ABSTRACT
Immediate control of excessive bleeding and prevention of infections are of utmost importance in the management of wounds. Cryogels have emerged as promising materials for the rapid release of medication and achieving hemostasis. However, their quick release properties pose the challenge of exposing patients to high concentrations of drugs. In this study, hybrid nanocomposites were developed to address this issue by combining poly(vinyl alcohol) and κ-carrageenan with whitlockite nanoapatite (WNA) particles and ciprofloxacin, aiming to achieve rapid hemostasis and sustained antibacterial effects. A physically cross-linked cryogel was obtained by subjecting a blend of poly(vinyl alcohol) and κ-carrageenan to successive freezing-thawing cycles, followed by the addition of WNA. Furthermore, ciprofloxacin was introduced into the cryogel matrix for subsequent evaluation of its wound healing properties. The resulting gel system exhibited a 3D microporous structure and demonstrated excellent swelling, low cytotoxicity, and outstanding mechanical properties. These characteristics were evaluated through analytical and rheological experiments. The nanocomposite cryogel with 4% whitlockite showed extended drug release of 71.21 ± 3.5% over 21 days and antibacterial activity with a considerable growth inhibition zone (4.19 ± 3.55 cm). Experiments on a rat model demonstrated a rapid hemostasis property of cryogels within an average of 83 ± 4 s and accelerated the process of wound healing with 96.34% contraction compared to the standard, which exhibited only â¼78% after 14 days. The histopathological analysis revealed that the process of epidermal re-epithelialization took around 14 days following the skin incision. The cryogel loaded with WNAs and ciprofloxacin holds great potential for strategic utilization in wound management applications as an effective material for hemostasis and anti-infection purposes.
Subject(s)
Calcium Phosphates , Cryogels , Polyvinyl Alcohol , Humans , Rats , Animals , Cryogels/chemistry , Polyvinyl Alcohol/pharmacology , Carrageenan/chemistry , Wound Healing , Ciprofloxacin , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Hemostasis , EthanolABSTRACT
Carrier-based polymeric membrane potentiometric sensors are an ideal tool for detecting ionic species. However, in the fabrication of these sensors, the screening of carriers still relies on empirical trial- and error-based optimization, which requires tedious and time-consuming experimental verification. In this work, computer-aided screening of carriers is applied in the preparation of polymeric membrane potentiometric sensors. Molecular docking is used to study the host-guest interactions between receptors and targets. Binding energies are employed as the standard to screen the appropriate carrier. As a proof-of-concept experiment, the antibiotic ciprofloxacin is selected as the target model. A series of supramolecular macrocyclic receptors including cyclodextrins, cucurbiturils and calixarenes are chosen as potential receptors. The proposed sensor based on the receptor calix[4]arene screened by molecular docking shows a lower detection limit of 0.5 µmol L-1 for ciprofloxacin. It can be expected that the proposed computer-aided screening technique of carriers can provide a simple but highly efficient method for the fabrication of carrier-based electrochemical and optical sensors.
Subject(s)
Calixarenes , Macrocyclic Compounds , Anti-Bacterial Agents , Molecular Docking Simulation , Potentiometry , Macrocyclic Compounds/chemistry , Polymers/chemistry , Calixarenes/chemistry , CiprofloxacinABSTRACT
The present case reports a bacteremia due to Lachnoanaerobaculum umeaense (a Gram-positive, filamentous, rod-shaped, anaerobic, spore-forming bacillus present in the human oral microbiota) in a patient treated for acute myeloid leukemia. After failed identification by MALDI-TOF, identification was done by sequencing of 16s rRNA. The patient was successfully treated with Amoxicillin-clavulanic acid and ciprofloxacin for seven days. Comparison of V1-V3 regions of the bacterial 16S rRNA gene gene with published sequences failed to classify the strain as pathogenic or non-pathogenic based on this phylogenetic classification alone. Although Lachnoanaerobaculum gingivalis are known to be associated with bacteremia in patients with acute myeloid leukemia, this clinical case of infection by L. umeaense argues for further studies that will lead to more efficient classification of the infection by these microorganisms.
