A New Type of Biphasic Calcium Phosphate Cement as a Gentamicin Carrier for Osteomyelitis (original) (raw)
Related papers
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.
ACS Applied Materials & Interfaces, 2016
Osteomyelitis, an infectious disease predominantly tied to poor sanitary conditions in underdeveloped regions of the world, is in need of inexpensive, easily in situ synthesizable and administrable materials for its treatment. The results of this study stem from the attempt to create one such affordable and minimally invasive therapeutic platform in the form of a self-setting, injectable cement with a tunable drug release profile, composed of only nanoparticulate hydroxyapatite, the synthetic version of the bone mineral. Cements comprised two separately synthesized hydroxyapatite powders, one of which, HAP2, was precipitated abruptly, retaining the amorphous nature longer, and the other one of which, HAP1, was precipitated at a slower rate, more rapidly transitioning to the crystalline structure. Cements were made with four different weight ratios of the two hydroxyapatite components: 100/ 0, 85/15, 50/50, and 0/100 with respect to HAP1 and HAP2. Both the setting and the release rates measured on two different antibiotics, vancomycin and ciprofloxacin, were controlled using the weight ratio of the two hydroxyapatite components. Various inorganic powder properties were formerly used to control drug release, but here we demonstrate for the first time that the kinetics of the mechanism of formation of a solid compound can be controlled to produce tunable drug release profiles. Specifically, it was found that the longer the precursor calcium phosphate component of the cement retains the amorphous nature of the primary precipitate, the more active it was in terms of speeding up the diffusional release of the adsorbed drug. The setting rate was, in contrast, inversely proportional to the release rate and to the content of this active hydroxyapatite component, HAP2. The empirical release profiles were fitted to a set of equations that could be used to tune the release rate to the therapeutic occasion. All of the cements loaded with vancomycin or ciprofloxacin inhibited the growth of Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli and Pseudomonas aeruginosa in both agar diffusion assays and broth dilution tests with intensities *
Enhanced drug delivery of antibiotic-loaded acrylic bone cements using calcium phosphate spheres
Journal of applied biomaterials & functional materials, 2015
Local infection near an implant may pose a serious problem for patients. Antibiotic delivery from acrylic (poly(methyl methacrylate)-based) cements is commonly used to prevent and treat infections in the proximity of, e.g., hip joint implants. However, at present, the drug release properties of PMMA cements are not optimal. An initial burst followed by very slow release means that an unnecessarily large amount of antibiotic needs to be added to the cement, increasing the risk of bacterial resistance. The main purpose of this study was to enhance drug delivery from PMMA cements without influencing the mechanical properties. We incorporated strontium-doped calcium phosphate spheres (SCPS) into PMMA cement to enhance the antibiotic release and potentially improve the bone-cement integration. The release of strontium and vancomycin was investigated using inductively coupled plasma atomic emission spectroscopy and UV spectrophotometry, respectively. It was found that incorporating SCPS i...
Journal of Advanced Pharmaceutical Technology & Research, 2012
Many works have demonstrated the real potential of gentamicin-monoolein-water formulations as bioresorbable and sustained-release implants for the local treatment of the chronic osteomyelitis. In order to improve the efficacy of this type of implant, the incorporation of hydroxyapatite, a well-known osteointegrator material, is thought to be an interesting approach. Five formulations incorporating 0, 2.5, 5, 10, and 20% of hydroxyapatite were examined with regard to their physicochemical and in vitro drug release characteristics. The rheological, thermal (differential scanning calorimetric and thermogravimetric diffraction analysis), X-ray diffraction, and dissolution studies have showed that the presence of hydroxyapatite does not dramatically disturb the cubic liquid crystalline structure of the monoolein-water gel and their ability to progressively release the antibiotic. Implant 20% that was capable to release gentamicin sulfate over a period of four weeks without marked burst effect could be used as a more suitable biodegradable delivery system for the local management of chronic osteomyelitis.
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.
Hydroxyapatite - Antibiotic Applications in Bone Therapy
Journal of Research and Innovation for Sustainable Society, 2019
The aim of the current study is to prevent and reduce the number of bacterial infections in surgical implantation procedures. The hydroxyapatite is a calcium phosphate ceramic with important applications in the medicine and chemistry fields. The hydroxyapatite is a main mineral constituent of the hard tissues such as bones and teeth. The hydroxyapatite has remarkable properties including biocompatibility, bioactivity and ability to form a direct chemical bond with human hard tissues. Over the last decades, the biomedical orthopaedic and dentistry sectors have witnessed an unprecedented demand for a large variety and number of scaffolds, grafts, implants, and endo-prostheses. The increase in life expectancy, and the higher frequency of injuries and diseases are regarded as the main factors for this growing demand in orthopaedic and dental devices. The quality of life for millions of people has been drastically improved by using hydroxyapatite for bone repair and tissue regeneration. Recent findings in the realm of ion-substituted hydroxyapatite (HA) could pave the road towards significant developments in biomedicine, with an emphasis on a new generation of orthopaedic and dentistry applications, since such bioceramics are able to mimic the structural, compositional and mechanical properties of the bone mineral phase.
2019
This study was intended to formulate, characterize, evaluate in-vitro formulation release and dissolution studies of hydroxyapatite included microspheres of an antimicrobial drug for the disease osteomyelitis. Levofloxacin stacked hydroxyapatite microspheres were set up by inotropic gelation strategy by varing the measure of polymer and carrier. The microspheres of levofloxacin which was formulated were exposed to different physico-chemical parameters like size distribution, solubility studies, FT-IR, drug content, in-vitro dissolution studies, DSC and crystal morphology by SEM. FT-IR results has identified no traces of chemical interaction between the polymer and drug. SEM studies determined that the microspheres were framed in spherical and round shape. DSC curve demonstrated that the melting point of the polymer isn't influencing the melting point of the drug and affirmed that no chemical change among drug and polymer. Anti-microbial activity of formulated microspheres shown ...
Current Topics in the Utilization of Clay in Industrial and Medical Applications, 2018
Calcium phosphate cement (CPC) has limited use in bone repair due to their poor mechanical properties. Halloysite nanotubes (HNTs) are clay tubes with an aluminosilicate composition. The physicochemical properties, cytocompatibility, and cellular response to the CPC/HNT composites were assayed. Compression strength, FTIR analysis, protein synthesis, and mineralization were assessed. The cumulative data show that composites of tricalcium phosphate (TCP), anhydrous calcium diphosphate (DCPA) as the solid phase agent, and 10% chitosan lactate solution as the setting liquid produced cement with sustained release properties without loss of material strength. The composite also showed enhanced material properties (adhesiveness, surface roughness, and increased strength). Cellular assays confirm its osteoconductive and osteoinductive nature. CPCs, loaded with gentamicin-and neomycin-doped HNTs, showed sustained antibacterial release and marked zone of growth inhibition. CPCs fabricated with drugdoped HNTs offer a means for inducing bone growth at the site of implantation while controlling infection. This treatment modality should hasten patient healing time and enhance restoration of function. The increase in materials properties suggests that this CPC may be clinically applied to repair injuries in load-bearing bones.
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.