ORCID Profile
0000-0003-2979-8215
Current Organisation
Masaryk University
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Publisher: Cold Spring Harbor Laboratory
Date: 25-04-2023
DOI: 10.1101/2023.04.23.537998
Abstract: 1. Few human osteocyte in vitro models exist and the differentiation of immature osteoblasts to an osteocyte stage typically takes at least 4-weeks of culture, making the study of this process challenging and time consuming. The osteosarcoma cell line Saos-2 has proved to be a useful model of human osteoblast differentiation through to a mature osteocyte-like stage. Culture under osteogenic conditions in a standard 5% CO 2 and normoxic (21% O 2 ) atmosphere results in reproducible mineralisation and acquisition of mature osteocyte markers over the expected 28-35 day culture period. In order to expedite experimental assays, we tested whether reducing available oxygen to mimic concentrations experienced by osteocytes in vivo would increase the rate of differentiation of Saos-2 cells. Cells cultured in a 5% CO 2 , 1% O 2 atmosphere exhibited accelerated deposition of mineral, reaching near saturation by 14 days as demonstrated with the Alizarin Red and Von Kossa staining. The gene expression of the major hypoxia-induced transcription factor HIF1α and the key osteogenic transcription factor RUNX2 were both elevated under 1% O 2 . Early ( COLA1, MEPE ) and mature ( PHEX, DMP1 and SOST ) osteocyte markers were also upregulated earlier under hypoxic compared to normoxic growth conditions. Thus, culture under low oxygen accelerates key markers of osteocyte differentiation, resulting in a useful human osteocyte-like in vitro cell model within 14 days.
Publisher: Springer International Publishing
Date: 2022
Publisher: Wiley
Date: 25-02-2016
DOI: 10.1002/ALR.21735
Abstract: Biofilms are clusters of bacteria embedded in a protective matrix that frequently cause failure of medical treatments and increase the risk of recurrent infections. In particular, Staphylococcus aureus biofilms are associated with a series of chronic and nosocomial infections that are increasingly resistant to antibiotics. This study proposes a novel intervention strategy targeting the essential iron metabolism for bacterial growth, survival and pathogenesis using the compounds deferiprone (Def) and gallium-protoporphyrin (GaPP). S. aureus biofilms were challenged with Def/GaPP as single and dual treatments. In vitro anti-biofilm efficacy was assessed by the AlamarBlue viability assay and confocal microscopy. In vitro cytotoxicity of the treatments was examined by the lactate dehydrogenase assay on mouse fibroblast (L929) and human bronchial epithelial cells (Nuli-1). Def (20 mM) and GaPP (200 μg/mL) monotherapy for 2 hours showed 35% and 74% biofilm removal, respectively, whereas simultaneous Def/GaPP administration showed 55% biofilm removal. In contrast, the consecutive treatment (2 hours Def followed by 2 hours GaPP) achieved 95% biofilm removal. Cytotoxicity studies indicated no cell hazard in all treatments. This study demonstrated the in vitro efficacy of a novel treatment combination against S. aureus biofilms targeting the bacterial iron metabolism. The consecutive Def/GaPP treatment showed significantly enhanced biofilm efficacy than the in idual compounds, while being not toxic to 2 cell lines. This novel treatment combination is a promising approach to combat S. aureus-associated biofilm infections having high potential for future clinical application.