Subject(s)
Anti-Bacterial Agents , Bacteremia , Leukemia, Myeloid, Acute , RNA, Ribosomal, 16S , Humans , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/complications , Bacteremia/microbiology , Bacteremia/drug therapy , Bacteremia/diagnosis , RNA, Ribosomal, 16S/genetics , Anti-Bacterial Agents/therapeutic use , Male , Gram-Positive Bacterial Infections/drug therapy , Gram-Positive Bacterial Infections/microbiology , Gram-Positive Bacterial Infections/diagnosis , Phylogeny , Ciprofloxacin/therapeutic use , Middle Aged , Amoxicillin-Potassium Clavulanate Combination/therapeutic useABSTRACT
The leaching of additives from plastics and elastomers (rubbers) has raised concerns due to their potential negative impacts on the environment and the development of antibiotic resistance. In this study, we investigated the effects of chemicals extracted from two types of rubber on microbiomes derived from a benthic sea urchin and two pelagic fish species. Additionally, we examined whether bacterial communities preconditioned with rubber-associated chemicals displayed adaptations to antibiotics. At the highest tested concentrations of chemicals, we observed reduced maximum growth rates and yields, prolonged lag phases, and increased alpha diversity. While the effects on alpha and beta diversity were not always conclusive, several bacterial genera were significantly influenced by chemicals from the two rubber sources. Subsequent exposure of sea urchin microbiomes preconditioned with rubber chemicals to the antibiotic ciprofloxacin resulted in decreased maximum growth rates. This indicates a more sensitive microbiome to ciprofloxacin when preconditioned with rubber chemicals. Although no significant interaction effects between rubber chemicals and ciprofloxacin exposure were observed in bacterial alpha and beta diversity, we observed log-fold changes in two bacterial genera in response to ciprofloxacin exposure. These findings highlight the structural and functional alterations in microbiomes originating from various marine species when exposed to rubber-associated chemicals and underscore the potential risks posed to marine life.
Subject(s)
Microbiota , Rubber , Animals , Anti-Bacterial Agents/toxicity , Plastics , Ciprofloxacin/toxicityABSTRACT
Curcumin is a natural compound that is considered safe and may have potential health benefits; however, its poor stability and water insolubility limit its therapeutic applications. Different strategies aim to increase its water solubility. Here, we tested the compound PVP-curcumin as a photosensitizer for antimicrobial photodynamic therapy (aPDT) as well as its potential to act as an adjuvant in antibiotic drug therapy. Gram-negative E. coli K12 and Gram-positive S. capitis were subjected to aPDT using various PVP-curcumin concentrations (1-200 µg/mL) and 475 nm blue light (7.5-45 J/cm2). Additionally, results were compared to aPDT using 415 nm blue light. Gene expression of recA and umuC were analyzed via RT-qPCR to assess effects on the bacterial SOS response. Further, the potentiation of Ciprofloxacin by PVP-curcumin was investigated, as well as its potential to prevent the emergence of antibiotic resistance. Both bacterial strains were efficiently reduced when irradiated with 415 nm blue light (2.2 J/cm2) and 10 µg/mL curcumin. Using 475 nm blue light, bacterial reduction followed a biphasic effect with higher efficacy in S. capitis compared to E. coli K12. PVP-curcumin decreased recA expression but had limited effect regarding enhancing antibiotic treatment or impeding resistance development. PVP-curcumin demonstrated effectiveness as a photosensitizer against both Gram-positive and Gram-negative bacteria but did not modulate the bacterial SOS response.
Subject(s)
Anti-Bacterial Agents , Ciprofloxacin , Curcumin , Photosensitizing Agents , Rec A Recombinases , Curcumin/pharmacology , Photosensitizing Agents/pharmacology , Rec A Recombinases/metabolism , Rec A Recombinases/genetics , Ciprofloxacin/pharmacology , Anti-Bacterial Agents/pharmacology , Photochemotherapy/methods , SOS Response, Genetics/drug effects , Escherichia coli K12/drug effects , Escherichia coli K12/genetics , Escherichia coli Proteins/metabolism , Escherichia coli Proteins/genetics , Povidone/chemistry , Povidone/pharmacology , Microbial Sensitivity Tests , Escherichia coli/drug effects , Light , DNA-Binding ProteinsABSTRACT
Short-term influence of polytetrafluoroethylene micro/nano-plastics (PTFE-MPs/NPs) on the inhibition of copper (Cu2+) and/or ciprofloxacin (CIP) on the nitrifying sludge activities was explored based on concentration addition (CA) and independent action (IA) models. The half maximal inhibitory concentration (IC50) of Cu2+, CIP, PTFE-MPs (3 µm), and PTFE-NPs (800 nm) on the specific ammonium oxidation rate (SAOR) of nitrifying sludge was 64.57, 51.29, 102.33 and 93.33 mg L-1, respectively, while those on the specific nitrite oxidation rate (SNOR) of nitrifying sludge were 77.62, 32.36, 104.70 and 97.72 mg L-1, respectively. Among the five binary mixtures and two ternary mixtures composed by Cu2+, CIP, and/or PTFE-MPs/NPs, it was found that the two joint inhibitory actions from ternary mixtures on the SAOR and SNOR of the sludge showed time-dependent characteristics by analyzing of CA and IA models, while the five combined inhibitory effects from different binary mixtures did not all have time-dependent features. The two joint inhibition actions from diverse ternary mixtures on the SAOR at the exposure time of 60 min and on the SNOR at 90 min showed always concentration-dependent features, while the combined inhibitions with concentration-dependent characteristics had never been observed in the binary Cu2+ and PTFE-NPs mixtures at different exposure time. The Cu2+, CIP, and PTFE-MPs mixtures (or Cu2+, CIP, and PTFE-NPs mixtures) had synergistic actions on the SAOR at 90 min and antagonistic effects on the SNOR at 60 min based on CA and IA models, and these combined inhibitions did not exhibit concentration-dependent characteristics. In contrast, the joint inhibitory effects (on the SAOR and SNOR) with concentration-dependent features were found in the binary mixtures of CIP and PTFE-MPs at different exposure time, and the join inhibition changed from synergism to antagonism as the increasing concentration of mixed CIP and PTFE-MPs. This study provides novel perspectives for understanding the combined influence of plastic particles with different sizes, antibiotics, and heavy metals on the biological wastewater treatment process.
