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The study aimed to assess the health value and safety associated with the consumption of the chosen 37 beetroot-based dietary supplements (DSs). An optimized and validated analytical procedure, using a method called microwave plasma atomic emission spectrometry (MP-AES), was developed to determine the profiles of 19 elements (Na, K, Fe, Ca, Pt, Zn, Cd, Cu, V, Co, Ni, Pb, Mo, Mg, Al, Mn, Sr, Cr, Ba) in the DSs. The products were assessed for compliance with the recommended daily doses for the chosen elements, and any deviations were identified. Results showed that powders constituted a richer source of elements than capsules and tablets. The exception was iron-enriched products, which provided the highest dose of Fe (3.75 to 25 mg/daily dose). Safety assessment was evaluated in 3 steps, including (1) the determination of levels of Al, Ba, Cd, and Pb; (2) comparison of their content with the permissible contamination limits; and (3) comparison of the weekly or monthly intake of Al and Cd with the provisional tolerable weekly (PTWI) or monthly (PTMI) intake, respectively. The content of Ba was evaluated because of the oral reference dose (RfD). Five products were significantly contaminated with Cd (4-134% of PTMI Cd), two with Al (11-12%), and three with Ba (1.085-1.331 µg/d.d.). Lead was not detected above the LOQ (0.035 mg/kg). Factor analysis was employed to differentiate between the pharmaceutical forms (capsules, tablets, and powders) and determine the origin of the powder contained in the capsules. These results highlight the importance of implementing more stringent control measures and regulatory changes in the DSs market to ensure consumer safety.
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Local delivery of antibiotics has gained increasing interest in the treatment of osteomyelitis due to its effectiveness and safety. Since the regeneration of bone tissue at the site of infection is as important as bacterial eradication, implantable drug delivery systems should not only release the drugs in a proper manner but also exert the osseointegration capability. Herein, we present an implantable drug delivery system in a scaffold form with a unique set of features for local treatment of osteomyelitis. For the first time, collagen type I, ciprofloxacin-loaded mesoporous silica, and bioglass were combined to obtain scaffolds using the molding method. Drug-loaded mesoporous silica was blended with polydimethylsiloxane to prolong the drug release, whereas bioglass served as a remineralization agent. Collagen-silica scaffolds were evaluated in terms of physicochemical properties, drug release rate, mineralization potential, osteoblast response in vitro, antimicrobial activity, and biological properties using an in vivo preclinical model - chick embryo chorioallantoic membrane (CAM). The desirable multifunctionality of the proposed collagen-silica scaffolds was confirmed. They released the ciprofloxacin for 80 days, prevented biofilm development, and induced hydroxyapatite formation. Moreover, the resulting macroporous structure of the scaffolds promoted osteoblast attachment, infiltration, and proliferation. Collagen-silica scaffolds were also biocompatible and effectively integrated with CAM.
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Antibacterianos , Osteomielitis , Embrión de Pollo , Animales , Antibacterianos/farmacología , Andamios del Tejido/química , Dióxido de Silicio/química , Sistemas de Liberación de Medicamentos , Colágeno/química , Huesos , Ciprofloxacina/farmacología , Osteomielitis/tratamiento farmacológico , Porosidad , Materiales Biocompatibles/química , Regeneración ÓseaRESUMEN
Due to the high content of bioactive substances, beetroot and its preserves might be a valuable constituent of a diet. Research into the antioxidant capacity and content of nitrate (III) and (V) in beetroot-based dietary supplements (DSs) worldwide is limited. The Folin-Ciocalteu method, CUPRAC, DPPH, and Griess methods were used to determine total antioxidant capacity, total phenolic content, nitrites, and nitrates content in fifty DSs and twenty beetroot samples. Moreover, the safety of products was evaluated because of the concentration of nitrites, nitrates, and the correctness of labelling. The research showed that a serving of fresh beetroot provides significantly more antioxidants, nitrites, and nitrates than most daily portions of DSs. Product P9 provided the highest dose of nitrates (169 mg/daily dose). However, in most cases, the consumption of DSs would be associated with a low health value. The acceptable daily intake was not exceeded in the cases of nitrites (0.0015-0.55%) and nitrates (0.056-48%), assuming that the supplementation followed the manufacturer's recommendation. According to European and Polish regulations, 64% of the products tested did not meet all the requirements for labelling food packaging. The findings point to the need for tighter regulation of DSs, as their consumption might be dangerous.