Publisher: Springer Science and Business Media LLC
Date: 12-08-2022
DOI: 10.1038/S41413-022-00227-8
Abstract: Approximately 40% of treatments of chronic and recurrent osteomyelitis fail in part due to bacterial persistence. Staphylococcus aureus , the predominant pathogen in human osteomyelitis, is known to persist by phenotypic adaptation as small-colony variants (SCVs) and by formation of intracellular reservoirs, including those in major bone cell types, reducing susceptibility to antibiotics. Intracellular infections with S. aureus are difficult to treat however, there are no evidence-based clinical guidelines addressing these infections in osteomyelitis. We conducted a systematic review of the literature to determine the demonstrated efficacy of all antibiotics against intracellular S. aureus relevant to osteomyelitis, including protein biosynthesis inhibitors (lincosamides, streptogramins, macrolides, oxazolidines, tetracyclines, fusidic acid, and aminoglycosides), enzyme inhibitors (fluoroquinolones and ansamycines), and cell wall inhibitors (beta-lactam inhibitors, glycopeptides, fosfomycin, and lipopeptides). The PubMed and Embase databases were screened for articles related to intracellular S. aureus infections that compared the effectiveness of multiple antibiotics or a single antibiotic together with another treatment, which resulted in 34 full-text articles fitting the inclusion criteria. The combined findings of these studies were largely inconclusive, most likely due to the plethora of methodologies utilized. Therefore, the reported findings in the context of the models employed and possible solutions for improved understanding are explored here. While rif icin, oritavancin, linezolid, moxifloxacin and oxacillin were identified as the most effective potential intracellular treatments, the scientific evidence for these is still relatively weak. We advocate for more standardized research on determining the intracellular effectiveness of antibiotics in S. aureus osteomyelitis to improve treatments and patient outcomes.
Publisher: Springer Science and Business Media LLC
Date: 31-10-2019
DOI: 10.1007/S10029-019-02063-Y
Abstract: The purpose of this paper is to communicate two new concepts with the potential to cause major morbidity in hernia repair, effective porosity and biofilm. These 2 concepts are interrelated and have the potential to result in mesh-related complications. Effective porosity is a term well described in the textile industry. It is best defined as the changes to pore morphology after implantation of mesh in situ. It is heavily dependent on mesh construct and repair technique and has the potential to impact hernia repair by reducing mesh tissue integration and promoting fibrosis. Bacterial biofilm is a well-described condition affecting prosthesis in breast and join replacement surgery with catastrophic consequences. There is a paucity of information on bacterial biofilm in mesh hernia repair. We speculate that bacterial biofilm has the potential to reduce the effective porosity of mesh, resulting in non-suppurative mesh-related complications as well as the potential for late suppurative infections. We describe the aetiology, pathogenesis, diagnosis, treatment and preventative measures to address bacterial biofilm in mesh hernia surgery. Hernia surgeons should be familiar with these two new concepts which have the potential to cause major morbidity in hernia repair and know how to address them. Ovid Medline and PubMed were searched for communications on "effective porosity" and "bacterial biofilm". There is a paucity of information in the literature of these conditions and their impact on outcomes following mesh hernia repair. We discuss the two concepts of effective porosity and biofilm and propose potential measures to reduce mesh-related complications. This includes choosing mesh with superior mesh construct and technical nuances in implanting mesh to improve effective porosity. Furthermore, measures to reduce bacterial biofilm and its consequences are suggested.
Publisher: Springer Science and Business Media LLC
Date: 14-03-2022
DOI: 10.1007/S10029-022-02583-0
Abstract: The purpose of this study was to investigate the link between bacterial biofilms and negative outcomes of hernia repair surgery. As biofilms are known to play a role in mesh-related infections, we investigated the presence of biofilms on hernia meshes, which had to be explanted due to mesh failure without showing signs of bacterial infection. In this retrospective observational study, 20 paraffin-embedded tissue sections from explanted groin hernia meshes were analysed. Meshes have been removed due to chronic pain, hernia recurrence or mesh shrinkage. The presence and bacterial composition of biofilms were determined. First, specimens were stained with fluorescence in situ hybridisation (FISH) probes, specific for Staphylococcus aureus and coagulase-negative staphylococci, and visualised by confocal laser scanning microscopy. Second, DNA was extracted from tissue and identified by S. aureus and S. epidermidis specific PCR. Confocal microscopy showed evidence of bacterial biofilms on meshes in 15/20 (75.0%) s les, of which 3 were positive for S. aureus , 3 for coagulase-negative staphylococci and 9 for both species. PCR analysis identified biofilms in 17/20 (85.0%) s les, of which 4 were positive for S. aureus , 4 for S. epidermidis and 9 for both species. Combined results from FISH/microscopy and PCR identified staphylococci biofilms in 19/20 (95.0%) mesh s les. Only 1 (5.0%) mesh s le was negative for bacterial biofilm by both techniques. Results suggest that staphylococci biofilms may be associated with hernia repair failure. A silent, undetected biofilm infection could contribute to mesh complications, chronic pain and exacerbation of disease.
