Dual Mode Antibacterial Activity of Ion Substituted Calcium Phosphate Nanocarriers for Bone Infections (original) (raw)
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Scientific Reports
Long term multiple systemic antibiotics form the cornerstone in the treatment of bone and joint tuberculosis, often combined with local surgical eradication. Implanted carriers for local drug delivery have recently been introduced to overcome some of the limitations associated with conventional treatment strategies. In this study, we used a calcium sulphate hemihydrate (CSH)/nanohydroxyapatite (nHAP) based nanocement (NC) biomaterial as a void filler as well as a local delivery carrier of two standard of care tuberculosis drugs, Rifampicin (RFP) and Isoniazid (INH). We observed that the antibiotics showed different release patterns where INH showed a burst release of 67% and 100% release alone and in combination within one week, respectively whereas RFP showed sustained release of 42% and 49% release alone and in combination over a period of 12 weeks, respectively indicating different possible interactions of antibiotics with nHAP. The interactions were studied using computational m...
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 *
Biochimica et Biophysica Acta (BBA) - General Subjects, 2016
Background: Increasing resistance in bacteria towards antibiotics has made it imperative to research on their revitalization to combat infectious diseases. This study dealt with synthesis of a nano-form of the antibiotic tetracycline, its characterization and potency of killing different multi-drug resistant diarrhea-causing bacteria. Methods: Nano-formulation was done by loading tetracycline within biocompatible calcium phosphate nanoparticle. The synthesized tetracycline-loaded calcium phosphate nanoparticle (Tet-CPNP) was characterized by the techniques like TEM, DLS, EDS, FTIR, spectrofluorimetry and dialysis. Bctericidal activity of nano-particulate tetracycline was investigated by agar
ACS Omega
Multidrug resistance (MDR) is a global threat posed by continuously evolving microbial resistance against currently available antimicrobial agents. In this study, we synthesized hydroxyapatite-based porous nanocarriers with pH-dependent biodegradation, using cefazolin (CFZ) as cargo drug against MDR E. coli, S. aureus, and P. aeruginosa. Oval-shaped porous hydroxyapatite nanoparticles (opHANPs) were synthesized via core−shell method. Field emission scanning electron microscopy revealed that the average length and width of opHANPs were found to be ∼90 and ∼110 nm, respectively with monodispersed size and morphology. The encapsulation efficiency (EE) of CFZ was observed to be dependent on the initial concentration of the drug (EE, 41.37−92.40% with 300−2000 μg/mL of CFZ). Brunauer−Emmett− Teller specific surface area and pore width of opHANPs were 166.73 m 2 /g and 3.3 nm, respectively, indicating hierarchal pore distribution. The pH-responsive drug release was observed from CFZ-loaded opHANPs (CFZ@opHANPs). An enhanced drug-releasing behavior was observed at lower pH (4.5, 2.5, and 1.5). The study of release kinetics revealed that at pH 7.4, drug release is due to anomalous diffusion, while at lower pH, the drug release followed fickian diffusion model. Cytotoxic and hemolytic studies showed biocompatibility of CFZ@opHANPs with HepG2 and red blood cells. The growth kinetic study and colony-forming unit assay showed the superior antibacterial potential of CFZ@opHANPs, in contrast to carrier or CFZ alone, against MDR E. coli, S. aureus, and P. aeruginosa strains.
Revista de Chimie
The hydroxyapatite (HA) nano and microparticles were synthesized by wet-chemical precipitation in order to use them as drug carriers for biomedical applications. Scanning Electron Microscopy (SEM), Dynamic Light Scattering (DLS) and Fourier Transform Infrared Spectroscopy (FTIR) were performed to assess their size, external morphology and chemical composition. The properties of HA particles as drug carriers for antibiotics delivery were evaluated with doxycycline and chloramphenicol. The amount of drug loading and release was determined by UV-Visible spectrophotometry. The antibacterial properties of loaded HA particles were evaluated using gram-positive Bacillus subtilis bacteria and gram-negative Pseudomonas aeruginosa bacteria. The synthesized particles of HA exhibit a high adsorption capacity (around 99%) and good controlled release properties for doxycycline. The adsorption of chloramphenicol on HA was extremely low (about 2%). According to the results, the compatibility betwee...