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Osseointegration is a fundamental process during which implantable biomaterial integrates with host bone tissue. The surgical procedure of biomaterial implantation is highly associated with the risk of bacterial infection. Thus, the research continues for biodegradable bone void fillers which are able to stimulate the bone tissue regeneration and locally deliver the antibacterial agent. Herein, we obtained bifunctional bioglass (BG) using novel, preoptimized, rapid one-pot synthesis. Following the ISO Standards, the influence of the obtained BG on osteoblast-mediated phenomena, such as osteoconduction and osteoinduction was assessed and compared to two commercial materials: bioactive glass powder 45S and bioactive glass powder 85S. Direct-contact tests revealed osteoblast adhesion to BG particles; whereas, tests on extracts confirmed high viability of cells incubated with BG extract. Analyses of gene expression, alkaline phosphatase activity, and calcium phosphates deposition confirmed the stimulation of early and late stages of osteoblast differentiation and mineralization. Additionally, an extended evaluation of intracellular calcium fluctuations revealed a possible correlation between osteoblast calcium uptake and extracellular matrix mineralization. Moreover, proposed bioglass exhibited satisfactory doxycycline adsorption capacity and release profile. The obtained results confirmed the bifunctionality of the proposed BG and indicated its potential as osseointegrative bone drug delivery system.
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Materiales Biocompatibles , Calcio , Calcio/metabolismo , Polvos/metabolismo , Materiales Biocompatibles/metabolismo , Cerámica , Osteoblastos , Sistemas de Liberación de Medicamentos , VidrioRESUMEN
Our aim was to assess the mineral composition as well as the physicochemical quality of green tea-based dietary supplements (capsules and tablets) with respect to average weight, size and shape, friability, breaking force and disintegration time. Products were analysed by flame atomic absorption spectrometry for Ca, K, Mg, Na, Cr, Cu, Fe, Zn, Mn, Pb and Cd. Approximately 60% of the analysed supplements met the requirements of European and Polish regulations. The dietary supplements passed weight variation tests, but not all products had compliant capsule sizes. One product in tablet form failed the friability test, and eleven dietary supplements in tablet form failed the disintegration test. The supplements were characterised by a varied elemental composition, with the highest values found for Ca, Fe, Zn and Mn. The recommended daily allowance realisation for Fe and Zn in two dietary supplements (capsule form) exceeded 100%. As a result of the estimation of the monthly intake of toxic metals, it was concluded that the tested products do not pose a risk to consumer health. Significant relationships (p < 0.001) were found for K, Mg, Na, Cu, Fe, Mn and Zn. The application of factor and cluster analyses allowed the verification of the similarity of green tea extracts contained in dietary supplements to the natural raw material, green tea leaves, used as a reference material.
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The dangerous effects of oxidative stress can be alleviated by antioxidantssubstances with the ability to prevent damage caused by reactive oxygen species. The adsorption of antioxidants onto nanocarriers is a well-known method that might protect them against rough environ-mental conditions. The aim of this study was to investigate the adsorption and desorption of gallic acid (GA), protocatechuic acid (PCA), chlorogenic acid (CGA), and 4-hydroxybenzoic acid (4-HBA) using commercially available mesoporous silica materials (MSMs), both parent (i.e., SBA-15 and MCM-41) and surface functionalized (i.e., SBA-NH2 and SBA-SH). The MSMs loaded with active compounds were characterized using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy with energy-dispersive X-ray spectroscopy (SEM-EDX), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), thermoporometry (TPM), and powder X-ray diffraction (XRD). High-performance liquid chromatography (HPLC-CAD) was used to evaluate the performance of the adsorption and desorption processes. The antioxidant potential was investigated using the Folin−Ciocalteu (FC) spectrophotometric method. Among the studied MSMs, the highest adsorption of GA was observed for amine-modified SBA-15 mesoporous silica. The adsorption capacity of SBA-NH2 increased in the order of PCA, 4-HBA < GA < CGA. Different desorption effectiveness levels of the adsorbed compounds were observed with the antioxidant capacity preserved for all investigated compounds.