Publisher: Royal Society of Chemistry (RSC)
Date: 2015
DOI: 10.1039/C4TB01953A
Abstract: The anti-biofilm effect of drug delivery systems composed of the antiseptic quaternary ammonium compound cetylpyridinium chloride (CPC) and cholesterol was evaluated in Staphylococcus aureus biofilm.
Publisher: Elsevier BV
Date: 02-2020
DOI: 10.1016/J.JOCN.2019.12.042
Abstract: Spinal laminectomy is a common procedure performed to relieve neural compression in patients suffering from myelopathy or radiculopathy. However, up to 40% of patients suffer from persistent post-operative pain and disability, a condition known as Failed Back Surgery Syndrome (FBSS). Excessive scarring in the surgical bed is implicated as a cause. Hydrogels have been proposed to prevent adhesion formation post-laminectomy however, their efficacy has not been proven. This study uses Chitogel complexed with the iron chelator Deferiprone (Def) to prevent adhesion formation in a sheep laminectomy model. Fifteen Adult Merino sheep (Ovis Aries, 1-5 yrs old) underwent laminectomy at lumbar levels 1-5 and had hydrated aluminum silicate (kaolin) applied to promote adhesion formation. Subjects were randomised to receive at each laminectomy level no-treatment control, Chitogel, Chitogel with Def at 20 mM or 40 mM or Carboxy-methyl-cellulose and Polyethylene oxide (CMC/PEO) gel. The animals were recovered for 3 months post-surgery, followed by assessment with Magnetic Resonance Imaging (MRI) and histopathology of the spinal tissues for evaluating the presence and extent of adhesions. MRI and Histology assessment indicated that Kaolin induced severe inflammation with adhesion formation. Chitogel with and without 20 mM Def decreased inflammation (p < 0.01) and trended to reduce adhesions (p < 0.1). Chitogel with Def 40 mM was not significantly dis-similar to CMC/PEO and did not reduce inflammation or adhesions compared to no-treatment control. Chitogel in combination with Def 20 mM is safe and effective in decreasing the inflammatory process and may possibly reduce post-operative adhesions following laminectomy.
Publisher: Springer International Publishing
Date: 2022
Publisher: Frontiers Media SA
Date: 02-08-2017
Publisher: American Society for Microbiology
Date: 06-2017
DOI: 10.1128/AAC.00481-17
Abstract: Many infectious diseases are associated with multidrug-resistant (MDR) bacteria residing in biofilms that require high antibiotic concentrations. While oral drug delivery is frequently ineffective, topical treatments have the potential to deliver higher drug concentrations to the infection site while reducing systemic side effects. This study determined the antibiofilm activity of a surgical wound gel loaded with the iron chelator deferiprone (Def) and the heme analogue gallium-protoporphyrin (GaPP), alone and in combination with ciprofloxacin. Activity against MDR Staphylococcus aureus , Staphylococcus epidermidis , Pseudomonas aeruginosa , and Acinetobacter johnsonii biofilms was assessed in the colony biofilm and artificial wound model by enumeration of CFU and correlative light/electron microscopy. While Staphylococcus biofilms were equally susceptible to GaPP and Def-GaPP gels (log 10 reduction of 3.8 and 3.7, respectively), the Def-GaPP combination was crucial for significant activity against P. aeruginosa biofilms (log 10 reduction of 1.3 for GaPP and 3.3 for Def-GaPP). When Def-GaPP gel was combined with ciprofloxacin, the efficacy exceeded the activity of the in idual compounds. Def-GaPP delivered in a surgical wound gel showed significant antibiofilm activity against different MDR strains and could enhance the gel's wound-healing properties. Moreover, Def-GaPP indicated a potentiation of ciprofloxacin. This antibiofilm strategy has potential for clinical utilization as a therapy for topical biofilm-related infections.
