RESUMO
The present work reports the adsorption, release, antibacterial properties, and in vitro cytotoxicity of sodium fusidate (SF) associated with a carbonated calcium phosphate bone cement. The adsorption study of SF on cement powder compared to stoichiometric hydroxyapatite and nanocrystalline carbonated apatite was investigated to understand the interaction between this antibiotic and the calcium phosphate phases involved in the cement formulation and setting reaction. The adsorption data revealed a fast kinetic process. However, the evolution of the amount of adsorbed SF was well described by a Freundlich-type isotherm characterized by a low adsorption capacity of the materials toward the SF molecule. The in vitro release results indicated a prolonged and controlled SF release for up to 34 days. The SF amounts eluted daily were at a therapeutic level (0.5-2 mg/L) and close to the antibiotic minimum inhibitory concentration (0.1-0.9 mg/L). Furthermore, the release data fitting and modeling suggested that the drug release occurred mainly by a diffusion mechanism. The antibacterial activity showed the effectiveness of SF released from the formulated cements against Staphylococcus aureus. Furthermore, the biological in vitro study demonstrated that the tested cements didn't show any cytotoxicity towards human peripheral blood mononuclear cells and did not significantly induce inflammation markers like IL-8.
Assuntos
Antibacterianos , Cimentos Ósseos , Fosfatos de Cálcio , Liberação Controlada de Fármacos , Ácido Fusídico , Staphylococcus aureus , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/administração & dosagem , Antibacterianos/toxicidade , Humanos , Staphylococcus aureus/efeitos dos fármacos , Fosfatos de Cálcio/química , Cimentos Ósseos/química , Cimentos Ósseos/farmacologia , Adsorção , Ácido Fusídico/farmacologia , Ácido Fusídico/química , Ácido Fusídico/administração & dosagem , Sobrevivência Celular/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Leucócitos Mononucleares/efeitos dos fármacos , CinéticaRESUMO
Two eco-friendly and highly efficient adsorbents, namely brushite-chitosan (DCPD-CS), and monetite-chitosan (DCPA-CS) composites were synthesized via a simple and low-cost method and used for tetracycline (TTC) removal. The removal behavior of TTC onto the composite particles was studied considering various parameters, including contact time, pollutant concentration, and pH. The maximum TTC adsorption capacity was 138.56 and 112.48 mg/g for the DCPD-CS and DCPA-CS, respectively. Increasing the pH to 11 significantly enhanced the adsorption capacity to 223.84 mg/g for DCPD-CS and 205.92 mg/g for DCPA-CS. The antibiotic adsorption process was well-fitted by the pseudo-second-order kinetic and Langmuir isotherm models. Electrostatic attractions, complexation, and hydrogen bonding are the main mechanisms governing the TTC removal process. Desorption tests demonstrated that the (NH4)2HPO4 solution was the most effective desorbing agent. The developed composites were more efficient than DCPD and DCPA reference samples and could be used as valuable adsorbents of TTC from contaminated wastewater.
Assuntos
Quitosana , Ácidos Ftálicos , Poluentes Químicos da Água , Quitosana/química , Adsorção , Fosfatos de Cálcio , Tetraciclina , Cinética , Antibacterianos , Poluentes Químicos da Água/análise , Concentração de Íons de HidrogênioRESUMO
This work aims to develop an injectable and antibacterial composite cement for bone substitution and prevention/treatment of bone infections. This cement is composed of calcium phosphate, calcium carbonate, bioactive glass, sodium alginate, and ciprofloxacin. The effect of ciprofloxacin on the microstructure, chemical composition, setting properties, cohesion, injectability, and compressive strength was investigated. The in vitro drug release kinetics and the antibacterial activity of ciprofloxacin-loaded composites against staphylococcus aureus and Escherichia coli pathogens were investigated. XRD and FTIR analysis demonstrated that the formulated cements are composed of a nanocrystalline carbonated apatite analogous to the mineral part of the bone. The evaluation of the composite cement's properties revealed that the incorporation of 3 and 9 wt% of ciprofloxacin affects the microstructural and physicochemical properties of the cement, resulting in a prolonged setting time, and a slight decrease in injectability and compressive strength. The in vitro drug release study revealed sustained release profiles over 18 days. The amounts of ciprofloxacin released per day (0.2 -15.2 mg/L) depend on the cement composition and the amount of ciprofloxacin incorporated. The antibacterial activity of ciprofloxacin-loaded cement composites attested to their effectiveness to inhibit the growth of Staphylococcus aureus and Escherichia coli.
Assuntos
Ciprofloxacina , Infecções Estafilocócicas , Humanos , Ciprofloxacina/farmacologia , Cinética , Antibacterianos/farmacologia , Antibacterianos/química , Apatitas/química , Apatitas/farmacologia , Fosfatos de Cálcio/farmacologia , Staphylococcus aureus , Escherichia coli , Cimentos Ósseos/farmacologia , Cimentos Ósseos/químicaRESUMO
A composite based on hydroxyapatite (HA) and chitosan (CS) combined with ciprofloxacin (CIP) was formulated by the solid-liquid mixing method. The optimization of the solid to the liquid ratio and the use of chitosan in a small amount (≤5 wt%) promoted the preparation of stable and rigid monoliths. A synergistic effect of CS and CIP contents on the compressive strength of the CIP-loaded composite was evidenced. The compressive strength of the fabricated biocomposite ranged in values from 1 to 6 MPa, comparable to those reported for cancellous bone. The improvement of the mechanical properties with the increase of the rate of organic components was correlated with the diminution of the surface area and the reduction in the pore volume of the specimens. On the other hand, the in vitro release experiments of the antibiotic indicated a sustained and controlled release of CIP over 10 days. Moreover, in vitro antibacterial tests performed on the biocomposite HA-CS5-CIP showed significant inhibition of Staphylococcus aureus and Escherichia coli pathogens. According to the showed results, the formulated composite with three-phase components could be a promising material for bone repair and local antibiotic release for the treatment of bone infections.
Assuntos
Antibacterianos/farmacologia , Força Compressiva , Durapatita/química , Quitosana/química , Ciprofloxacina/química , Preparações de Ação Retardada/farmacologia , Escherichia coli/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Espectroscopia de Infravermelho com Transformada de Fourier , Staphylococcus aureus/efeitos dos fármacos , Termogravimetria , Difração de Raios XRESUMO
The introduction of an antibiotic, sodium fusidate (SF), into the liquid phase of calcium carbonate-calcium phosphate (CaCO3-CaP) bone cement was evaluated, considering the effect of the liquid to powder ratio (L/P) on the composition and microstructure of the set cement and the injectability of the paste. In all cases, we obtained set cements composed mainly of biomimetic carbonated apatite analogous to bone mineral. With this study, we evi-denced a synergistic effect of the L/P ratio and SF presence on the injectability (i.e., the filter-pressing pheno-menon was suppressed) and the setting time of the SF-loaded cement paste compared to reference cement (without SF). In addition, the in vitro study of SF release, according to the European Pharmacopoeia recommendations, showed that, regardless of the L/P ratio, the cement allowed a sustained release of the antibiotic over 1month in sodium chloride isotonic solution at 37°C and pH7.4; this release is discussed considering the microstructure characteristics of SF-loaded cements (i.e., porosity, pore-size distribution) before and after the release test. Finally, modelling antibiotic release kinetics with several models indicated that the SF release was controlled by a diffusion mechanism.