RESUMEN
In this study, a novel quality assurance system was developed utilizing Process analytical technology (PAT) tools and artificial intelligence (AI). Our goal was to monitor the critical quality attributes (CQAs) like drug concentration, morphology and fiber diameter of electrospun amorphous solid dispersion (ASD) formulations with fast at-line techniques. Doxycycline-hyclate (DOX), a tetracycline-type antibiotic was used as a model drug with 2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD) as the matrix excipient. The water-based formulations were electrospun with high-speed electrospinning (HSES). Raman and NIR sensors and machine vision-based color measurement techniques were employed to accurately determine the drug concentration. Given that morphology can influence the solubility of the drug, a convolutional neural network (CNN)-based AI model was developed to examine this property and detect manufacturing defects. Additionally, the diameter of electrospun fibrous samples was measured using camera images and a trained AI model, enabling rapid analysis of fiber diameter with results similar to that of scanning electron microscopy (SEM). These methods and models demonstrate potential in-line analytical tools, offering rapid, cheap and non-destructive analysis of ASD formulations.
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Solubilidad , 2-Hidroxipropil-beta-Ciclodextrina/química , Química Farmacéutica/métodos , Excipientes/química , Composición de Medicamentos/métodos , Doxiciclina/química , Doxiciclina/análisis , Tecnología Farmacéutica/métodos , Microscopía Electrónica de Rastreo/métodos , Control de Calidad , Inteligencia Artificial , Antibacterianos/química , Antibacterianos/análisis , Redes Neurales de la Computación , Espectrometría Raman/métodosRESUMEN
In this study, a novel, sensitive, and cost-effective spectrofluorimetric approach was established for the estimation of two important tetracycline antibiotics, tetracycline and doxycycline, without any pre-treatment procedures or harsh reaction conditions, for the first time. The proposed methodology is based on the quantitative quenching effect of each tetracycline and doxycycline on the native fluorescence of nitrogen and sulfur co-doped carbon quantum dots (NS-CQDs). A simple and ultrafast approach was applied to synthesize NS-CQDs using thiosemicarbazide and citric acid as starting materials after incubation in a microwave for only 1 min. Utilizing an excitation wavelength of 360 nm, NS-CQDs showed maximum emission peak at 430 nm. Calibration curves revealed excellent linearity within the ranges of 1.0-10.0 and 0.8-12.0 µg/mL with detection limits of 0.20 and 0.09 µg/mL for tetracycline and doxycycline, respectively. Due to the method's high sensitivity and selectivity, the proposed approach was applied for the determination of the studied drugs in their capsules and human plasma samples with high %recoveries. The developed approach was validated according to ICHQ2(R2) guidelines. GAPI and AGREE metric tools were used to verify the method's greenness and eco-friendliness, suggesting its use as a green substitute for the analysis of the studied drugs.
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Antibacterianos , Carbono , Doxiciclina , Nitrógeno , Puntos Cuánticos , Espectrometría de Fluorescencia , Azufre , Tetraciclina , Puntos Cuánticos/química , Humanos , Carbono/química , Antibacterianos/sangre , Antibacterianos/análisis , Antibacterianos/química , Azufre/química , Nitrógeno/química , Tetraciclina/sangre , Tetraciclina/análisis , Tetraciclina/química , Doxiciclina/sangre , Doxiciclina/análisis , Doxiciclina/química , Colorantes Fluorescentes/química , Formas de Dosificación , Tecnología Química VerdeRESUMEN
In this report, a polytetrahydrofuran-coated polyester fabric phase sorptive extraction (FPSE) for the determination of doxycycline in human urine was described. The sol-gel polytetrahydrofuran sorbent proved to be superior against other sol-gel coated cellulose and polyester membranes tested. The effect of the extraction parameters including membrane surface area, sample pH and volume, salt concentration, extraction time, stirring rate, etc., on the extraction efficiency of the analyte was studied using the "one-factor-at-a-time" (OFAT) and Box-Behnken design approaches. The analytical method proposed was validated in compliance with FDA guidelines for bioanalytical procedures. The method was linear in the determination range of 100-5000 ng/mL with the determination coefficient of 0.9953. The limit of detection (LOD) and the lower limit of quantification for doxycycline was 17 and 100 ng/mL, respectively. The relative recoveries for intra-day and inter-day studies ranged from 98.5-112.2% and 89.6-96.8%, respectively. The relative standard deviation was lower than 14.7% in all cases, exhibiting good precision. The sol-gel polytetrahydrofuran-modified FPSE membranes were reusable for at least 30 times. The greenness of the developed method was evaluated using Sample Preparation Metric of Sustainability (SPMS) and Blue Applicability Grade Index (BAGI) metric tools. Finally, the analytical scheme was successfully employed for the quantitation of urinary doxycycline collected at various time points following the administration of doxycycline-containing tablets.