Publisher: Elsevier BV
Date: 12-2014
Publisher: MDPI AG
Date: 18-12-2022
DOI: 10.3390/PHARMACEUTICS14122841
Abstract: Prophylaxis and the treatment of surgical site infections (SSIs) with antibiotics frequently fail due to the antibiotic resistance of bacteria and the ability of bacteria to reside in biofilms (i.e., bacterial clusters in a protective matrix). Therefore, alternative antibacterial treatments are required to combat biofilm infections. The combination of diethyldithiocarbamate (DDC−) and copper ions (Cu2+) exhibited antibiofilm activity against the staphylococci species associated with SSIs however, the formation of a water-insoluble Cu(DDC)2 complex limits its application to SSIs. Here, we describe the development and antibiofilm activity of an injectable gel containing a liposomal formulation of Cu(DDC)2 and Cu2+ (lipogel). Lyophilized liposomes were incorporated into a mixture of chitosan (CS) and beta-glycerophosphate (βGP), and the thermosensitive gelling properties of CS-βGP and the lipogel were determined. The liposomes remained stable after lyophilization over six months at 4–6 °C and −20 °C. The sol-gel transition of the gel and lipogel occurred between 33 and 39 °C, independently of sterilization or storage at −20 °C. CS-βGP is biocompatible and the liposomes were released over time. The lipogel prevented biofilm formation over 2 days and killed 98.7% of the methicillin-resistant Staphylococcus aureus and 99.9% of the Staphylococcus epidermidis biofilms. Therefore, the lipogel is a promising new prophylaxis and treatment strategy for local application to SSIs.
Publisher: Frontiers Media SA
Date: 22-06-2017
Publisher: Wiley
Date: 14-12-2017
DOI: 10.1002/ALR.22046
Abstract: Bacteriophage (phage) therapy has been proposed as an alternative to antibiotics. Phages have been shown to kill antibiotic resistant Staphylococcus aureus strains however, it is unknown whether stress-induced antibiotic tolerance affects S. aureus susceptibility to phages. Our objective was to determine the effectiveness of 2 phages currently in clinical development, against antibiotic-resistant and induced antibiotic-tolerant clinical S. aureus isolates. Antibiotic tolerant S. aureus strains were induced by incubation with increasing concentrations of gentamicin, mupirocin, and ciprofloxacin over time and their susceptibility to 2 clinically relevant phages (Sa83 and Sa87) was assessed. In addition, phage susceptibility was tested in relation to the antibiotic sensitivity of 65 clinical S. aureus isolates, harvested from the sinonasal cavities of chronic rhinosinusitis (CRS) patients. Phage sensitivity was assessed using a plaque spot assay and by measuring optical density values to observe planktonic S. aureus growth in the presence of the phage. Alamar Blue assays were used to assess biofilm viability after phage treatment. Frequency of antibiotic resistance amongst clinical S. aureus isolates was 90.7% (59/65) with 13 of 65 (20.0%) identified as multidrug-resistant. Tolerance to gentamicin, mupirocin, and ciprofloxacin was rapidly induced by incubation with increasing concentrations of respective antibiotics. There was no significant difference in phage sensitivity between antibiotic-sensitive and resistant/tolerant S. aureus clinical isolates in planktonic and biofilm form. Clinical S. aureus isolates from CRS patients have a high (20%) incidence of multidrug resistance. Antibiotic resistance or tolerance did not affect phage susceptibility of those isolates.
Publisher: Portland Press Ltd.