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In the European Union, no specific requirements for the physicochemical parameters of dietary supplements have been established, contrary to the United States of America. This research aimed to assess the selected physical parameters of 31 commercially available beetroot-based dietary supplements in the form of tablets and capsules following the United States Pharmacopoeia (USP) guidelines and the Food and Drug Administration (FDA) recommendations. There was also estimated zinc and iron content by atomic absorption spectroscopy with flame detection. Results showed that nine products did not meet the USP requirements. Seven supplements needed more than 30 min to disintegrate. Two products in the form of tablets did not pass the friability test because of cracking. The hardness values varied significantly between manufacturers, demonstrating values from 59.1 to 455.8 N. The iron-enriched supplements differed significantly in iron content compared with the manufacturers' declaration (84.91-140.69%). Inappropriate quality of dietary supplements, which may constitute a potential risk to consumers, can be related to the lack of specific regulations in Europe; hence, similar to the USA requirements should be considered in the European Union. The work emphasizes the need to better control the quality of dietary supplements before they are introduced to the European market.
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For decades, local bone drug delivery systems have been investigated in terms of their application in regenerative medicine. Among them, inorganic polymers based on amorphous silica have been widely explored. In this work, we combined two types of amorphous silica: bioglass and doxycycline-loaded mesoporous silica MCM-41 into the form of spherical granules (pellets) as a bifunctional bone drug delivery system. Both types of silica were obtained in a sol-gel method. The drug adsorption onto the MCM-41 was performed via adsorption from concentrated doxycycline hydrochloride solution. Pellets were obtained on a laboratory scale using the wet granulation-extrusion-spheronization method and investigated in terms of physical properties, drug release, antimicrobial activity against Staphylococcus aureus, mineralization properties in simulated body fluid, and cytotoxicity towards human osteoblasts. The obtained pellets were characterized by satisfactory mechanical properties which eliminated the risk of pellets cracking during further investigations. The biphasic drug release from pellets was observed: burst stage (44% of adsorbed drug released within the first day) followed by prolonged release with zero-order kinetics (estimated time of complete drug release was 19 days) with maintained antimicrobial activity. The progressive biomimetic apatite formation on the surface of the pellets was observed. No cytotoxic effect of pellets towards human osteoblasts was noticed.
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Sustitutos de Huesos/administración & dosificación , Sustitutos de Huesos/química , Cerámica/química , Sistemas de Liberación de Medicamentos , Dióxido de Silicio/administración & dosificación , Dióxido de Silicio/química , Adsorción , Antibacterianos/administración & dosificación , Antibacterianos/farmacocinética , Regeneración Ósea , Sustitutos de Huesos/farmacocinética , Calcificación Fisiológica , Rastreo Diferencial de Calorimetría , Doxiciclina/administración & dosificación , Doxiciclina/farmacocinética , Portadores de Fármacos/administración & dosificación , Portadores de Fármacos/química , Humanos , Técnicas In Vitro , Ensayo de Materiales , Microscopía Electrónica de Rastreo , Tamaño de la Partícula , Medicina Regenerativa , Espectrometría por Rayos X , Espectroscopía Infrarroja por Transformada de Fourier , Staphylococcus aureus/efectos de los fármacosRESUMEN
There is a lack of data on the actual composition and effectiveness of beetroot-based dietary supplements. The research aimed to determine the profile of 22 elements (Na, K, Ca, Mg, P, Fe, As, Se, Zn, Cu, Ag, Co, Ni, Mo, Al, Mn, Sr, Cr, Ba, Li, Pb, Cd) in beetroot and its supplements by the microwave plasma atomic emission spectrometry (MP-AES) method. The analytical procedure was optimised and validated. The composition of both groups was compared, assessing compliance with the recommended daily doses for the chosen elements, and the health risk was estimated. Furthermore, chemometric analysis was applied. Beetroots constituted a significant source of elements, especially K, Na, Mg, Ca, P, in contrast to supplements which contained their negligible amounts except from iron-enriched products which provided notable amounts of Fe (38.3-88% of the Recommended Dietary Allowance for an adult male from 19 to 75 years old). Some products were significantly contaminated with toxic elements (As, Cd). Factor and cluster analyses were helpful in the differentiation of beetroot and its supplements in view of their type (vegetable, supplement, iron-enriched supplement), origin, type of cultivation (conventional, organic), and form (capsule, tablet) based on their mineral composition. The obtained results indicate the need for more stringent control of supplements, as they may pose a significant health risk to consumers.