Subject(s)
Ciprofloxacin , Copper , Ciprofloxacin/pharmacology , Sewage , Microplastics , PolytetrafluoroethyleneABSTRACT
Interactions of microplastics (MPs) biofilm with antibiotic resistance genes (ARGs) and antibiotics in aquatic environments have made microplastic biofilm an issue of keen scholarly interest. The process of biofilm formation and the degree of ARGs enrichment in the presence of antibiotic-selective pressure and the impact on the microbial community need to be further investigated. In this paper, the selective pressure of ciprofloxacin (CIP) and illumination conditions were investigated to affect the physicochemical properties, biomass, and extracellular polymer secretion of polyvinyl chloride (PVC) microplastic biofilm. In addition, relative copy numbers of nine ARGs were analyzed by real-time quantitative polymerase chain reaction (qPCR). In the presence of CIP, microorganisms in the water and microplastic biofilm were more inclined to carry associated ARGs (2-3 times higher), which had a contributing effect on ARGs enrichment. The process of pre-microplastic biofilm formation might have an inhibitory effect on ARGs (total relative abundance up to 0.151) transfer and proliferation compared to the surrounding water (total relative abundance up to 0.488). However, in the presence of CIP stress, microplastic biofilm maintained the abundance of ARGs (from 0.151 to 0.149) better compared to the surrounding water (from 0.488 to 0.386). Therefore, microplastic biofilm act as abundance buffer island of ARGs stabilizing the concentration of ARGs. In addition, high-throughput analyses showed the presence of antibiotic-resistant (Pseudomonas) and pathogenic (Vibrio) microorganisms in biofilm under different conditions. The above research deepens our understanding of ARGs enrichment in biofilm and provides important insights into the ecological risks of interactions between ARGs, antibiotics, and microplastic biofilm.
Subject(s)
Microplastics , Plastics , Genes, Bacterial , Rivers , Anti-Bacterial Agents/pharmacology , Drug Resistance, Microbial/genetics , Ciprofloxacin , Water , BiofilmsABSTRACT
Microplastics (MPs), as emerging contaminants, usually experience aging processes in natural environments and further affect their interactions with coexisted contaminants, resulting in unpredictable ecological risks. Herein, the effect of MPs aging on their adsorption for coexisting antibiotics and their joint biotoxicity have been investigated. Results showed that the adsorption capacity of aged polystyrene (PS, 100 d and 50 d) for ciprofloxacin (CIP) was 1.10-4.09 times higher than virgin PS due to the larger BET surface area and increased oxygen-containing functional groups of aged PS. Following the increased adsorption capacity of aged PS, the joint toxicity of aged PS and CIP to Shewanella Oneidensis MR-1 (MR-1) was 1.03-1.34 times higher than virgin PS and CIP. Combined with the adsorption process, CIP posed higher toxicity to MR-1 compared to aged PS due to the rapid adsorption of aged PS for CIP in the first 12 h. After that, the adsorption process tended to be gentle and hence the joint toxicity to MR-1 was gradually dominated by aged PS. A similar transformation between the adsorption rate and the joint toxicity of PS and CIP was observed under different conditions. This study supplied a novel perception of the synergistic effects of PS aging and CIP on ecological health.