Date: 28-02-2017
DOI: 10.1042/EBC20160056
Abstract: Many bacterial infections in humans and animals are caused by bacteria residing in biofilms, complex communities of attached organisms embedded in an extracellular matrix. One of the key properties of microorganisms residing in a biofilm is decreased susceptibility towards antimicrobial agents. This decreased susceptibility, together with conventional mechanisms leading to antimicrobial resistance, makes biofilm-related infections increasingly difficult to treat and alternative antibiofilm strategies are urgently required. In this review, we present three such strategies to combat biofilm-related infections with the important human pathogen Staphylococcus aureus: (i) targeting the bacterial communication system with quorum sensing (QS) inhibitors, (ii) a ‘Trojan Horse’ strategy to disturb iron metabolism by using gallium-based therapeutics and (iii) the use of ‘non-antibiotics’ with antibiofilm activity identified through screening of repurposing libraries.
Publisher: MDPI AG
Date: 27-08-2023
DOI: 10.3390/ANTIBIOTICS12091371
Abstract: Plasma-treated water (PTW) has emerged as a potential sanitizing agent. This study evaluated antibacterial activity, inhibition of invasion, and biofilm disruption effects of PTW against Salmonella Typhimurium. Minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) were determined for different PTW types. Time-kill assays were conducted to assess bactericidal effects, while polarized Caco-2 cells were used to evaluate invasion inhibition. Biofilm formation and cell viability were examined following PTW treatment using Salmonella Typhimurium isolates, while biofilm disruption and regrowth prevention were investigated using the Bioflux system. PTW exhibited antibacterial activity against all Salmonella Typhimurium isolates, with MICs of 25% for PTW1 and PTW2, and 50% for PTW3, PTW4, and PTW5. MBCs of 50% in media were observed for all PTW types. Undiluted PTW1 and PTW2 showed the highest bactericidal capacity, significantly reduced Salmonella viability, and completely inhibited bacterial invasion, while PTW3 and PTW5 also showed significant invasion reduction. Bioflux experiments confirmed the eradication of biofilms by PTW1 and PTW2, with no regrowth observed 72 h after PTW was removed. PTW demonstrated significant antibacterial activity, inhibition of invasion, biofilm disruption, and reduction of bacterial viability against Salmonella Typhimurium. This highlights PTW’s potential as an effective sanitizer for reducing Salmonella contaminations.
Publisher: Cambridge University Press (CUP)
Date: 07-08-2019
DOI: 10.1017/RDC.2019.85
Abstract: New radiocarbon ( 14 C) dates suggest a simultaneous appearance of two technologically and geographically distinct axe production practices in Neolithic Britain igneous open-air quarries in Great Langdale, Cumbria, and from flint mines in southern England at ~4000–3700 cal BC. In light of the recent evidence that farming was introduced at this time by large-scale immigration from northwest Europe, and that expansion within Britain was extremely rapid, we argue that this synchronicity supports this speed of colonization and reflects a knowledge of complex extraction processes and associated exchange networks already possessed by the immigrant groups long-range connections developed as colonization rapidly expanded. Although we can model the start of these new extraction activities, it remains difficult to estimate how long significant production activity lasted at these key sites given the nature of the record from which s les could be obtained.