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Beta vulgaris/química , Quimiometría/métodos , Suplementos Dietéticos/análisis , Minerales/química , Raíces de Plantas/química , Suplementos Dietéticos/toxicidad , Humanos , Factores de RiesgoRESUMEN
Herein, the microwave-assisted wet precipitation method was used to obtain materials consisting of mesoporous silica (SBA-15) and calcium orthophosphates (CaP). Composites were prepared through immersion of mesoporous silica in different calcification coating solutions and then exposed to microwave radiation. The composites were characterized in terms of molecular structure, crystallinity, morphology, chemical composition, and mineralization potential by Fourier-transform infrared spectroscopy (FTIR), powder X-ray diffraction (XRD), and scanning electron microscopy equipped with energy-dispersive X-ray spectroscopy (SEM-EDX). The application of microwave irradiation resulted in the formation of different types of calcium orthophosphates such as calcium deficient hydroxyapatite (CDHA), octacalcium phosphate (OCP), and amorphous calcium phosphate (ACP) on the SBA-15 surface, depending on the type of coating solution. The composites for which the progressive formation of hydroxyapatite during incubation in simulated body fluid was observed were further used in the production of final pharmaceutical forms: membranes, granules, and pellets. All of the obtained pharmaceutical forms preserved mineralization properties.
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For decades, bone drug delivery systems dedicated for osteomyelitis treatment have been investigated as bifunctional materials that exhibit prolonged drug release and mineralization potential. Herein, composite-type pellets based on cefazolin-loaded amino-modified mesoporous silica SBA-15 and microwave-assisted hydroxyapatite were investigated as potential bone drug delivery system in vitro. Pellets were obtained by granulation, extrusion and spheronization methods in laboratory scale and studied in terms of physical properties, drug release, mineralization potential, antimicrobial activity and cytotoxicity towards human osteoblasts. The obtained pellets were characterized for hardness and friability which indicated the pellets durability during further investigations. Prolonged (5-day) release of cefazolin from pellets was observed. The pellets exhibited mineralization potential in simulated body fluid, i.e., a continuous layer of bone-like apatite was formed on the surface of pellets after 28 days of incubation. An antimicrobial assay of pellets revealed an antibacterial effect against Staphylococcus aureus strain during 6 days. No cytotoxic effects of pellets towards human osteoblasts were observed. The obtained results proved that proposed pellets appear to have potential applications as bone drug delivery systems.
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Antibacterianos/química , Cefazolina/química , Portadores de Fármacos , Dióxido de Silicio/química , Antibacterianos/administración & dosificación , Antibacterianos/toxicidad , Cefazolina/administración & dosificación , Cefazolina/toxicidad , Línea Celular , Preparaciones de Acción Retardada , Composición de Medicamentos , Implantes de Medicamentos , Liberación de Fármacos , Durapatita/química , Dureza , Humanos , Cinética , Osteoblastos/efectos de los fármacos , Osteomielitis/tratamiento farmacológico , Osteomielitis/microbiología , Porosidad , Dióxido de Silicio/toxicidad , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/crecimiento & desarrollo , Propiedades de SuperficieRESUMEN
We reported the new biphasic composites of calcium phosphate and mesoporous silica material (CaP@MSi) in the form of powders and pellets as a potential bone drug delivery system for doxycycline hydrochloride (DOX). The CaP@MSi powders were synthesized by cationic surfactant-templating method. The effects of 10, 20, and 30% CaP content in the CaP@MSi powders on the molecular surface structure, the cytotoxicity against osteoblast cells in vitro, and the mineralization potential in simulated body fluid were investigated. The CaP@MSi characterized by the highest mineralization potential (30% CaP content) were used for DOX adsorption and pelletization process. The CaP which precipitated in the CaP@MSi composites was characterized as calcium-deficient with the Ca:P molar ratio between 1.0 and 1.2. The cytotoxicity assays demonstrated that the CaP content in MSi increases osteoblasts viability indicating the CaP@MSi (30% CaP content) as the most biocompatible. The combination of CaP and MSi was an effective strategy to improve the mineralization potential of parent material. Upon immersion in simulated body fluid, the CaP of composite converted into the bone-like apatite. The obtained pellets preserved the mineralization potential of CaP@MSi and provided the prolonged 5-day DOX release. The obtained biphasic CaP@MSi composites seem to have an application potential as bone-specific drug delivery system.