Subject(s)
Ciprofloxacin , Polystyrenes , Shewanella , Ciprofloxacin/chemistry , Ciprofloxacin/toxicity , Polystyrenes/toxicity , Polystyrenes/chemistry , Adsorption , Shewanella/drug effects , Microplastics/toxicity , Microplastics/chemistry , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/toxicity , Water Pollutants, Chemical/toxicity , Water Pollutants, Chemical/chemistryABSTRACT
AIM: 3Mixtatin (a combination of Metronidazole, Minocycline, and Ciprofloxacin along with statins) is a novel biomaterial in pulp therapy, while Mineral Trioxide Aggregate (MTA) is considered the gold standard in endodontics. This study aimed to compare the clinical and radiographic success rates of MTA and 3Mixtatin in pulp therapy of primary teeth. METHODS AND MATERIALS: MEDLINE (PubMed), CENTRAL, Web of Science, Scopus, ProQuest databases, and Google Scholar were searched to identify randomized controlled trials (RCTs) on pulp therapy with 3Mixtatin and MTA in primary teeth, published up to February 2023. It should be noted that the protocol was previously registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD42021243626). RCTs were assessed independently by two researchers in terms of eligibility and quality. Data extracted and tabulated. The Cochrane Risk of Bias (RoB-2) tool was used to assess the risk of bias. The effect sizes were evaluated utilizing risk ratios (RRs). The heterogeneity investigation was conducted utilizing I² measurement at α = 0.10. RESULTS: Out of 86 retrieval records, four articles met the inclusion criteria. Based on clinical and radiographic outcomes, the application of 3Mixtatin in the pulp therapy of primary teeth was as successful as MTA in 12 months (Clinical RR = 1.087 | Radiographic RR = 2.132). The RoB-2 tool showed a low risk of bias in all included RCTs. CONCLUSION: The limited evidence showed the clinical and radiographic efficacy of 3Mixtatin as a potential alternative to MTA. Further empirical research with larger sample sizes and strict methodology will be essential to substantiate this assertion.
Subject(s)
Aluminum Compounds , Calcium Compounds , Drug Combinations , Metronidazole , Oxides , Silicates , Tooth, Deciduous , Humans , Aluminum Compounds/therapeutic use , Calcium Compounds/therapeutic use , Ciprofloxacin/therapeutic use , Evidence-Based Dentistry , Metronidazole/therapeutic use , Minocycline/therapeutic use , Oxides/therapeutic use , Randomized Controlled Trials as Topic , Root Canal Filling Materials/therapeutic use , Silicates/therapeutic useABSTRACT
As an acute ophthalmic infection, bacterial keratitis (BK) can lead to severe visual morbidity, such as corneal perforation, intraocular infection, and permanent corneal opacity, if rapid and effective treatments are not available. In addition to eradicating pathogenic bacteria, protecting corneal tissue from oxidative damage and promoting wound healing by relieving inflammation are equally critical for the efficient treatment of BK. Besides, it is very necessary to improve the bioavailability of drugs by enhancing the ocular surface adhesion and corneal permeability. In this investigation, therefore, a synergistic antibiotic-antioxidant treatment of BK was achieved based on multifunctional block copolymer vesicles, within which ciprofloxacin (CIP) was simultaneously encapsulated during the self-assembly. Due to the phenylboronic acid residues in the corona layer, these vesicles exhibited enhanced muco-adhesion, deep corneal epithelial penetration, and bacteria-targeting, which facilitated the drug delivery to corneal bacterial infection sites. Additionally, the abundant thioether moieties in the hydrophobic membrane enabled the vesicles to both have ROS-scavenging capacity and accelerated CIP release at the inflammatory corneal tissue. In vivo experiments on a mice model demonstrated that the multifunctional polymer vesicles achieved efficient treatment of BK, owing to the enhanced corneal adhesion and penetration, bacteria targeting, ROS-triggered CIP release, and the combined antioxidant-antibiotic therapy. This synergistic strategy holds great potential in the treatment of BK and other diseases associated with bacterial infections.
Subject(s)
Eye Infections, Bacterial , Keratitis , Animals , Mice , Antioxidants/pharmacology , Polymers/chemistry , Reactive Oxygen Species , Keratitis/drug therapy , Keratitis/microbiology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Ciprofloxacin , Eye Infections, Bacterial/drug therapy , Eye Infections, Bacterial/microbiologyABSTRACT
In the scope, developed a novel copper molybdate decorated polymeric graphitic carbon nitride (CuMoO4@g-C3N4 or CMC) heterojunction nanocomposite in an easy solvothermal environment for the first time. The synthesized CMC improved the photocatalytic degradation of an antibiotic drug [ciprofloxacin (CIP)] and organic dye [Rhodamine B (RhB)]. Consequently, the CMC demonstrates a marvelous crystalline nature with â¼26 nm size, as obtained from XRD analysis. Besides, the surface morphology studies confirm the large-scale construction of flower-like CMC with a typical size of 10-15 nm. The CMC showed efficient catalytic activity for both the pollutants, achieving the degradation of 98% for RhB and 97% for CIP in 35 and 60 min, respectively. The reaction parameters including the concentration of pollutants, catalyst dosages, and scavengers are optimized for the best photocatalytic results. Notably, the trapping tests showed that the â¢OH and O2â¢- radicals are the primary oxidative species liable for the photocatalytic process. The recyclability test of the photocatalyst infers that the photocatalyst is highly stable up to the fifth recycle. Our work affords an efficient and ideal path to constructing the new g-C3N4-based architected photocatalyst for toxic wastewater treatment in the near future.