Publisher: American Chemical Society (ACS)
Date: 23-06-2017
Abstract: Biofilms are aggregates of bacteria residing in a self-assembled matrix, which protects these sessile cells against external stress, including antibiotic therapies. In light of emerging multidrug-resistant bacteria, alternative strategies to antibiotics are emerging. The present study evaluated the activity of colloidal silver nanoparticles (AgNPs) of different shapes against biofilms formed by Staphylococcus aureus (SA), methicillin-resistant SA (MRSA), and Pseudomonas aeruginosa (PA). Colloidal quasi-spherical, cubic, and star-shaped AgNPs were synthesized, and their cytotoxicity on macrophages (THP-1) and bronchial epithelial cells (Nuli-1) was analyzed by the lactate dehydrogenase assay. The antibiofilm activity was assessed in vitro by the resazurin assay and in an in vivo infection model in Caenorhabditis elegans. Cubic and star-shaped AgNPs induced cytotoxicity, while quasi-spherical AgNPs were not toxic. Quasi-spherical AgNPs showed substantial antibiofilm activity in vitro with 96% (±2%), 97% (±1%), and 98% (±1%) biofilm killing of SA, MRSA, and PA, respectively, while significantly reducing mortality of infected nematodes. The in vivo antibiofilm activity was linked to the accumulation of AgNPs in the intestinal tract of C. elegans as observed by 3D X-ray tomography. Quasi-spherical AgNPs were physically stable in suspension for over 6 months with no observed loss in antibiofilm activity. While toxicity and stability limited the utilization of cubic and star-shaped AgNPs, quasi-spherical AgNPs could be rapidly synthesized, were stable and nontoxic, and showed substantial in vitro and in vivo activity against clinically relevant biofilms. Quasi-spherical AgNPs hold potential as pharmacotherapy, for ex le, as topical treatment for biofilm-related infections.
Publisher: CSIRO Publishing
Date: 2019
DOI: 10.1071/MA19049
Publisher: Elsevier BV
Date: 12-2020
Publisher: Springer International Publishing
Date: 2022
Publisher: Springer Science and Business Media LLC
Date: 09-02-2018
DOI: 10.1038/S41598-018-21141-2
Abstract: Staphylococcus aureus is a major cause of nosocomial infections and secretes a erse spectrum of virulence determinants as well as forms biofilm. The emergence of antibiotic-resistant S . aureus highlights the need for alternative forms of therapeutics other than conventional antibiotics. One route to meet this need is screening small molecule derivatives for potential anti-infective activity. Using a previously optimized C . elegans – S . aureus small molecule screen, we identified a benzimidazole derivative, UM-C162, which rescued nematodes from a S . aureus infection. UM-C162 prevented the formation of biofilm in a dose-dependent manner without interfering with bacterial viability. To examine the effect of UM-C162 on the expression of S . aureus virulence genes, a genome-wide transcriptome analysis was performed on UM-C162-treated pathogen. Our data indicated that the genes associated with biofilm formation, particularly those involved in bacterial attachment, were suppressed in UM-C162-treated bacteria. Additionally, a set of genes encoding vital S . aureus virulence factors were also down-regulated in the presence of UM-C162. Further biochemical analysis validated that UM-C162-mediated disruption of S . aureus hemolysins, proteases and clumping factors production. Collectively, our findings propose that UM-C162 is a promising compound that can be further developed as an anti-virulence agent to control S . aureus infections.
Publisher: American Society for Microbiology
Date: 03-2018
Abstract: “Pint of Science” is an outreach activity bringing the latest scientific discoveries to the community in the relaxed atmosphere of a pub. Founded in the United Kingdom in 2012, this three-night festival in May is now held annually in cities around the world. Today, Pint of Science contributes to science education and engages peers and the public alike, demystifying science at a pub near you. This article gives advice about how to organize a Pint of Science festival, as exemplified by the Adelaide/South Australia chapter’s 2017 experience.
