ORCID Profile
0000-0001-7247-8271
Current Organisations
University of South Australia
,
Flinders University
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Publisher: MDPI AG
Date: 29-12-2022
DOI: 10.3390/NANO13010155
Abstract: Amphotericin B is an antifungal drug used for the treatment of invasive fungal infections. However, its clinical use is limited due to its serious side effects, such as renal and cardiovascular toxicity. Furthermore, hotericin B is administered in high doses due to its poor water solubility. Hence, it is necessary to develop an on-demand release strategy for the delivery of hotericin B to reduce cytotoxicity. The present report describes a novel encapsulation of hotericin B into lipase-sensitive polycaprolactone to form a nanocomposite. Nanocomposites were produced by the oil-in-water method and their physicochemical properties such as size, hydrodynamic diameter, drug loading, and zeta potential were determined. The in vitro release of hotericin B was characterized in the presence and absence of lipase. The antifungal activity of the nanocomposites was verified against lipase-secreting Candida albicans, and cytotoxicity was tested against primary human dermal fibroblasts. In the absence of lipase, the release of hotericin B from the nanocomposites was minimal. However, in the presence of lipase, an enzyme that is abundant at infection sites, a fungicidal concentration of hotericin B was released from the nanocomposites. The antifungal activity of the nanocomposites showed an enhanced effect against the lipase-secreting fungus, Candida albicans, in comparison to the free drug at the same concentration. Furthermore, nanoencapsulation significantly reduced hotericin B-related cytotoxicity compared to the free drug. The synthesized nanocomposites can serve as a potent carrier for the responsive delivery of hotericin B in antifungal applications.
Publisher: Wiley
Date: 03-10-2022
Abstract: An ever‐present risk of medical device associated infection has driven a significant body of research toward development of novel anti‐infective materials. Surfaces bearing sharp nanostructures are an emerging technology to address this concern. The in vitro efficacy of antimicrobial nanostructures has previously been verified using single species cultures, but there remains a paucity of data to address the threat of infections containing more than one species. Polymicrobial infections are a concerning threat because they can complicate treatment, promote drug resistance, and harshen patient prognosis. In the present study, dual‐species cultures are employed to challenge the mechano‐bactericidal properties of nanostructured surfaces. Escherichia coli is used with either Staphylococcus aureus or Enterococcus faecalis due to their clinical relevance in implant associated infection. Despite the presence of two mixed species, a high rate of bactericidal activity is found. Interestingly, in the mixed culture containing Escherichia coli with Enterococcus faecalis , the nanostructured surface triggers a shift in species distribution to favor Enterococcus faecalis . Overall, this study highlights the potential for mechano‐bactericidal surfaces to minimize the burden of infections containing more than one species. It also serves as an enticing foundation for further research into more complex biointerfacial interactions.
Publisher: American Chemical Society (ACS)
Date: 10-08-2021
Abstract: The demand for medical implants globally has increased significantly due to an aging population amongst other reasons. Despite the overall increase in the survivorship of Ti6Al4V implants, implant infection rates are increasing due to factors such as diabetes, obesity, and bacterial resistance to antibiotics. Two commonly found bacteria implicated in implant infections are
Publisher: American Chemical Society (ACS)
Date: 28-07-2023
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 22-08-2012
Publisher: Elsevier BV
Date: 12-2021
Publisher: Wiley
Date: 02-2016
DOI: 10.1111/JCPE.12499
Publisher: Wiley
Date: 04-02-2022
Abstract: There is a globally increasing demand for medically implanted devices, partly spurred by an aging population. In parallel, there is a proportionate increase in implant associated infection. Much focus has been directed toward the development of techniques to fabricate nanostructured antimicrobial biomaterials to mitigate infection. The present study investigates the interaction of the fungal pathogen Candida albicans with an antimicrobial surface bearing nanoscale protrusions. C. albicans cells were observed to be affected by cell wall stress, which impeded its ability to switch to a hyphal phenotype. There are significant differences in the expression of C. albicans virulence‐associated genes between the untreated and nanostructured surfaces. To determine whether the observed inhibition of C. albicans would also sensitize it to antifungal drugs, a culture is established for 3 days on the nanostructured surface before being treated with the antifungal drug hotericin B. The drug was able to kill all cells on the nanostructured surface at sub‐clinical concentrations, while remaining ineffective against cultures grown on a smooth control surface. These findings may eventually prove to be impactful in the clinic, as clinicians may be able to reduce antifungal drug dosages and minimize the effects of drug associated toxicity.
