showed that the cement particles tended to form a highly integrated microporous structure. Extrusion curves of cement paste indicating that it can be delivered through a surgical gun in small non-load bearing bone defects. Finally, the results showed it reached its maximum level (35% of the initial value of the drug) on day 15, suggesting no irreversible binding occurred between the cement paste and the antibiotic of Gentamicin sulfate.
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...
Ceramics International, 2012
Chronic osteomyelitis is a challenging setback to the orthopedic surgeons in deciding an optimal therapeutic strategy. Conversely, patients feel frustrated of the therapeutic outcomes and development of adverse drug effects, if any. Present investigation deals with extensive approach incorporating in vivo animal experimentation and human application to treat chronic osteomyelitis, using antibiotic loaded porous hydroxyapatite scaffolds. Micro-to macro-porous hydroxyapatite scaffolds impregnated with antibiotic ceftriaxone-sulbactam sodium (CFS) were fabricated and subsequently evaluated by in vivo animal model after developing osteomyelitis in rabbit tibia. Finally 10 nos. of human osteomyelitis patients involving long bone and mandible were studied for histopathology, radiology, pus culture, 3D CT etc. up to 8-18 months post-operatively. It was established up to animal trial stage that 50N50H samples [with 50-55% porosity, average pore size 110 μm, higher interconnectivity (10-100 μm), and moderately high drug adsorption efficiency (50%)] showed efficient drug release up to 42 days than parenteral group based on infection eradication and new bone formation. In vivo human bone showed gradual evidence of new bone formation and fracture union with organized callus without recurrence of infection even after 8 months. This may be a new, alternative, cost effective and ideal therapeutic strategy for chronic osteomyelitis treatment in human patients.