Publisher: Elsevier BV
Date: 09-2021
Publisher: Frontiers Media SA
Date: 09-09-2022
DOI: 10.3389/FMICB.2022.999893
Abstract: Staphylococcus aureus and Staphylococcus epidermidis are associated with life-threatening infections. Despite the best medical care, these infections frequently occur due to antibiotic resistance and the formation of biofilms of these two bacteria (i.e., clusters of bacteria embedded in a matrix). As a consequence, there is an urgent need for effective anti-biofilm treatments. Here, we describe the antibacterial properties of a combination treatment of diethyldithiocarbamate (DDC) and copper ions (Cu 2+ ) and their low toxicity in vitro and in vivo . The antibacterial activity of DDC and Cu 2+ was assessed in vitro against both planktonic and biofilm cultures of S. aureus and S. epidermidis using viability assays, microscopy, and attachment assays. Cytotoxicity of DDC and Cu 2+ (DDC-Cu 2+ ) was determined using a human fibroblast cell line. In vivo antimicrobial activity and toxicity were monitored in Galleria mellonella larvae. DDC-Cu 2+ concentrations of 8 μg/ml DDC and 32 μg/ml Cu 2+ resulted in over 80% MRSA and S. epidermidis biofilm killing, showed synergistic and additive effects in both planktonic and biofilm cultures of S. aureus and S. epidermidis , and synergized multiple antibiotics. DDC-Cu 2+ inhibited MRSA and S. epidermidis attachment and biofilm formation in the xCELLigence and Bioflux systems. In vitro and in vivo toxicity of DDC, Cu 2+ and DDC-Cu 2+ resulted in & 70% fibroblast viability and & 90% G. mellonella survival. Treatment with DDC-Cu 2+ significantly increased the survival of infected larvae (87% survival of infected, treated larvae vs . 47% survival of infected, untreated larvae, p & 0.001). Therefore, DDC-Cu 2+ is a promising new antimicrobial with activity against planktonic and biofilm cultures of S. epidermidis and S. aureus and low cytotoxicity in vitro . This gives us high confidence to progress to mammalian animal studies, testing the antimicrobial efficacy and safety of DDC-Cu 2+ .
Publisher: Elsevier BV
Date: 12-2023
Publisher: Springer International Publishing
Date: 2022
Publisher: Springer Science and Business Media LLC
Date: 02-04-2014
Publisher: Frontiers Media SA
Date: 11-05-2018
Publisher: Elsevier BV
Date: 10-2016
DOI: 10.1016/J.XPHS.2016.06.022
Abstract: Bacterial biofilms are associated with a number of recurring infectious diseases and are a major cause for antibiotic resistance. Despite the broad use of polymeric microparticles and nanoparticles in biomedical research, it is not clear which particle size is more effective against biofilms. The purpose of this study was to evaluate the efficacy of sustained release poly-lactic-co-glycolic acid (PLGA) micro- and nanoparticles containing ciprofloxacin against biofilms of Staphylococcus aureus and Pseudomonas aeruginosa. The PLGA particles were prepared by the double emulsion solvent evaporation method. The resulting microparticles (12 μm) and nanoparticles (300 nm) contained drug loads of 7.3% and 4.5% (wt/wt) ciprofloxacin, respectively. Drug release was complete within 1 week following comparable release profiles for both particle sizes. Micro- and nanoparticles demonstrated a similar in vitro antibiofilm performance against mature P aeruginosa and S aureus with marked differences between the 2 strains. The sustained release of ciprofloxacin from micro- and nanoparticles over 6 days was equally effective as the continuous treatment with ciprofloxacin solution over the same period resulting in the eradication of culturable S aureus suggesting that reformulation of ciprofloxacin as sustained release PLGA micro- and nanoparticles might be valuable formulation approaches for the treatment of biofilms.