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Fosfatos de Calcio/química , Doxiciclina/farmacología , Osteoblastos/citología , Dióxido de Silicio/química , Adsorción , Línea Celular , Supervivencia Celular , Doxiciclina/química , Sistemas de Liberación de Medicamentos , Implantes de Medicamentos , Humanos , Osteoblastos/efectos de los fármacos , Porosidad , PolvosRESUMEN
In this study, we obtained novel solid films composed of ciprofloxacin-loaded mesoporous silica materials (CIP-loaded MCM-41) and polymer coating blends. Polymer coating blends were composed of ethylcellulose (EC) with various levels of polydimethylsiloxane (PDMS, 0, 1, 2% (v/v)). The solid films were prepared via the solvent-evaporation molding method and characterized by using scanning electron microscopy (SEM), optical profilometry, and wettability analyses. The solid-state of CIP present in the solid films was studied using X-ray diffraction (XRD) and differential scanning calorimetry (DSC). The release profiles of CIP were examined as a function of PDMS content in solid films. The surface morphology analysis of solid films indicated the progressive increase in surface heterogeneity and roughness with increasing PDMS content. The contact angle study confirmed the hydrophobicity of all solid films and significant impact of both PDMS and CIP-loaded MCM-41 on surface wettability. DSC and XRD analysis confirmed the presence of amorphous/semi-crystalline CIP in solid films. The Fickian diffusion-controlled drug release was observed for the CIP-loaded MCM-41 coated with PDMS-free polymer blend, whereas zero-order drug release was noticed for the CIP-loaded MCM-41 coated with polymer blends enriched with PDMS. Both the release rate and initial burst of CIP decreased with increasing PDMS content.
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Mesostructured ordered silica-based materials are the promising candidates for local drug delivery systems in bone disease due to their uniform pore size and distribution, and high surface area which affect their excellent adsorption properties, good biocompatibility and bioactivity, and versatile functionalization so that their properties can be controlled. Ordered mesoporous silica (MCM-41 type) was synthesized by a surfactant-assisted sol-gel process using tetraethoxysilane as a silica precursor and hexadecyltrimethylammonium bromide as the structure-directing agent. Functionalized silica materials containing various types of organic groups (3-aminopropyl, 3-mercaptopropyl, or 3-glycidyloxypropyl groups) were synthesized by the post-grafting method onto pre-made mesoporous silica. Comparative studies of their structural characteristics, the surface mineralization activity and release properties for the model drug Metronidazole (MT) were then conducted. It has been found that porosity parameters, mineralization activity and adsorption/release of metronidazole from mesoporous channels of silica can be regulated using functional groups which are chemically bounded with an outer silica surface. The preferential mineral nucleation was found on negatively charged surfaces-MCM-41, and mercaptopropyl and glycidyloxypropyl functionalized silica (MCM-SH and MCM-epoxy, respectively) in simulated body fluid (SBF solution), as well as a sustained release of MT. In contrast to them, aminopropyl-functionalized samples (MCM-NH2) achieved a high MT release rate. These results confirm the potential of silica-based materials for local therapeutic applications (as drug carriers and bone substitutes) in bone disease.
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Portadores de Fármacos/síntesis química , Metronidazol/administración & dosificación , Dióxido de Silicio/síntesis química , Adsorción , Enfermedades Óseas/tratamiento farmacológico , Portadores de Fármacos/química , Humanos , Porosidad , Dióxido de Silicio/química , Propiedades de SuperficieRESUMEN
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 differential scanning calorimetry (DSC), and in vitro antibiotic release. The antibacterial activity against Staphylococcus aureus (ATCC 6538) as well as the in vitro cytocompatibility to human osteoblasts of obtained composites were also examined. Physicochemical results confirmed the presence of particular components (FTIR), formation of continuous polymer phase onto the surface of freeze-dried CIP or MCM-41-CIP (SEM/EDX), and semi-crystalline (composites containing freeze-dried CIP) or amorphous (composites containing MCM-41-CIP) structure (XRD). TGA and DSC analysis indicated the high thermal stability of CIP adsorbed onto the MCM-41, and higher after MCM-41-CIP coating with polymer blend. The release study revealed the significant reduction in initial burst of CIP for the composites which contained MCM-41-CIP instead of freeze-dried CIP. These composites were also characterized by the 30-day activity against S. aureus and the highest cytocompatibility to human osteoblasts in vitro.
