Browsing by Author "Mansour, Omar T."

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    The antimicrobial effects of the alginate oligomer OligoG CF-5/20 are independent of direct bacterial cell membrane disruption
    (Springer Nature, 2017-03-31) Pritchard, Manon F.; Powell, Lydia C.; Khan, Saira; Griffiths, Peter C.; Mansour, Omar T.; Schweins, Ralf; Beck, Konrad; Buurma, Niklaas J.; Dempsey, Christopher E; Wright, Chris J; Rye, Philip D; Hill, Katja E.; Thomas, David W.; Ferguson, Elaine L.
    Concerns about acquisition of antibiotic resistance have led to increasing demand for new antimicrobial therapies. OligoG CF-5/20 is an alginate oligosaccharide previously shown to have antimicrobial and antibiotic potentiating activity. We investigated the structural modification of the bacterial cell wall by OligoG CF-5/20 and its effect on membrane permeability. Binding of OligoG CF-5/20 to the bacterial cell surface was demonstrated in Gram-negative bacteria. Permeability assays revealed that OligoG CF-5/20 had virtually no membrane-perturbing effects. Lipopolysaccharide (LPS) surface charge and aggregation were unaltered in the presence of OligoG CF-5/20. Small angle neutron scattering and circular dichroism spectroscopy showed no substantial change to the structure of LPS in the presence of OligoG CF-5/20, however, isothermal titration calorimetry demonstrated a weak calcium-mediated interaction. Metabolomic analysis confirmed no change in cellular metabolic response to a range of osmolytes when treated with OligoG CF-5/20. This data shows that, although weak interactions occur between LPS and OligoG CF-5/20 in the presence of calcium, the antimicrobial effects of OligoG CF-5/20 are not related to the induction of structural alterations in the LPS or cell permeability. These results suggest a novel mechanism of action that may avoid the common route in acquisition of resistance via LPS structural modification.
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    Assembly of small molecule surfactants at highly dynamic air-water interfaces
    (Royal Society of Chemistry, 2017-11-10) Mansour, Omar T.; Cattoz, Beatrice; Beaube, Manon; Montagnon, Morganne; Heenan, Richard K.; Schweins, Ralf; Appavou, Marie-Sousai; Griffiths, Peter C.
    Small-angle neutron scattering has been used to probe the interfacial structure of foams stabilised by small molecule surfactants at concentrations well below their critical micelle concentration. The data for wet foams showed a pronounced Q−4 dependence at low Q and noticeable inflexions over the mid Q range. These features were found to be dependent on the surfactant structure (mainly the alkyl chain length) with various inflexions across the measured Q range as a function of the chain length but independent of factors such as concentration and foam age/height. By contrast, foam stability (for C < CMC) was significantly different at this experimental range. Drained foams showed different yet equally characteristic features, including additional peaks attributed to the formation of classical micellar structures. Together, these features suggest the dynamic air–water interface is not as simple as often depicted, indeed the data have been successfully described by a model consisting paracrystalline stacks (multilayer) of adsorbed surfactant layers; a structure that we believe is induced by the dynamic nature of the air–water interface in a foam.
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    The characterisation of Pluronic P123 micelles in the presence of sunscreen agents
    (Wiley, 2023-03-31) Ragu, Pauline; Ruparelia, Ketan; Alba-Venero, Diego; Mansour, Omar T.
    OBJECTIVES The triblock copolymer Pluronic® is widely used in the personal care industry, including sun protection, for its film forming and solubilisation capabilities. In this study, the effect of three commonly used organic UV filters (ethylhexyl methoxycinnamate (EMC), ethylhexyl triazone (EHT) and avobenzone (AVB)) on the structure of Pluronic P123 micelles was investigated. METHODS The Pluronic P123 micelle structure has been investigated using dynamic surface tension, nuclear magnetic resonance (NMR) and small-angle neutron scattering (SANS). RESULTS Dynamic surface tension results show strong interactions between the UV filters and Pluronic® evident by sharp changes in the surface activity of the latter. The NMR results have revealed the creation of a hydrophobic microenvironment special to the Pluronic PPO core group in the presence of UV filters. Some interaction with the hydrophilic EO was also recorded, albeit weaker. This is further confirmed by SANS, where the Pluronic P123 micelles interacted with varying strengths with the UV filters, resulting in sharp changes in their size and shape. CONCLUSIONS We have demonstrated the sensitivity of the Pluronic P123 micelles to the presence of various UVA/B filters. The micelles shape varied from spherical to cylindrical as the concentration and type of the UV filters were varied. These variations in the shape are expected to have a significant effect on the sun protection factor (SPF), as it affects the solubilisation of the UV filters within a formulation in addition to the formulations’ rheological profile and film forming behaviour.