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Doxiciclina , Furanos , Poliésteres , Humanos , Doxiciclina/orina , Doxiciclina/química , Poliésteres/química , Furanos/orina , Furanos/química , Límite de Detección , Extracción en Fase Sólida/métodosRESUMEN
This research describes an easy, rapid, and inexpensive magnetic solid-phase extraction (MSPE) approach employing Fe3O4 magnetic nanoparticles modified with cetylpyridinium chloride (Fe3O4@CPC/MNPs) for extracting amoxicillin (AMX) and doxycycline (DOX) after derivatization with 4-chloroaniline as a color reagent. The azo-coupling of AMX and DOX with the color reagent in the alkaline medium caused yellow and yellow-orange azo dyes with maximum absorption wavelengths of 435 and 438 nm, respectively. The UV-Vis spectroscopy was utilized to determine the target analyte after the extraction procedure. Good linearities (R2 > 0.99) in the concentration ranges of 0.03-4.50 and 0.05-6.00 µg/mL were obtained for AMX and DOX, respectively. The experimental detection limits of AMX and DOX were obtained as 0.01 and 0.02 µg/mL, respectively. The developed approach was effectively applied to pre-concentrate and quantify AMX and DOX in environmental water and urine samples.
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Amoxicilina , Cetilpiridinio , Doxiciclina , Nanopartículas de Magnetita , Extracción en Fase Sólida , Contaminantes Químicos del Agua , Extracción en Fase Sólida/métodos , Amoxicilina/química , Amoxicilina/orina , Contaminantes Químicos del Agua/análisis , Cetilpiridinio/química , Doxiciclina/química , Doxiciclina/orina , Nanopartículas de Magnetita/química , Espectrofotometría , Monitoreo del Ambiente/métodos , Antibacterianos/orina , Antibacterianos/análisis , Antibacterianos/químicaRESUMEN
In this study, we successfully prepared palladium/agarose/copper foam (Pd/AG/CF) composite electrodes by utilizing the three-dimensional network structure agarose (AG), a green material derived from biomass, and homogeneously immobilizing palladium (Pd) atoms on a copper foam (CF) substrate through a facile route. The electrode showed excellent performance in the electrocatalytic degradation of doxycycline (DOX), with a high DOX degradation rate of 92.19 % in 60 min. In-depth studies revealed that palladium can form metal-metal interactions with the CF substrates, which enhances the electron transfer on the catalyst surface. In addition, the introduction of agarose effectively prevented the agglomeration of palladium nanoparticles. In addition, the hydroxyl functional groups in the molecular structure of agarose facilitate interactions between water molecules and the electrode interface through the formation of hydrogen bonds, thereby further enhancing the efficiency of the electrocatalytic reaction. In addition to good stability and reusability. Microbial toxicity test results show that the degraded wastewater has minimal impact on the environment. Also, possible degradation pathways of DOX were explored in this study. Finally, a novel continuous flow reactor was designed, featuring a unique design that ensures full contact between wastewater and the composite electrodes, thereby achieving continuous and efficient treatment of antibiotic wastewater.
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Cobre , Doxiciclina , Electrodos , Nanopartículas del Metal , Paladio , Sefarosa , Paladio/química , Cobre/química , Sefarosa/química , Catálisis , Nanopartículas del Metal/química , Doxiciclina/química , Contaminantes Químicos del Agua/química , Técnicas ElectroquímicasRESUMEN
Effective drug delivery to bacterially infected mucosa remains a challenge due to the combined obstacles of the mucosal barrier, pH variations, and high concentrations of glutathione. However, polysaccharide-based responsive nanogels (NGs) can take advantage of these conditions to deliver specific antimicrobials. We explored the critical features of pH- and redox-responsive NGs to increase drug penetration, residence time, and efficacy in the infected mucosa. We prepared multifunctional NGs using hydroxypropyl cellulose as a template for the cross-linking of methacrylic acid with N,N'-bis(acryloyl)cystamine (BAC) or N,N'-methylenebis(acrylamide) (BIS). Studies of NG-mucin binding and the antibacterial efficacy of doxycycline-loaded NGs revealed the interplay between the response to pH and redox clues. Specifically, higher BAC composition increased mucus binding and controlled release in reductive conditions, while higher BIS composition yielded NGs with higher doxycycline-mediated antibacterial efficacy against Staphylococcus aureus. The findings reveal the potential of multiresponsive NGs in effective antimicrobial delivery in infected mucosa.