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Here, we report an inorganic hexagonally ordered mesoporous fibre-like carrier made of silica as an effective drug delivery system with mineralisation potential. Fibre-like SBA-15 has been modified by employing a simple surface activation (rehydroxylation) procedure. The surface-rehydroxylated fibre-like SBA-15 (SBA-15-R) was used to investigate the possible mechanism of hydroxyapatite (HA) nucleation and deposition onto silica's surface after immersion in simulated body fluid (SBF). Amorphous calcium phosphate, Ca-deficient HA and bone-like HA deposits were observed on SBA-15-R surface consecutively after 7, 14 and 21 days of immersion in SBF. Accordingly, our low-angle XRD, STEM and N2 adsorption/desorption results indicated that deposited ions were mostly located at the silica's surface and could modify the size of the mesopores. The SBA-15-R was studied in vitro as the potential bioactive drug delivery system using doxorubicin (DOX) as a model water-soluble and anticancer drug. The adsorbed DOX molecules were mostly located at the pore walls and pore openings, likely together with the silanol groups. The DOX release was diffusion-controlled and relatively slower in SBF (pH = 7.4) than in phosphate-buffered solution (pH = 5.0), most probably due to both the stronger electrostatic interactions occurring between the DOX and the SBA-15-R and the simultaneous deposition of calcium and phosphates ions from SBF.
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Enfermedades Óseas/tratamiento farmacológico , Portadores de Fármacos , Dióxido de Silicio/uso terapéutico , Antibacterianos/administración & dosificación , Antibacterianos/química , Líquidos Corporales/química , Doxorrubicina/administración & dosificación , Doxorrubicina/química , Sistemas de Liberación de Medicamentos , Durapatita , Humanos , Microscopía Electrónica de Rastreo , Estructura Molecular , Porosidad , Dióxido de Silicio/química , Solubilidad , Propiedades de Superficie , Difracción de Rayos XRESUMEN
The purpose of this study was to evaluate the surface mineralization activity and in vitro drug behavior potential of two forms of mesoporous silica: powder and granulate. Ordered mesoporous SiO2 powder was synthesized by surfactant-assisted sol-gel process using tetraethoxysilane as a silica precursor and hexadecyltrimethylammonium bromide as the structure-directing agent. The granulate was prepared using silica powder and ethyl cellulose as a binding agent. Metronidazole (MT)-an anti-inflammatory substance and doxorubicin hydrochloride (ChD)-an anti-cancer drug were chosen as drug models for delivery studies. The results of structural characteristic studies, utilizing transmission electron microscope (TEM) and scanning electron microscope (SEM) images, powder X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and nitrogen adsorption-desorption (BET) measurements, show that obtained materials have two-dimensional hexagonal p6mm symmetry, high specific surface area, narrow pore size, and a satisfactory mineralization behavior in the simulated body solution (SBF, pH = 7.4). The release rate of drugs depends upon the structural features of the drug molecules and the form of the carrier material. Of both the drugs analyzed, faster release was observed for small MT molecules characterized by weaker interactions with the carrier. In addition, the slower drug release was observed with granulate form due to increased diffusion barrier for drugs. Obtained results prove that the MT/ChD-loaded silica formulations could be attractive materials for filling bone defects and for local delivery systems.