Background: Increasing resistance in bacteria towards antibiotics has made it imperative to research on their revitalization to combat infectious diseases. This study dealt with synthesis of a nano-form of the antibiotic tetracycline, its characterization and potency of killing different multi-drug resistant diarrhea-causing bacteria. Methods: Nano-formulation was done by loading tetracycline within biocompatible calcium phosphate nanoparticle. The synthesized tetracycline-loaded calcium phosphate nanoparticle (Tet-CPNP) was characterized by the techniques like TEM, DLS, EDS, FTIR, spectrofluorimetry and dialysis. Bactericidal activity of nano-particulate tetracycline was investigated by agar plating, spectrophotometry, phase contrast-fluorescence-atomic force microscopy and flow cytometry techniques. Results: The Tet-CPNPs were 8 ± 5 nm in size and nearly spherical in shape, efficiency of tetracycline loading in CPNP was about 20% and the release of antibiotic from Tet-CPNPs was sustainable during 7 days. Minimum inhibitory concentration (MIC) of Tet-CPNP on multiple antibiotic (including tetracycline) resistant bacteria like Escherichia coli, Salmonella kentuckey and Shigella flexneri was in the range of 20-40 μg/ml, whereas MIC of free tetracycline was in the range of 150-180 μg/ml. NP-mediated cell filamentation and cell membrane disintegration caused cell killing. Moreover, death of Shigella-infected Zebra fish larvae was stalled by Tet-CPNP treatment. CPNP itself had no toxic effect on bacteria as well as on Zebra fish. Conclusion: Our nano-formulation of tetracycline might reclaim a nearly obsolete antibiotic to further potential function.
Prolonged local antibiotics delivery from hydroxyapatite functionalised with cyclodextrin polymers
Biomaterials, 2009
Per-operative infection is a common complication for bone-graft surgery. Combining antiseptic agents with graft materials may offer a solution by increasing local drug concentration at target sites. Aiming to achieve a sustained local antibiotic (ATB) delivery for a widely applied bone substitute materialhydroxyapatite (HA), we attempted incorporating hydroxypropyl-b-cyclodextrin polymer (polyHPbCD) into microporous HA via impregnating either in a CD monomers mixture solution or a pre-synthesized CD polymer solution, followed by thermal fixation processing. In such functionalised material (CD-HA), polyHPbCD could entrap ATBs and release them progressively. Infrared-spectroscopic analysis confirmed the presence of polyHPbCD in functionalised HA via both processing pathways; polyHPbCD functionalisation yields were quantitated by thermogravimetric analysis for optimising the processing regime. Ciprofloxacin (CFX) and vancomycin (VCM), commonly applied in orthopaedics, have been respectively loaded on CD-HA by dip-coating. For both ATBs, kinetic release test in phosphate buffered saline showed significantly increased initial-burst amount and prolonged release from CD-HA compared with those from non-functionalised HA. Encouragingly, ATBs loaded CD-HA also revealed a prolonged bacteriostatic activity against Staphylococcus aureus and progressively increased cytocompatibility to osteoblasts (MC3T3-E1). Overall, polyHPbCD functionalisation on HA could be an effective drug-delivery model for loading different drug molecules in prevention of infection.
2003
Alternative drug delivery for the treatment of resistant bacterial infections is necessary to bypass existing antibiotic resistance mechanism and ensure direct delivery of the drug to the targeted site using locally sourced materials to minimize cost in the long term. In this study, cockle shell-derived calcium carbonate aragonite nanoparticles (CS-CaCO 3 NP) was synthesized, loaded with oxytetracycline (OTC), and characterized using Zeta analysis, Transmission electron microscopy (TEM), FESEM, X-ray Diffraction (XRD), Fourier Transform Infrared (FTIR) and Brunauer-Emmett-Teller analysis. The loaded OTC-CS-CaCO 3 NP was further characterized after which the in vitro release of OTC was studied. A homogenously spherical CS-CaCO 3 NP was observed on TEM with a mean diameter of 29.90 nm and −19.9 zeta potential which increased to 62.40 nm and −23.5, respectively, after OTC loading. XRD and FTIR analysis of OTC-CS-CaCO 3 NP revealed that OTC maintained its functionality and crystallinity. The formulation of OTC:CS-CaCO 3 NP in ratio 1:4 with drug encapsulating efficiency (71%) was used for in vitro release studies. OTC was sustainably released from OTC-CS-CaCO 3 NP over a period of 96 hours. Our results suggest that OTC-CS-CaCO 3 NP is a promising nanoparticle antibiotic delivery system with efficient physicochemical and pharmacological properties whose antibiotic properties should be further investigated.
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...