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Nanogeles , Staphylococcus aureus , Staphylococcus aureus/efectos de los fármacos , Nanogeles/química , Animales , Sistemas de Liberación de Medicamentos/métodos , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/administración & dosificación , Membrana Mucosa/metabolismo , Doxiciclina/farmacología , Doxiciclina/química , Doxiciclina/administración & dosificación , Doxiciclina/farmacocinética , Celulosa/química , Celulosa/análogos & derivados , Polietilenglicoles/química , Concentración de Iones de Hidrógeno , Portadores de Fármacos/química , HumanosRESUMEN
Herein, it is demonstrated that 0D/2D design of zinc sulfide quantum dots encapsulated with yttrium tungstate nanosheets, which were subsequently used to increase the removal of brilliant blue (BB), methyl red (MR) dyes and doxycycline drug using UV-visible light. The produced ZnS-Y2WO6 nanohybrids exhibited excellent catalytic activity, reaching degradation efficiencies of around 89.92%, 80% and 85.51 % for BB, MR dyes and doxycycline drug, respectively, with a minimum irradiation duration of 120, 60 and 125 min. These nanohybrids outperformed Y2WO6 in terms of photocatalytic efficacy due to enhanced light absorption, efficient charge transfer, and decreased charge carrier recombination between ZnS and Y2WO6 nanoparticles. The synergistic combination of ZnS and Y2WO6 nanoparticles resulted in multiple active sites on the composite surface. Furthermore, the ZnS-Y2WO6 nanohybrids maintained excellent degradation efficiencies of 79.45% and 70.12% for BB and MR dyes, respectively, even after five consecutive cycles, with no significant loss of catalytic activity. The produced ZnS-Y2WO6 nanohybrids were thoroughly analyzed utilizing a variety of analytical methods. Furthermore, the degradation of organic dyes and doxycycline drug related possible mechanism were examined using experimental data, indicating the potential of ZnS-Y2WO6 nanohybrids as excellent photocatalytic materials for oxidizing organic dyes and drugs in aquatic conditions.
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Colorantes , Doxiciclina , Puntos Cuánticos , Sulfuros , Compuestos de Tungsteno , Itrio , Compuestos de Zinc , Sulfuros/química , Puntos Cuánticos/química , Compuestos de Zinc/química , Doxiciclina/química , Compuestos de Tungsteno/química , Itrio/química , Colorantes/química , Tamaño de la Partícula , Catálisis , Propiedades de Superficie , Contaminantes Químicos del Agua/aislamiento & purificación , Contaminantes Químicos del Agua/químicaRESUMEN
A novel smartphone-assisted fluorescent sensor based on europium/zirconium metal-organic framework (Eu0.5/Zr0.5-MOF) was developed for the fast and sensitive determination of doxycycline (DOX) and L-arginine (Arg). After the addition of DOX, the fluorescence of Eu0.5/Zr0.5-MOF was quenched owing to the inner filter effect (IFE). When Arg was introduced into the Eu0.5/Zr0.5-MOF@DOX complex system, the fluorescence was recovered because the interaction between Arg and Eu0.5/Zr0.5-MOF@DOX weakened the IFE. Moreover, the Eu0.5/Zr0.5-MOF produced continuous fluorescence color changes for the visual measurement of DOX and Arg. The fluorescent probe for DOX and Arg offered broad linear ranges of 0.05-80 and 0.1-60 µg/mL, respectively, with detection limits as low as 2.07 and 67.5 ng/mL. The proposed method was successfully applied to monitor DOX in eggs and Arg in human serum. This work provides a powerful platform for the real-time and visual analysis of DOX and Arg in food and biological samples.
