A biphasic nanohydroxyapatite/calcium sulphate carrier containing Rifampicin and Isoniazid for local delivery gives sustained and effective antibiotic release and prevents biofilm formation (original) (raw)
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Journal of Biomedical Materials Research Part A, 2007
Severe periodontitis treatment, where massive alveolar bone loss occurs, involves bone defect filling and intensive systemic log-term antibiotics administration. This study aims at developing novel injectable drug delivery systems (nanohydroxyapatite microspheres) with the drug releasing capability for periodontitis treatment and simultaneously initiating the osteointegration process. Materials were characterized by XRD, SEM, inverted stand optical microscope analysis, and mercury porosimetry method. Amoxicillin, amoxicillin þ clavulanic acid, and erythromycin were the antibiotics used. Release properties during 28 days from the hydroxyapatite (HA) granules, and two types of nanoHA microspheres were investigated. Biocompatibility was assessed by cytotoxicity assays. HA granules were inadequate, releasing all antibiotic during the first hours. The concentration of antibiotics released in the first days from HA-2 was higher than from HA-1 microspheres, because of the increased porosity and surface area. The release profiles (fast initial release followed by long-term sustained release) of effective doses of antibiotics make these systems good alternatives for antibiotics delivery. Osteoblasts proliferated well on both types of microspheres, being cell growth enhanced in the presence of antibiotics. Erythromycin presented the most beneficial effect. Combining the sustained antibiotic release with the osteoconduction, resorbability, and potential use as injectable bone filling material of porous HA microspheres, these systems provided a forth fold beneficial effect. 2007 Wiley Periodicals, Inc. J Biomed Mater Res 81A: [994][995][996][997][998][999][1000][1001][1002][1003][1004] 2007
Materials Science and Engineering: C, 2019
The use of high doses of antibacterial and anti-inflammatory drugs for patients with bone diseases, associated to implants or bone filling, can develop adverse effects; and consequently, it promotes to think new strategies to avoid this problem. In this work, it has been described the adsorption/release (or desorption) behavior of two drugs, ciprofloxacin (CIP) and ibuprofen (IBU), onto hydroxyapatite (nano-HA) at 37°C. Through Ultraviolet-Visible (UV-Vis) spectroscopy, the concentrations of both drugs in adsorption, kinetic and desorption processes were obtained. The Fourier Transformed-Infrared (FT-IR) spectroscopy, Zeta-potential (ζ-potential), High-Resolution Transmission Electron Microscopy (H-TEM) and x-Ray Diffraction (xRD) were also used to characterize bared nanoparticles and those with adsorbed drugs. Five adsorption models (Langmuir, Freundlich, Sips, Temkin and Dubinin-Radushkevich) were used for describing the behavior of both active compounds. The adsorption processes (CIP/nano-HA and IBU/nano-HA) were better predicted by the Sips model than by the others. The kinetic adsorption data were processed, for both active agents, by application of Avrami's model. Desorption/release process (of both drugs) was evaluated though Korsmeyer-Peppas (K-P) model. Owing to the predictability of these systems, we propose the use of these active ceramics as potential bone filler for improving the treatment against bacterial bone infections and to avoid its associated inflammatory process.
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...
The Kinetics of Ampicillin Release from Hydroxyapatite for Bones Regeneration
International Journal of Chemical Engineering, 2009
Semisynthetic beta-lactam antibiotics are among the most used pharmaceuticals. Their use in veterinary and human medicine is in continuous expansion. There is a growing need for developing bioactive implants. Advantages of implantable drug delivery tools can include high release efficiency, precise dose control, low toxicity, and allow to overcome disadvantages connected with conventional methods. In this respect, hydroxyapatite (HA) is an elective material. It enables to produce architectures similar to those of real bones. Here we studied a kinetic model to describe ampicillin release from HA. In the course of adsorption experiment, ampicillin was dissolved, maintained at 30 • C and shaken at 60 strokes/minute. Samples were withdrawn periodically for analysis and then returned to the mixture. Adsorbed amounts were measured by the difference of the concentration of the antibiotics before and after adsorption using UV adsorption at 225 nm. The aim of this work was to evaluate its application as ampicillin delivery carrier.