Publisher: Elsevier BV
Date: 09-2022
DOI: 10.1016/J.COLSURFB.2022.112600
Abstract: Medical-grade titanium alloys used for orthopaedic implants are at risk from infections and complications such as wear and tear. We have recently shown that hydrothermally etched (HTE) nanostructures (NS) formed on the Ti6AlV4 alloy surfaces impart enhanced anti-bacterial activity which results in inhibited formation of bacterial biofilm. Although these titanium alloy nanostructures may resist bacterial colonisation, their frictional properties are yet to be understood. Orthopaedic devices are encapsulated by bone and muscle tissue. Contact friction between orthopaedic implant surfaces and these host tissues may trigger inflammation, osteolysis and wear. To address these challenges, we performed simulation of the contact behaviour between a smooth control Ti6Al4V alloy and HTE surfaces against a hardwearing SiO
Publisher: American Chemical Society (ACS)
Date: 29-06-2023
Publisher: MDPI AG
Date: 29-03-2022
DOI: 10.3390/NANO12071140
Abstract: Inspired by observations that the natural topography observed on cicada and dragonfly wings may be lethal to bacteria, researchers have sought to reproduce these nanostructures on biomaterials with the goal of reducing implant-associated infections. Titanium and its alloys are widely employed biomaterials with excellent properties but are susceptible to bacterial colonisation. Hydrothermal etching is a simple, cost-effective procedure which fabricates nanoscale protrusions of various dimensions upon titanium, depending on the etching parameters used. We investigated the role of etching time and the choice of cation (sodium and potassium) in the alkaline heat treatment on the topographical, physical, and bactericidal properties of the resulting modified titanium surfaces. Optimal etching times were 4 h for sodium hydroxide (NaOH) and 5 h for potassium hydroxide (KOH). NaOH etching for 4 h produced dense, but somewhat ordered, surface nanofeatures with 75 nanospikes per µm2. In comparison, KOH etching for 5 h resulted sparser but nonetheless disordered surface morphology with only 8 spikes per µm2. The NaOH surface was more effective at eliminating Gram-negative pathogens, while the KOH surface was more effective against the Gram-positive strains. These findings may guide further research and development of bactericidal titanium surfaces which are optimised for the predominant pathogens associated with the intended application.
Publisher: Oxford University Press (OUP)
Date: 20-09-2013
DOI: 10.1093/BRAIN/AWT249
Abstract: Periventricular nodular heterotopia is caused by defective neuronal migration that results in heterotopic neuronal nodules lining the lateral ventricles. Mutations in filamin A (FLNA) or ADP-ribosylation factor guanine nucleotide-exchange factor 2 (ARFGEF2) cause periventricular nodular heterotopia, but most patients with this malformation do not have a known aetiology. Using comparative genomic hybridization, we identified 12 patients with developmental brain abnormalities, variably combining periventricular nodular heterotopia, corpus callosum dysgenesis, colpocephaly, cerebellar hypoplasia and polymicrogyria, harbouring a common 1.2 Mb minimal critical deletion in 6q27. These anatomic features were mainly associated with epilepsy, ataxia and cognitive impairment. Using whole exome sequencing in 14 patients with isolated periventricular nodular heterotopia but no copy number variants, we identified one patient with periventricular nodular heterotopia, developmental delay and epilepsy and a de novo missense mutation in the chromosome 6 open reading frame 70 (C6orf70) gene, mapping in the minimal critical deleted region. Using immunohistochemistry and western blots, we demonstrated that in human cell lines, C6orf70 shows primarily a cytoplasmic vesicular puncta-like distribution and that the mutation affects its stability and subcellular distribution. We also performed in utero silencing of C6orf70 and of Phf10 and Dll1, the two additional genes mapping in the 6q27 minimal critical deleted region that are expressed in human and rodent brain. Silencing of C6orf70 in the developing rat neocortex produced periventricular nodular heterotopia that was rescued by concomitant expression of wild-type human C6orf70 protein. Silencing of the contiguous Phf10 or Dll1 genes only produced slightly delayed migration but not periventricular nodular heterotopia. The complex brain phenotype observed in the 6q terminal deletion syndrome likely results from the combined haploinsufficiency of contiguous genes mapping to a small 1.2 Mb region. Our data suggest that, of the genes within this minimal critical region, C6orf70 plays a major role in the control of neuronal migration and its haploinsufficiency or mutation causes periventricular nodular heterotopia.
Publisher: Springer Science and Business Media LLC
Date: 18-02-2015
Publisher: American Chemical Society (ACS)
Date: 28-07-2022
DOI: 10.1021/ACS.NANOLETT.2C02182
Abstract: The ever-increasing rate of medical device implantations is met by a proportionately high burden of implant-associated infections. To mitigate this threat, much research has been directed toward the development of antibacterial surface modifications by various means. One recent approach involves surfaces containing sharp nanostructures capable of killing bacteria upon contact. Herein, we report that the mechanical interaction between
Publisher: American Chemical Society (ACS)
Date: 14-10-2022
DOI: 10.1021/ACSBIOMATERIALS.2C00540
Abstract: Titanium and its alloys are frequently the biomaterial of choice for dental implant applications. Although titanium dental implants have been utilized for decades, there are yet unresolved issues pertaining to implant failure. Dental implant failure can arise either through wear and fatigue of the implant itself or peri-implant disease and subsequent host inflammation. In the present report, we provide a comprehensive review of titanium and its alloys in the context of dental implant material, and how surface properties influence the rate of bacterial colonization and peri-implant disease. Details are provided on the various periodontal pathogens implicated in peri-implantitis, their adhesive behavior, and how this relationship is governed by the implant surface properties. Issues of osteointegration and immunomodulation are also discussed in relation to titanium dental implants. Some impediments in the commercial translation for a novel titanium-based dental implant from "bench to bedside" are discussed. Numerous in vitro studies on novel materials, processing techniques, and methodologies performed on dental implants have been highlighted. The present report review that comprehensively compares the in vitro , in vivo , and clinical studies of titanium and its alloys for dental implants.
Publisher: Wiley
Date: 15-09-2023
Publisher: American Chemical Society (ACS)
Date: 27-01-2021
Publisher: Springer Science and Business Media LLC
Date: 13-06-2012
No related grants have been discovered for Andrew Hayles.