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Arginina , Doxiciclina , Colorantes Fluorescentes , Teléfono Inteligente , Arginina/química , Arginina/análisis , Doxiciclina/análisis , Doxiciclina/química , Colorantes Fluorescentes/química , Humanos , Límite de Detección , Espectrometría de Fluorescencia/métodos , Huevos/análisis , Animales , Estructuras Metalorgánicas/química , Contaminación de Alimentos/análisis , FluorescenciaRESUMEN
The aim of this study was to examine the use of zwitterionic microparticles as new and efficient macromolecular supports for the sorption of an antibiotic (doxycycline hydrochloride, DCH) from aqueous solution. The effect of relevant process parameters of sorption, like dosage of microparticles, pH value, contact time, the initial concentration of drug and temperature, was evaluated to obtain the optimal experimental conditions. The sorption kinetics were investigated using Lagergren, Ho, Elovich and Weber-Morris models, respectively. The sorption efficiency was characterized by applying the Langmuir, Freundlich and Dubinin-Radushkevich isotherm models. The calculated thermodynamic parameters (ΔH, ΔS and ΔG) show that the sorption of doxycycline hydrochloride onto zwitterionic microparticles is endothermic, spontaneous and favorable at higher temperatures. The maximum identified sorption capacity value is 157.860 mg/g at 308 K. The Higuchi, Korsmeyer-Peppas, Baker-Lonsdale and Kopcha models are used to describe the release studies. In vitro release studies show that the release mechanism of doxycycline hydrochloride from zwitterionic microparticles is predominantly anomalous or non-Fickian diffusion. This study could provide the opportunity to expand the use of these new zwitterionic structures in medicine and water purification.
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Betaína , Doxiciclina , Doxiciclina/química , Betaína/química , Cinética , Adsorción , Termodinámica , Concentración de Iones de Hidrógeno , Antibacterianos/química , Liberación de Fármacos , Temperatura , MicroesferasRESUMEN
Sensor array methods have received much attention in recent years. In this study, a colorimetric sensor array consisting of three kinds of steel slag-based composites (including porphyrin-functionalized non-magnetic steel slag (NMSS-Por), alkali-excited steel slag (A-SS), and platinum modified steel slag (ALANH-Pt)) was developed for the detection and recognition of tetracycline antibiotics (TCs) such as tetracycline (TC), oxytetracycline (OTC) and doxycycline (DOX). Linear discriminant analysis (LDA) and hierarchical cluster analysis (HCA) showed that the colorimetric sensor array has excellent recognition ability for TCs. The detection limits of this sensor array for TC, OTC, and DOX were 0.059 µM, 0.111 µM and 0.118 µM, respectively, which provided higher sensitivity compared to the colorimetric sensors composed of a single steel slag-based composite material. At the same time, the array sensor has anti-interference ability, and this study provides a new application route for steel slag.
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Antibacterianos , Colorimetría , Acero , Colorimetría/métodos , Colorimetría/instrumentación , Acero/química , Antibacterianos/análisis , Límite de Detección , Tetraciclina/análisis , Tetraciclina/química , Tetraciclinas/análisis , Doxiciclina/análisis , Doxiciclina/química , Análisis DiscriminanteRESUMEN
This study constructed bilayer nano-hydrogels using solvent casting and electrospinning techniques. The first layer consisted of a hydrogel containing sodium alginate and gellan gum, while the second layer was a carrageenan/polyvinyl alcohol nanofibrous membrane. The nanohydrogels were prepared with different doses of doxycycline antibiotic (0.12, 0.06, 0.03 g) and a fixed amount of silver nanoparticles (0.012 g), which were synthesized using the green method including Capparis spinosa leaf extract. The films were tested for their mechanical properties, swelling behavior, XRD, and FTIR, and their morphology was characterized using SEM. The biological properties of the nanohydrogels were also extensively assayed. X-ray diffraction analysis showed peak 111 for silver nanoparticles. Incorporating silver nanoparticles significantly enhanced nanohydrogels' mechanical and antibacterial properties and improved their ability to heal wounds. Nanohydrogels exhibited biodegradability, biocompatibility, anti-inflammatory properties (57.63 %), and high cell viability (>85 %) in laboratory conditions. The study confirmed that wound dressings containing doxycycline with controlled release are highly effective against pathogenic bacteria and prevent the formation of biofilms (92 %). The rats in-vivo study demonstrated that 100 % wound closure was achieved in nanohydrogels containing SA/GG/PVA/CAR/AgNPs/DOX0.12 after 14 days. The films could potentially lead to the development of new treatments against bacterial infections and inflammatory conditions of wounds.