Publisher: American Chemical Society (ACS)
Date: 12-11-2015
DOI: 10.1021/ACS.MOLPHARMACEUT.5B00622
Abstract: A Pluronic-functionalized silica-lipid hybrid (Plu-SLH) microparticle system for the oral delivery of poorly water-soluble, weak base drugs is reported for the first time. A highly effective Plu-SLH microparticle system was composed of Labrasol as the lipid phase, Pluronic F127 as the polymeric precipitation inhibitor (PPI), and silica nanoparticles as the solid carrier. For the model drug cinnarizine (CIN), the Plu-SLH delivery system was shown to offer significant biopharmaceutical advantages in comparison with unformulated drug and drug in the silica-lipid hybrid (SLH) system. In vitro two-phase dissolution studies illustrated significantly reduced pH provoked CIN precipitation and an 8- to 14-fold improvement in the extent of dissolution in intestinal conditions. In addition, under simulated intestinal digesting conditions, the Plu-SLH provided approximately three times more drug solubilization than the SLH. Oral administration in rats resulted in superior bioavailability for Plu-SLH microparticles, i.e., 1.6- and 2.1-fold greater than the SLH and the unformulated CIN, respectively. A physical mixture of Pluronic and SLH (Plu&SLH), having the same composition as Plu-SLH, was also evaluated, but showed no significant increase in CIN absorption when compared to unmodified CIN or SLH. This work represents the first study where different methods of incorporating PPI to formulate solid-state lipid-based formulations were compared for the impact on the biopharmaceutical performance. The data suggest that the novel physicochemical properties and structure of the fabricated Plu-SLH microparticle delivery system play an important role in facilitating the synergistic advantage of Labrasol and Pluronic F127 in preventing drug precipitation, and the Plu-SLH provides efficient oral delivery of poorly water-soluble weak bases.
Publisher: Wiley
Date: 12-02-2019
DOI: 10.1002/ALR.22312
Abstract: Topical budesonide (Pulmicort AstraZeneca AB, Sodertalje, Sweden) is commonly used in the management of chronic rhinosinusitis (CRS). Although its use is due to its perceived anti-inflammatory effect, studies have suggested that it may also have antibacterial properties. To make the hydrophobic steroid molecule suitable for topical administration, pharmaceutical excipients are used in commercial steroid formulations. Herein we investigated the antibacterial action of commercial budesonide and its excipients. Planktonic and biofilm forms of Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) were treated with Pulmicort or its excipients at clinically relevant concentrations. Bacterial growth was determined by optical density, resazurin assays, colony-forming unit counts, and Giemsa staining. Minimum inhibitory concentration (MIC) studies assessed excipients' potentiation of antibiotics. Experiments were conducted in triplicate and results analyzed using one-way analysis of variance. There was significant reduction in planktonic and biofilm growth of S aureus and MRSA on exposure to budesonide (p < 0.0001) and its excipients (p < 0.0001). Excipient ethylene diamine-tetraactic acid (EDTA) demonstrated an antibacterial property even at the low concentrations used in topical preparations (p < 0.0001). With amoxicillin, excipients exhibited a potential additive/synergistic effect on MIC, whereas erythromycin and aminoglycosides showed an antagonistic action. The commercial product Pulmicort has a direct antibacterial effect on the planktonic and biofilm forms of S aureus and MRSA. This effect is at least in part mediated through the excipient EDTA in the product. Excipients also influenced the antimicrobial activity of antibiotics depending on the bacterial strain and antibiotic tested.
Publisher: Elsevier BV
Date: 02-2021
Publisher: MDPI AG
Date: 25-02-2023
DOI: 10.3390/SU15054174
Abstract: New Engineering Education (NEE) has become increasingly important in higher education in China. The COVID-19 pandemic has forced higher education institutions to adopt online and hybrid modes of instruction globally, with Massive Open Online Courses (MOOCs) becoming a primary educational tool. In this paper, we explore the impacts of online/hybrid modes on NEE courses in the context of the COVID-19 pandemic. We hypothesized that the rapid transition to online/hybrid modes may have negatively affected students due to insufficient preparation by teachers. This hypothesis was tested through an investigation involving 787 students conducted in 2020 and 2021. The results indicated that, while most students considered online/hybrid modes a helpful tool for their studies, 28.69–36.74% of participants reported significant issues. Through one-to-one interviews with negative/neutral attitude students, we found that insufficient and burdensome communication/interaction with classmates and teachers was the main contributor to these issues. We conclude by proposing a conceptual path to address the issues raised in the study, as well as offering the obtained results as a critical reference for educational researchers seeking to improve the quality of online/hybrid courses and contribute to the field of education.
Location: New Zealand
Location: Denmark
Start Date: 2019
End Date: End date not available
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2019
End Date: End date not available
Funder: National Health and Medical Research Council
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