Subject(s)
Copper , Environmental Pollutants , Ciprofloxacin , Polymers , WaterABSTRACT
The accumulation of antibiotics in aquatic environments poses a serious threat to human health. Photocatalytic degradation is a promising method for removing antibiotics from water, but its practical implementation requires improvements in photocatalyst activity and recovery. Here, a novel graphite felt-supported MnS/Polypyrrole composite (MnS/PPy/GF) was constructed to achieve effective adsorption of antibiotics, stable loading of photocatalyst, and rapid separation of spatial charge. Systematic characterization of composition, structure and photoelectric properties indicated the efficient light absorption, charge separation and migration of the MnS/PPy/GF, which achieved 86.2% removal of antibiotic ciprofloxacin (CFX), higher than that of MnS/GF (73.7%) and PPy/GF (34.8%). The charge transfer-generated 1O2, energy transfer-generated 1O2, and photogenerated h+ were identified as the dominant reactive species, which mainly attacked the piperazine ring in the photodegradation of CFX by MnS/PPy/GF. The â¢OH was confirmed to participate in the defluorination of CFX via hydroxylation substitution. The MnS/PPy/GF-based photocatalytic process could ultimately achieve the mineralization of CFX. The facile recyclability, robust stability, and excellent adaptability to actual aquatic environments further confirmed MnS/PPy/GF is a promising eco-friendly photocatalyst for antibiotic pollution control.
Subject(s)
Ciprofloxacin , Graphite , Humans , Ciprofloxacin/chemistry , Graphite/chemistry , Polymers/chemistry , Pyrroles/chemistry , Anti-Bacterial Agents/chemistryABSTRACT
Microplastics (MPs) have recently become an emerging environmental concern. Nevertheless, limited information is known about the adsorption of MPs for organic contaminants under combined heavy metals pollution, with an emphasis on the role of complexation. Thus, this study aims to comprehensively compare and investigate the adsorption performance of antibiotic tetracycline (TC) and ciprofloxacin (CIP) on two polar MPs (polyamide (PA) and polyvinyl chloride (PVC)) affected by Cu(II) and Cd(II) with contrasting complexation abilities. Batch adsorption experiments were used in combination with speciation calculation, zeta potential determination, FTIR spectroscopy characterization and investigation of the affinity of MPs for heavy metals. Results showed that the sorption kinetics and isotherms of TC and CIP on PA and PVC could be well fitted to pseudo-second-order and Langmuir models, respectively, both in the absence and presence of Cu and Cd, suggesting that multiple interactions and monolayer adsorption played an important role in the adsorption process. The presence of Cu substantially improved TC and CIP adsorption and obviously changed the pH dependence of their adsorption onto both MPs, which may result from the Cu-induced strong complexation with TC and CIP. The presence of Cd slightly enhanced TC adsorption on both MPs while reduced CIP adsorption especially on PVC, which may be ascribed to the Cd-induced cationic bridging effects in TC adsorption and the competitive adsorption of Cd in CIP adsorption. Therefore, the heavy metal-mediated complexation effects may play a dominant role in antibiotic adsorption by MPs only in the presence of heavy metals with strong complexation ability while the adsorption performance in the presence of heavy metals with negligible complexation capacity may be influenced by effects other than complexation. This study helps further understand the heavy metal-mediated adsorption behavior of organic contaminants on polar MPs and the role of complexation reactions therein.
Subject(s)
Metals, Heavy , Water Pollutants, Chemical , Microplastics , Adsorption , Ciprofloxacin/chemistry , Plastics , Anti-Bacterial Agents , Cadmium , Polyvinyl Chloride , Metals, Heavy/chemistry , Tetracycline/chemistry , Water Pollutants, Chemical/analysisABSTRACT
Copper oxide nanoparticles (CuO NPs) and ciprofloxacin (CIP) have ecological risk to humans and ecosystems. Polyvinylchloride microplastics (PVC MPs), as a representative of microplastics, may often coexist with CuO NPs and CIP in wastewater treatment systems due to their widespread application. However, the co-impact of PVC MPs in wastewater systems contained with CuO NPs and CIP on nitrogen removal and ecological risk is not clear. In this work, PVC MPs co-impacts on the toxicity of CuO NPs and CIP to aerobic granular sludge (AGS) systems and potential mechanisms were investigated. 10 mg/L PVC MPs co-addition did not significantly affect the nitrogen removal, but it definitely changed the microbial community structure and enhanced the propagation and horizontal transfer of antibiotics resistance genes (ARGs). 100 mg/L PVC MPs co-addition resulted in a raise of CuO NP toxicity to the AGS system, but reduced the co-toxicity of CuO NPs and CIP and ARGs expression. The co-impacts with different PVC MPs concentration influenced Cu2+ concentrations, cell membrane integrity, extracellular polymeric substances (EPS) contents and microbial communities in AGS systems, and lead to a change of nitrogen removal.