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Alginatos , Antibacterianos , Carragenina , Hidrogeles , Nanopartículas del Metal , Nanofibras , Plata , Infección de Heridas , Plata/química , Carragenina/química , Alginatos/química , Antibacterianos/farmacología , Antibacterianos/química , Nanofibras/química , Hidrogeles/química , Hidrogeles/farmacología , Animales , Nanopartículas del Metal/química , Ratas , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/microbiología , Cicatrización de Heridas/efectos de los fármacos , Doxiciclina/farmacología , Doxiciclina/química , Tecnología Química VerdeRESUMEN
Currently, postoperative infection is a significant challenge in bone and dental surgical procedures, demanding the exploration of innovative approaches due to the prevalence of antibiotic-resistant bacteria. This study aims to develop a strategy for controlled and smart antibiotic release while accelerating osteogenesis to expedite bone healing. In this regard, temperature-responsive doxycycline (DOX) imprinted bioglass microspheres (BGMs) were synthesized. Following the formation of chitosan-modified BGMs, poly N-isopropylacrylamide (pNIPAm) was used for surface imprinting of DOX. The temperature-responsive molecularly imprinted polymers (MIPs) exhibited pH and temperature dual-responsive adsorption and controlled-release properties for DOX. The temperature-responsive MIP was optimized by investigating the molar ratio of N,N'-methylene bis(acrylamide) (MBA, the cross-linker) to NIPAm. Our results demonstrated that the MIPs showed superior adsorption capacity (96.85 mg/g at 35 °C, pH = 7) than nonimprinted polymers (NIPs) and manifested a favorable selectivity toward DOX. The adsorption behavior of DOX on the MIPs fit well with the Langmuir model and the pseudo-second-order kinetic model. Drug release studies demonstrated a controlled release of DOX due to imprinted cavities, which were fitted with the Korsmeyer-Peppas kinetic model. DOX-imprinted BGMs also revealed comparable antibacterial effects against Staphylococcus aureus and Escherichia coli to the DOX (control). In addition, MIPs promoted viability and osteogenic differentiation of MG63 osteoblast-like cells. Overall, the findings demonstrate the significant potential of DOX-imprinted BGMs for use in bone defects. Nonetheless, further in vitro investigations and subsequent in vivo experiments are warranted to advance this research.
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Antibacterianos , Cerámica , Doxiciclina , Microesferas , Osteogénesis , Staphylococcus aureus , Doxiciclina/farmacología , Doxiciclina/química , Antibacterianos/farmacología , Antibacterianos/química , Cerámica/química , Cerámica/farmacología , Staphylococcus aureus/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Humanos , Impresión Molecular , Escherichia coli/efectos de los fármacos , Liberación de Fármacos , Quitosano/química , Quitosano/farmacologíaRESUMEN
Nowadays, electrospun fibrous mats are used as drug delivery systems for loading of potential drugs in order to kill cancer cells. In the study, a skin patch for treating melanoma cancer after surgery was made using polycaprolactone and polymetformin microfibers that were loaded with doxycycline (PolyMet/PCL@DOX), an anti-cancer stem cell agent. The morphology, structure, mechanical characteristics, swelling, and porosity of the electrospun microfibers were examined. Drug release andanticancereffectiveness of PolyMet/PCL@DOXwas evaluated against A375 melanoma cancer stem cells using the MTS, Flow cytometry, colony formation and CD44 expression assays. Scanning electron microscopy (SEM) verified the micro fibrous structure with a diameter of about 2.31 µm. The porosity and swelling percentages for microfibers was 73.5 % and 2.9 %, respectively. The tensile strength at the breaking point was equal to 3.84 MPa. The IC50 of PolyMet/PCL@DOX was 7.4 µg/mL. The survival rate of A375 cells after 72 h of PolyMet/PCL@DOX treatment was 43.9 %. The colony formation capacity of A375 cells decreased after PolyMet/PCL@DOX treatment. The level of CD44 expression in the PolyMet/PCL@DOX group decreased compared to the control group. Generally, PolyMet/PCL@DOX microfibers can be a promising candidate as a patch after surgery to eradicate cancer stem cells, effectively.