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Enfermedades Óseas , Doxorrubicina/química , Metronidazol/química , Regeneración , Dióxido de Silicio/química , Antiinflamatorios/metabolismo , Antiinflamatorios/uso terapéutico , Antineoplásicos/química , Antineoplásicos/metabolismo , Antineoplásicos/uso terapéutico , Enfermedades Óseas/tratamiento farmacológico , Enfermedades Óseas/metabolismo , Preparaciones de Acción Retardada , Doxorrubicina/metabolismo , Doxorrubicina/uso terapéutico , Liberación de Fármacos , Metronidazol/metabolismo , Metronidazol/uso terapéutico , Porosidad , Polvos , Dióxido de Silicio/metabolismo , Dióxido de Silicio/uso terapéutico , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Difracción de Rayos XRESUMEN
The aim of this study was to evaluate the surface mineralization activity and in vitro drug behaviour potential of new mesoporous silica microparticles (MSM). The unmodified MSM (MSM-0%Ca) and calcium-modified MSM (MSM-5%Ca, MSM-15%Ca, MSM-25%Ca) were prepared using the self-assembling method. Calcium diethoxide was used as a calcium precursor. Doxorubicin hydrochloride (DOX), used as an anticancer model drug, was selected to the drug loading and release studies. The DOX loading into the microparticles was performed by liquid adsorption process. The self-formation of carbonate hydroxyapatite (C-Hap) on the MSM surface was examined under in vitro biomimetic conditions. The samples were characterised by means of scanning-transmission electron microscopy (STEM) and energy dispersive X-ray spectrometry, powder X-ray diffraction, Fourier transform infrared spectroscopy, and nitrogen adsorption-desorption measurements. The results indicated an inverse relationship--while increasing the total amount of calcium in the MSM composition the surface area and pore volume decrease with a simultaneous increase in the pore size. This was correlated with a progressive increase in the surface mineralization ability--especially its initial promotion, and in the decrease in MSM drug loading efficiency. The release rate of the DOX can be effectively tailored by varying the amount of calcium, where the elution rate of DOX increases with an increasing amount of the Ca precursor.
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Durapatita/química , Dióxido de Silicio/química , Sistemas de Liberación de Medicamentos/métodos , PorosidadRESUMEN
Collagen, the most abundant protein in mammals, is able to form fibrils, which have central role in tissue repair, fibrosis, and tumor invasion. As a component of skin, tendons, and cartilages, this protein contacts with any implanted materials. An inherent problem associated with implanted prostheses is their propensity to be coated with host proteins shortly after implantation. Also, silicone implants undergoing relatively long periods of contact with blood can lead to formation of thrombi and emboli. In this paper, we demonstrate the existence of interactions between siloxanes and collagen. Low-molecular-weight cyclic siloxane (hexamethylcyclotrisiloxane-D3) and polydimethylsiloxanes (PDMS) forming linear chains, ranging in viscosity from 20 to 12,000 cSt, were analyzed. We show that D3 as well as short-chain PDMS interact with collagen, resulting in a decrease in fibrillogenesis. However, loss of collagen native structure does not occur because of these interactions. Rather, collagen seems to be sequestered in its native form in an interlayer formed by collagen-siloxane complexes. On the other hand, silicone molecules with longer chains (i.e., PDMS with viscosity of 1000 and 12,000 cSt, the highest viscosity analyzed here) demonstrate little interaction with this protein and do not seem to affect collagen activity.
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Colágeno Tipo I/química , Dimetilpolisiloxanos/química , Prótesis e Implantes , Siloxanos/química , Dimetilpolisiloxanos/toxicidad , Estructura Molecular , Peso Molecular , Prótesis e Implantes/efectos adversos , Diseño de Prótesis , Agregado de Proteínas , Desnaturalización Proteica , Estabilidad Proteica , Estructura Secundaria de Proteína , Siloxanos/toxicidad , Relación Estructura-Actividad , Factores de Tiempo , ViscosidadRESUMEN
The goal was to develop a granule-type formulation, characterised as a long-term, zero-order release delivery system for doxorubicin hydrochloride (DOX) and composed of a sol-gel derived silica-polydimethylsiloxane solid matrix with well-defined microstructures. The preparation of the DOX-loaded granule-type formulation was performed using the sol-gel moulding method. A liquid-form of DOX was added to the sol before moulding. Optical microscopy, X-ray diffraction (XRD), Differential Scanning Calorimetry (DSC), Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), and N2 adsorption/desorption studies were employed to characterise the obtained formulation. The influence of different drug loads of DOX per granule (136, 336 and 555µg) on the release profiles was assessed on a USP Apparatus 4 dissolution and via UV/Vis end analysis. The in vitro mineralisation of these formulations associated with the nucleation of the apatite layer on their surface was also examined. The semi-ellipse shape and micrometer-size of the DOX-loaded granule-type formulation was successfully obtained. These formulations exhibited a mesoporous structure, uniform pore size distribution and good monodispersity. Following an initial burst, the slow drug release from all formulations followed zero order kinetics under infinite sink conditions for over 70days. Besides the formulation's potential properties as a carrier, the material was also surface-reactive during in vitro mineralisation.