Biomaterials, 2001
As a potential therapy for periodontitis, sodium ampicillin, a broad spectrum antibiotic, was adsorbed onto hydroxyapatite (HA) and glass-reinforced hydroxyaptite (GR-HA) composites, and was subsequently released in vitro. The sodium ampicillin, was adsorbed more on HA compared to the GR-HA composites. X-ray di!raction (XRD) and Rietveld analysis were used to identify and quantify the levels of HA and-tricalcium phosphate (-TCP) in the microstructure of the GR-HA composites. Lattice parameters changes were observed for the-TCP phase dependant on the amount of glass added. The release kinetics were shown to be divided into three stages, the "rst of which where a large amount of sodium ampicillin is released, followed by a slower release rate and then a "nal stage where the release amount approaches zero, until no more sodium ampicillin was present. X-ray photoeletron spectroscopy (XPS) studies were carried out in order to ensure that the entire antibiotic adsorbed onto the materials had been released. These kinetics studies have indicated the possibility of using these materials as possible carriers for drug delivery. 2001 Elsevier Science Ltd. All rights reserved.
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.
Key Engineering Materials, 2004
Porous hydroxyapatite (HA) and glass reinforced hydroxyapatite (GRHA) with adequate macro and microporous structure were developed, aiming at being used as drug delivery carrier of antibiotics, for the in situ treatment of periodontitis. Materials were characterised by XRD and FTIR, presenting no changes from similar dense materials. Mercury intrusion porosimetry revealed micropores of less than 1 mm, accounting for 15% of the total porosity. Compression tests have shown close values for HA and GRHA, with the former showing slightly higher values of strength. Ampicillin adsorption was more effective on porous than on dense HA, and was similar for HA and GRHA.
Release of antibiotic from composites of hydroxyapatite and poly(lactic acid)
Journal of Controlled Release, 1985
We have recently revealed that a composite material prepared from hydroxyapatite and poly(lactic acid) can be used effectively as a substitute or a filler in the repair of bone defects. We have added the antibiotic Dideoxykanamycin B (DKB) to the composite to give it an antimicrobial property. To facilitate this purpose, D&-lactic acid oligomers were synthesized. The release of the drug has been studied experimentally both in vitro and in vivo. For the study of in vivo release we prepared cylindrical composites of 40% oligomer, 40% hydroxyapatite and 20% DKB, by weight. The composites were implanted into the fenestrated tibias of rats; after predetermined periods of time the animals were sacrificed. Post implantation it has been found that the release rate of DKB gradually decreases with time; however, DKB remains at the implant site in sufficient amounts to prevent bacterial growth for a few weeks. DKB was also found to be concentrated in the kidney; however, the amount was low. The composites from the lower molecular weight oligomer showed a higher release rate.
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 *
International journal of pharmaceutics, 2018
We report the development of effective drug loaded nanocarriers to combat multidrug resistant infection especially in case of osteomyelitis. The hollow mesoporous hydroxyapatite nanoparticles (hmHANPs) and solid/non-hollow hydroxyapatite nanoparticles (sHANPs) were synthesized by core-shell and co-precipitation techniques respectively. High encapsulation of the drug (ciprofloxacin) was observed in hmHANPs as compared to sHANPs, which may be due to the hollow porous structure of hmHANPs. These nanoparticles were characterized by scanning electron microscope (FESEM), N adsorption/desorption, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and Thermogravimetric analysis (TGA). Approximately 80% of the encapsulated drug was released at pH 4.5 within 5 days in case of hmHANPs while at pH 7.4, a sustained drug release profile was obtained and only 48.73% of the drug was released after 9 days. The results of kinetic drug release revealed that drug loaded hmHANPs sho...