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Doxiciclina , Liberación de Fármacos , Melanoma , Células Madre Neoplásicas , Poliésteres , Doxiciclina/administración & dosificación , Doxiciclina/farmacología , Doxiciclina/química , Poliésteres/química , Humanos , Melanoma/tratamiento farmacológico , Melanoma/patología , Células Madre Neoplásicas/efectos de los fármacos , Línea Celular Tumoral , Metformina/farmacología , Metformina/administración & dosificación , Metformina/química , Supervivencia Celular/efectos de los fármacos , Receptores de Hialuranos/metabolismo , Porosidad , Sistemas de Liberación de Medicamentos/métodos , Portadores de Fármacos/química , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacología , Antineoplásicos/químicaRESUMEN
BACKGROUND: Chronic rhinosinusitis (CRS) is an inflammatory disease affecting the sinuses or nose. Persistent inflammatory responses can lead to tissue remodeling, which is a pathological characteristics of CRS. Activation of fibroblasts in the nasal mucosal stroma, differentiation and collagen deposition, and subepithelial fibrosis have been associated with CRS. OBJECTIVES: We aimed to assess the inhibitory effects of doxycycline and deoxycholic acid-polyethyleneimine conjugate (DA3-Doxy) on myofibroblast differentiation and extracellular matrix (ECM) production in nasal fibroblasts stimulated with TGF-ß1. METHODS: To enhance efficacy, we prepared DA3-Doxy using a conjugate of low-molecular-weight polyethyleneimine (PEI) (MW 1800) and deoxycholic acid (DA) and Doxy. The synthesis of the DA3-Doxy polymer was confirmed using nuclear magnetic resonance, and the critical micelle concentration required for cationic micelle formation through self-assembly was determined. Subsequently, the Doxy loading efficiency of DA3 was assessed. The cytotoxicity of Doxy, DA3, PEI, and DA-Doxy in nasal fibroblasts was evaluated using the WST-1 assay. The anti-tissue remodeling and anti-inflammatory effects of DA3-Doxy and DA3 were examined using real-time polymerase chain reaction (Real-time PCR), immunocytochemistry, western blot, and Sircol assay. RESULTS: Both DA3 and DA3-Doxy exhibited cytotoxicity at 10 µg/ml in nasal fibroblasts. Doxy partially inhibited α-smooth muscle actin, collagen types I and III, and fibronectin. However, DA3-Doxy significantly inhibited α-SMA, collagen types I and III, and fibronectin at 5 µg/ml. DA3-Doxy also modulated TGF-ß1-induced changes in the expression of MMP 1, 2, and 9. Nonetheless, TGF-ß1-induced expression of MMP3 was further increased by DA3-Doxy. The expression of TIMP 1 and 2 was partially reduced with 5 µg/ml DA3-Doxy. CONCLUSIONS: Although initially developed for the delivery of genetic materials or drugs, DA3 exhibits inhibitory effects on myofibroblast differentiation and ECM production. Therefore, it holds therapeutic potential for CRS, and a synergistic effect can be expected when loaded with CRS treatment drugs.
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Diferenciación Celular , Ácido Desoxicólico , Doxiciclina , Fibroblastos , Polietileneimina , Humanos , Polietileneimina/química , Polietileneimina/farmacología , Ácido Desoxicólico/química , Ácido Desoxicólico/farmacología , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Diferenciación Celular/efectos de los fármacos , Doxiciclina/farmacología , Doxiciclina/química , Matriz Extracelular/metabolismo , Matriz Extracelular/efectos de los fármacos , Factor de Crecimiento Transformador beta1/metabolismo , Miofibroblastos/efectos de los fármacos , Miofibroblastos/metabolismo , Mucosa Nasal/efectos de los fármacos , Mucosa Nasal/metabolismo , Mucosa Nasal/citología , Actinas/metabolismoRESUMEN
The development of antibiotic-loaded microneedles has been hindered for years by limited excipient options, restricted drug-loading space, poor microneedle formability, and short-term drug retention. Therefore, this study proposes a dissolving microneedle fabricated from the host-defense peptide ε-poly-l-lysine (EPL) as an antibacterial adjuvant system for delivering antibiotics. EPL serves not only as a major matrix material for the microneedle tips, but also as a broad-spectrum antibacterial agent that facilitates the intracellular accumulation of the antibiotic doxycycline (DOX) by increasing bacterial cell membrane permeability. Furthermore, the formation of physically crosslinked networks of EPL affords microneedle tips with improved formability, good mechanical properties, and amorphous nanoparticles (approximately 7.2 nm) of encapsulated DOX. As a result, a high total loading content of both antimicrobials up to 2319.1 µg/patch is achieved for efficient transdermal drug delivery. In a Pseudomonas aeruginosa-induced deep cutaneous infection model, the EPL microneedles demonstrates potent and long-term effects by synergistically enhancing antibiotic activities and prolonging drug retention in infected lesions, resulting in remarkable therapeutic efficacy with 99.91 % (3.04 log) reduction in skin bacterial burden after a single administration. Overall, our study highlights the distinct advantages of EPL microneedles and their potential in clinical antibacterial practice when loaded with amorphous DOX nanoparticles.