Subject(s)
Microbiota , Nanoparticles , Humans , Sewage , Microplastics , Anti-Bacterial Agents , Plastics , Waste Disposal, Fluid , Nitrogen , Denitrification , Nanoparticles/chemistry , Ciprofloxacin , Polyvinyl Chloride , BioreactorsABSTRACT
OBJECTIVE: Chronic bone infection caused by Staphylococcus aureus biofilms in children and adults is characterized by reduced antibiotic sensitivity. In this study, we assessed 'heat-targeted, on-demand' antibiotic delivery for S. aureus killing by combining ciprofloxacin (CIP)-laden low-temperature sensitive liposomes (LTSLs) with local high-intensity focused ultrasound (HIFU) induced bone heating in a rat model of bone infection. METHODS: CIP-LTSLs were prepared using the thin-film hydration and extrusion method. Bone infection was established by surgically implanting an orthopedic K-wire colonized with methicillin-resistant S. aureus (MRSA) strain into rat's femurs. For bone heating, ultrasound-guided HIFU exposures were performed to achieve a local temperature of 40-42 °C (â¼15 min) concurrently with intravenous injection of CIP-LTSLs or CIP. CIP biodistribution was determined spectrophotometrically and therapeutic efficacy was determined by bacteriological, histological and scanning electron microscopy (SEM) analyses. RESULTS: CIP-LTSLs in the range of 183.5 nm ± 1.91 showed an encapsulation efficiency of >70% at 37 °C and a complete release at â¼42 °C. The metal implantation method yielded medullary osteomyelitis characterized by suppurative changes (bacterial and pus pockets) by day 10 in bones and adjoining muscle tissues. HIFU heating significantly improved CIP delivery from LTSLs in bones, resulting in a significant reduction in MRSA load compared to HIFU and CIP alone groups. These were also verified by histology and SEM, wherein a distinct reduction in S. aureus population in the infected metal wires and tissues from the combinatorial therapy was noted. CONCLUSION: HIFU improved CIP delivery to bones, achieving clearance of hard-to-treat MRSA biofilms.
Subject(s)
Methicillin-Resistant Staphylococcus aureus , Osteomyelitis , Animals , Rats , Staphylococcus aureus , Liposomes , Tissue Distribution , Ciprofloxacin , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic useABSTRACT
BACKGROUND: Low-dose antibiotic-loaded acrylic cement is routinely used for preventing skeletal infection or reimplantation in patients with periprosthetic joint infections. However, few reports about the selection of antibiotics in acrylic cement for antigram-negative bacteria have been proposed. QUESTIONS/PURPOSES: (1) Does the addition of antibiotics (tobramycin, meropenem, piperacillin, ceftazidime, ciprofloxacin, and aztreonam) to acrylic cement adversely affect compressive strength before and after elution? (2) Which antibiotics have the highest cumulative release within 28 days? (3) Which antibiotics showed antimicrobial activity within 28 days? (4) Does meropenem-loaded cement improve body weight, temperature, and other inflammatory markers compared with control unloaded cement? METHODS: This is an in vitro study that assessed the mechanical strength, antibiotic elution, and antibacterial properties of antibiotic-loaded cement, combined with an animal study in a rat model that evaluated key endpoints from the animal study. In the in vitro study, we added 2 g of tobramycin (TOB), meropenem (MEM), piperacillin (PIP), ceftazidime (CAZ), ciprofloxacin (CIP), and aztreonam (ATM) to 40 g of acrylic cement. The compressive strength, elution, and in vitro antibacterial properties of the antibiotic-loaded cement were detected. Thirty male rats were randomly divided into two groups: CON (antibiotic-unloaded cement) and MEM (meropenem-loaded cement, which had the most stable antibacterial properties of the six tested antibiotic-loaded cements in vitro within 28 days). The right tibia of all rats underwent arthroplasty and was implanted with the cement, followed by inoculation with Pseudomonas aeruginosa in the knee. General status, serum biomarkers, radiology, microbiological assay, and histopathological tests were assessed over 14 days postoperatively. RESULTS: The compressive