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Antibacterianos , Doxiciclina , Nanopartículas , Agujas , Polilisina , Polilisina/química , Doxiciclina/administración & dosificación , Doxiciclina/farmacología , Doxiciclina/química , Nanopartículas/química , Antibacterianos/farmacología , Antibacterianos/administración & dosificación , Antibacterianos/química , Animales , Pseudomonas aeruginosa/efectos de los fármacos , Ratones , Sistemas de Liberación de Medicamentos , Administración Cutánea , Piel/efectos de los fármacos , Piel/microbiología , Infecciones por Pseudomonas/tratamiento farmacológicoRESUMEN
The development of high-performance sensors for doxycycline (DOX) detection is necessary because its residue accumulation will cause serious harm to human health and the environment. Here, a novel tri-emission ratiometric fluorescence sensor was proposed by using "post-mixing" strategy of different emissions fluorescence molecularly imprinted polymers with salicylamide as dummy template (DMIPs). BSA was chosen as assistant functional monomer, and also acted as sensitizers for the aggregation-induced emission (AIE) effect of DOX. The blue-emitting carbon dots and the red-emitting CdTe quantum dots were separately introduced into DMIPs as the response signals. Upon DOX recognition within 2 min, blue and red fluorescence of the tri-emission DMIPs sensor were quenched while green fluorescence of DOX was enhanced, resulting in a wide range of color variations observed over bluish violet-rosered-light pink-orange-yellow-green with a detection limit of 0.061 µM. The sensor possessed highly selective recognition and was successfully applied to detect DOX in complicated real samples. Moreover, with the fluorescent color collection and data processing, the smartphone-assisted visual detection of the sensors showed satisfied sensitivity with low detection limit. This work provides great potential applications for rapid and visual detection of antibiotics in complex substrates.
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Antibacterianos , Compuestos de Cadmio , Doxiciclina , Impresión Molecular , Puntos Cuánticos , Espectrometría de Fluorescencia , Telurio , Doxiciclina/análisis , Doxiciclina/química , Puntos Cuánticos/química , Telurio/química , Antibacterianos/análisis , Compuestos de Cadmio/química , Límite de Detección , Fluorescencia , Carbono/química , Colorantes Fluorescentes/química , Polímeros Impresos Molecularmente/química , Teléfono InteligenteRESUMEN
Doxycycline, a semi-synthetic tetracycline, is a widely used antibiotic for treating mild-to-moderate infections, including skin problems. However, its anti-inflammatory and antioxidant properties, combined with its ability to interfere with α-synuclein aggregation, make it an attractive candidate for repositioning in Parkinson's disease. Nevertheless, the antibiotic activity of doxycycline restricts its potential use for long-term treatment of Parkinsonian patients. In the search for non-antibiotic tetracyclines that could operate against Parkinson's disease pathomechanisms, eighteen novel doxycycline derivatives were designed. Specifically, the dimethyl-amino group at C4 was reduced, resulting in limited antimicrobial activity, and several coupling reactions were performed at position C9 of the aromatic D ring, this position being one of the most reactive for introducing substituents. Using the Thioflavin-T assay, we found seven compounds were more effective than doxycycline in inhibiting α-synuclein aggregation. Furthermore, two of these derivatives exhibited better anti-inflammatory effects than doxycycline in a culture system of microglial cells used to model Parkinson's disease neuroinflammatory processes. Overall, through structure-activity relationship studies, we identified two newly designed tetracyclines as promising drug candidates for Parkinson's disease treatment.
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Doxiciclina , Enfermedad de Parkinson , Agregado de Proteínas , alfa-Sinucleína , Humanos , alfa-Sinucleína/metabolismo , alfa-Sinucleína/antagonistas & inhibidores , Relación Dosis-Respuesta a Droga , Doxiciclina/farmacología , Doxiciclina/química , Estructura Molecular , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/farmacología , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/metabolismo , Agregado de Proteínas/efectos de los fármacos , Relación Estructura-ActividadRESUMEN
The ubiquity and impact of pharmaceuticals and pesticides, as well as their residues in environmental compartments, particularly in water, have raised human and environmental health concerns. This emphasizes the need of developing sustainable methods for their removal. Solar-driven photocatalytic degradation has emerged as a promising approach for the chemical decontamination of water, sparking intensive scientific research in this field. Advancements in photocatalytic materials have driven the need for solar reactors that efficiently integrate photocatalysts for real-world water treatment. This study reports preliminary results from the development and evaluation of a solar system for TiO2-based photocatalytic degradation of intermittently flowing water contaminated with doxycycline (DXC), sulfamethoxazole (SMX), dexamethasone (DXM), and carbendazim (CBZ). The system consisted of a Fresnel-type UV solar concentrator that focused on the opening and focal point of a parabolic trough concentrator, within which tubular quartz glass reactors were fixed. Concentric springs coated with TiO2, arranged one inside the other, were fixed inside the quartz reactors. The reactors are connected to a raw water tank at the inlet and a check valve at the outlet. Rotating wheels at the collector base enable solar tracking in two axes. The substances (SMX, DXC, and CBZ) were dissolved in dechlorinated tap water at a concentration of 1.0 mg/L, except DXM (0.8 mg/L). The water underwent sequential batch (~ 3 L each, without recirculation) processing with retention times of 15, 30, 60, 90, and 120 min. After 15 min, the degradation rates were as follows: DXC 87%, SMX 35.5%, DXM 32%, and CBZ 31.8%. The system processed 101 L of water daily, simultaneously removing 870, 355, 256, and 318 µg/L of DXC, SMX, DXM, and CBZ, respectively, showcasing its potential for real-world chemical water decontamination application. Further enhancements that enable continuous-flow operation and integrate highly effective adsorbents and photocatalytic materials can significantly enhance system performance.