strength of all tested antibiotic cement combinations exceeded the 70 MPa threshold (the requirement established in ISO 5833). The cumulative release proportions of the raw antibiotic in cement were 1182.8 ± 37.9 µg (TOB), 355.6 ± 16.2 µg (MEM), 721.2 ± 40.3 µg (PIP), 477.4 ± 37.1 µg (CAZ), 146.5 ± 11.3 µg (CIP), and 372.1 ± 14.5 µg (ATM) within 28 days. Over a 28-day period, meropenem cement demonstrated antimicrobial activities against the four tested gram-negative bacteria ( Escherichia coli , P. aeruginosa , Klebsiella pneumoniae , and Proteus vulgaris ). Ciprofloxacin cement inhibited E. coli growth, ceftazidime and aztreonam cement inhibited K. pneumonia growth, and tobramycin cement inhibited P. aeruginosa . Only meropenem demonstrated antimicrobial activity against all gram-negative bacteria on agar diffusion bioassay. Rats treated with meropenem cement showed improved body weight (control: 280.1 ± 4.2 g, MEM: 288.5 ± 6.6 g, mean difference 8.4 [95% CI 4.3 to 12.6]; p < 0.001), improved knee width (control: 13.5 ± 0.3 mm, MEM: 11.8± 0.4 mm, mean difference 1.7 [95% CI 1.4 to 2.0]; p < 0.001), decreased inflammatory marker (control: 316.7 ± 45.0 mm, MEM: 116.5 ± 21.8 mm, mean difference 200.2 [95% CI 162.3 to 238.2]; p < 0.001), decreased radiographic scores (control: 17.7 ± 2.0 mm, MEM: 10.7± 1.3 mm, mean difference 7.0 [95% CI 5.4 to 8.6]; p < 0.001), improved bone volume/total volume (control: 8.7 ± 3.0 mm, MEM: 28.5 ± 5 .5 mm, mean difference 19.8 [95% CI 13.3 to 26.2]; p < 0.001), decreased Rissing scale scores of the knee gross pathology (control: 3.3 ± 0.5, MEM: 1.1 ± 0.7, mean difference 2.2 [95% CI 1.7 to 2.7]; p < 0.001), decreased Petty scale scores of knee synovium (control: 2.9 ± 0.4 mm, MEM: 0.7 ± 0.7 mm, mean difference 2.1 [95% CI 1.7 to 2.5]; p < 0.001), and decreased bacterial counts of the bone and soft tissues and negative bacterial cultures of cement (p < 0.001, p < 0.001, p < 0.001, p < 0.001, respectively). CONCLUSION: In this current study, MEM cement had the most stable in vitro antimicrobial activities, effective in vivo activity while having acceptable mechanical and elution characteristics, and it may be an effective prophylaxis against skeletal infection caused by gram-negative bacteria. CLINICAL RELEVANCE: Meropenem-loaded acrylic cement is a potentially effective prevention measure for skeletal infection caused by gram-negative bacteria; however, more related clinical research is needed to further evaluate the safety and efficacy.
Subject(s)
Ceftazidime , Osteomyelitis , Male , Animals , Rats , Meropenem/pharmacology , Ceftazidime/pharmacology , Aztreonam/pharmacology , Escherichia coli , Anti-Bacterial Agents/pharmacology , Bone Cements , Tobramycin , Piperacillin , Ciprofloxacin , Models, Animal , Microbial Sensitivity TestsABSTRACT
Ciprofloxacin (CIP), a quinolone antibiotic, was rapidly and sensitively detected by integrating the molecularly imprinted polymer (MIP) with an ultra-sensitive electrochemiluminescence (ECL) method. g-C3N4, a typical polymer semiconductor, exhibited outstanding ECL efficiency and excellent ECL stability after combining with an iron-based metal-organic framework (MIL-101). Subsequently, the molecularly imprinted polypyrrole was electropolymerized on the composites of MIL-101-g-C3N4 modified glassy carbon electrode (GCE). The specific sites that could target rebinding the CIP molecules were formed on the surface of MIP after extracting the CIP templates. The determination of specific concentrations of CIP could be realized according to the difference in ECL intensity (â³ECL) between the eluting and rebinding of the CIP. Under optimal conditions, a good linear response of â³ECL and the logarithm of CIP concentrations was obtained in the range 1.0 × 10-9 ~ 1.0 × 10-5 mol/L, with a detection limit of 4.5 × 10-10 mol/L (S/N = 3) (the working potential was -1.8 ~ 0 V). The RSD of all points in the calibration plot was less than 5.0% and the real samples recovery was between 98.0 and 104%. This paper displays satisfactory selectivity and sensitivity, providing a rapid, convenient, and cheap method for the determination of CIP in real samples.
Subject(s)
Metal-Organic Frameworks , Polymers , Pyrroles , Ciprofloxacin , Molecularly Imprinted PolymersABSTRACT
A novel conductive filament based on graphite (Gr) dispersed in polylactic acid polymer matrix (PLA) is described to produce 3D-electrochemical devices (Gr/PLA). This conductive filament was used to additively manufacture electrochemical sensors using the 3D pen. Thermogravimetric analysis confirmed that Gr was successfully incorporated into PLA, achieving a composite material (40:60% w/w, Gr and PLA, respectively), while Raman and scanning electron microscopy revealed the presence of defects and a high porosity on the electrode surface, which contributes to improved electrochemical performance. The 3D-printed Gr/PLA electrode provided a more favorable charge transfer (335 Ω) than the conventional glassy carbon (1277 Ω) and 3D-printed Proto-pasta® (3750 Ω) electrodes. As a proof of concept, the ciprofloxacin antibiotic, a species of multiple interest, was selected as a model molecule. Thus, a square wave voltammetry (SWV) method was proposed in the potential range + 0.9 to + 1.3 V (vs Ag|AgCl|KCl(sat)), which provided a wide linear working range (2 to 32 µmol L-1), 1.79 µmol L-1 limit of detection (LOD), suitable precision (RSD < 7.9%), and recovery values from 94 to 109% when applied to pharmaceutical and milk samples. Additionally, the sensor is free from the interference of other antibiotics routinely employed in veterinary practices. This device is disposable, cost-effective, feasibly produced in financially limited laboratories, and consequently promising for evaluation of other antibiotic species in routine applications.
Subject(s)
Ciprofloxacin , Graphite , Laboratories , Cost-Benefit Analysis , Electrochemical Techniques/methods , Graphite/chemistry , Anti-Bacterial Agents , Polyesters/chemistry , Printing, Three-DimensionalABSTRACT
This investigation aimed to synthesize poly(D,L-lactide) (PLA)-based fibrous scaffolds containing natural essential oils (i.e., linalool and citral) and determine their antimicrobial properties and cytocompatibility as a clinically viable cell-friendly disinfection strategy for regenerative endodontics. PLA-based fibrous scaffolds were fabricated via electrospinning with different concentrations of linalool and citral. The micromorphology and average diameter of the fibers was investigated through scanning electron microscopy (SEM). The chemical composition of the scaffolds was inferred by Fourier-transform infrared spectroscopy (FTIR). Antimicrobial efficacy against Enterococcus faecalis and Actinomyces naeslundii was also evaluated by agar diffusion and colony-forming units (CFU) assays. The scaffolds' cytocompatibility was determined using dental pulp stem cells (DPSCs). Statistical analyses were performed and the significance level was set at α = 5%. Linalool and citral's incorporation in the PLA fibrous scaffolds was confirmed in the FTIR spectra. SEM images indicate no morphological changes upon inclusion of the essential oils, except the reduced diameter of 40% linalool-laden fibers (p < 0.05). Importantly, significant antimicrobial properties were reported for citral-containing scaffolds for CFU/mL counts (p < 0.05), while only 20% and 40% linalool-laden scaffolds reduced CFU/mL (p < 0.05). Meanwhile, the inhibition halos were verified in a concentration-dependent manner for all monoterpenes-laden scaffolds. Citral- and linalool-laden PLA-based fibrous scaffolds showed acceptable cytocompatibility. The incorporation of natural monoterpenes did not alter the scaffolds' fibrous morphology, promoted antimicrobial action against endodontic pathogens, and preserved DPSCs viability. Linalool- and citral-laden electrospun scaffolds hold promise as naturally derived antimicrobial therapeutics for applications in regenerative endodontics.
Subject(s)
Anti-Infective Agents , Ciprofloxacin , Ciprofloxacin/chemistry , Ciprofloxacin/pharmacology , Monoterpenes/pharmacology , Anti-Infective Agents/pharmacology , Polyesters/pharmacology , Tissue Scaffolds/chemistry , Tissue Engineering/methodsABSTRACT
A new N-doped biochar derived from sugarcane bagasse (NSB) was prepared by one-pot pyrolysis with sugarcane bagasse as feedstock, melamine as nitrogen source and NaHCO3 as pore-forming agent, and then NSB was used to adsorb ciprofloxacin (CIP) in water. The optimal preparation conditions of NSB were determined based on the evaluation index of adsorbability of NSB for CIP. SEM, EDS, XRD, FTIR, XPS and BET characterizations were used to analyze the physicochemical properties of the synthetic NSB. It was found that the prepared NSB had excellent pore structure, high specific surface area and more nitrogenous functional groups. Meanwhile, it was demonstrated that the synergistic interaction between melamine and NaHCO3 increased the pores of NSB and the largest surface area of NSB was 1712.19 m2/g. The CIP adsorption capacity of 212 mg/g was obtained under optimal parameters as follows: NSB amount 0.125 g/L, initial pH 6.58, adsorption temperature 30 °C, CIP initial concentration 30 mg/L and adsorption time 1 h. The isotherm and kinetics studies elucidated that the adsorption of CIP conformed both D-R model and Pseudo-second-order kinetic model. The high CIP adsorption capacity of NSB for CIP was due to the combined filling pore, π-π conjugation and hydrogen bonding. All results demonstrated that adsorption of CIP by the low-cost N-doped biochar of NSB is a reliable technology for the disposal of CIP wastewater.