Asunto(s)
Fotoquímica , Energía Solar , Contaminantes Químicos del Agua , Purificación del Agua , Agua , Catálisis/efectos de la radiación , Agua/química , Purificación del Agua/instrumentación , Purificación del Agua/métodos , Humanos , Contaminantes Químicos del Agua/química , Contaminantes Químicos del Agua/aislamiento & purificación , Doxiciclina/química , Doxiciclina/aislamiento & purificación , Sulfametoxazol/química , Sulfametoxazol/aislamiento & purificación , Dexametasona/química , Dexametasona/aislamiento & purificación , Cuarzo , Cromatografía , Temperatura , Factores de Tiempo , Animales , Abastecimiento de AguaRESUMEN
Bacterial pneumonia is one of the major threats in clinical practice, and the reactive oxygen species (ROS) generated at the infection site can exacerbate the damage. Currently, conventional antibiotic therapies have low utilization, and their excessive use can result in substantial toxicity. Nanocarrier systems provide an ideal approach for treating bacterial infection by facilitating more efficient utilization of antibiotics. In this study, the ROS-responsive amphiphilic nanoparticles (NPs) are developed and used to encapsulate the antibiotic doxycycline (DOXY) to achieve antibacterial and antioxidant functionalities. The NPs are prepared from poly(α-l-lysine) (α-PLL) and phenylboronic acid pinacol ester simultaneously conjugated carbonyldiimidazole (abbreviated as CDIPB). The phenylboronic acid ester groups on CDIPB could react with excessive ROS to suppress oxidative damage at the infection site. The ROS-responsive degradation of CDIPB also facilitates the rapid release of internal DOXY, effectively killing the accumulated bacteria. Additionally, in vitro cell experiments demonstrate the good biocompatibility of the NPs. These results suggest that the ROS-responsive amphiphilic nanoparticles can serve as a novel nanoplatform for the treatment of bacterial pneumonia.
Asunto(s)
Antibacterianos , Doxiciclina , Nanopartículas , Estrés Oxidativo , Polilisina , Especies Reactivas de Oxígeno , Polilisina/química , Polilisina/farmacología , Especies Reactivas de Oxígeno/metabolismo , Doxiciclina/farmacología , Doxiciclina/química , Nanopartículas/química , Estrés Oxidativo/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Animales , Humanos , Ratones , Portadores de Fármacos/química , Antioxidantes/farmacología , Antioxidantes/químicaRESUMEN
Antibiotic administration is an adjacent therapy to guided tissue regeneration (GTR) in the management of periodontitis. This is due to the major role of pathogen biofilm in aggravating periodontal defects. This study aimed to fabricate a GTR membrane for sustained delivery of doxycycline hydrochloride (DOX) while having a space-maintaining function. The membranes were prepared using a polymeric blend of polycaprolactone/polyvinyl alcohol/chitosan by the electrospinning technique. The obtained membranes were characterized in terms of physicochemical and biological properties. Nanofibers showed a mean diameter in the submicron range of < 450 nm while having uniform randomly aligned morphology. The obtained membranes showed high strength and flexibility. A prolonged in vitro release profile during 68 h was observed for manufactured formulations. The prepared membranes showed a cell viability of > 70% at different DOX concentrations. The formulations possessed antimicrobial efficacy against common pathogens responsible for periodontitis. In vivo evaluation also showed prolonged release of DOX for 14 days. The histopathological evaluation confirmed the biocompatibility of the GTR membrane. In conclusion, the developed nanofibrous DOX-loaded GTR membranes may have beneficial characteristics in favour of both sustained antibiotic delivery and periodontal regeneration by space-maintaining function without causing any irritation and tissue damage.