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    Do model polymer therapeutics sufficiently diffuse through articular cartilage to be a viable therapeutic route?
    (Taylor and Francis, 2017-09-21) Powell, Alison; Caterson, Bruce; Hughes, Claire; Paul, Alison; James, Craig; Hopkins, Stephen; Mansour, Omar T.; Griffiths, Peter
    The ability of a polymer therapeutic to access the appropriate subcellular location is crucial to its efficacy and is defined to a large part by the many and complex cellular biological and biochemical barriers such that a construct must traverse. It is shown here that model dextrin conjugates are able to pass through a cartilaginous extracellular matrix into chondrocytes, with little perturbation of the matrix structure, indicating that targeting of potential therapeutics through a cartilaginous extracellular matrix should be proven possible. Rapid chondrocytic targeting of drugs which require intra cellularisation for their activity and uniform extracellular concentrations of drugs with an extracellular target, is thus enabled though polymer conjugation.
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    Electrophoretic NMR characterisation of charged sidechain cationic polyelectrolytes and their interaction with the anionic surfactant, sodium dodecyl sulfate.
    (Langmuir, 2019) Mansour, Omar T.; Patel, Leesa; Crossman, Martin; Griffiths, Peter
    Oppositely charged polymers and surfactants show a complex phase behavior with large regions of solubility and insolubility dependent on the concentrations of the species present. Here, a series of quaternized hydroxyethyl cellulose (cationic) polymers have been characterized by pulsed-gradient spin–echo NMR (PGSE-NMR) and electrophoretic NMR (eNMR) in simple aqueous (D2O) solutions and in combination with the oppositely charged (anionic) surfactant, sodium dodecyl sulfate (SDS). Analysis of the effective charge on the polymer derived from both the eNMR and PGSE-NMR results yields a readily interpretable insight into the polymer behavior; the effective charge on the polymer at infinite dilution shows a linear relationship with the degree of modification. On addition of low concentrations of SDS, typically Csurf < 5 mM, the surfactant interacts with the charged polymers, leading to substantial changes in the dynamics of the system (polymer diffusion, viscosity). At these levels of surfactant addition, there is no macroscopic phase separation. Further, with the absence of an interaction with the parent, the uncharged polymer strongly suggests that the SDS only interacts with the charged moieties present on the functionalized side groups and not the polymer backbone. Ultimately, the charge on the soluble polymer/surfactant complex was found to depend linearly on the level of surfactant binding across a series of polymers with differing levels of modification with the charge becoming effectively zero at the macroscopic phase separation boundary.
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    Endocytic uptake, transport and macromolecular interactions of anionic PAMAM dendrimers within lung tissue
    (Springer, 2017-06-14) Morris, Christopher J.; Aljayyoussi, Ghaith; Mansour, Omar T.; Griffiths, Peter; Gumbleton, Mark
    Purpose: Polyamidoamine (PAMAM) dendrimers are a promising class of nanocarrier with applications in both small and large molecule drug delivery. Here we report a comprehensive evaluation of the uptake and transport pathways that contribute to the lung disposition of dendrimers. Methods: Anionic PAMAM dendrimers and control dextran probes were applied to an isolated perfused rat lung (IPRL) model and lung epithelial monolayers. Endocytosis pathways were examined in primary alveolar epithelial cultures by confocal microscopy. Molecular interactions of dendrimers with protein and lipid lung fluid components were studied using small angle neutron scattering (SANS). Results: Dendrimers were absorbed across the intact lung via a passive, size-dependent transport pathway at rates slower than dextrans of similar molecular sizes. SANS investigations of concentration-dependent PAMAM transport in the IPRL confirmed no aggregation of PAMAMs with either albumin or dipalmitoylphosphatidylcholine lung lining fluid components. Distinct endocytic compartments were identified within primary alveolar epithelial cells and their functionality in the rapid uptake of fluorescent dendrimers and model macromolecular probes was confirmed by co-localisation studies. Conclusions: PAMAM dendrimers display favourable lung biocompatibility but modest lung to blood absorption kinetics. These data support the investigation of dendrimer-based carriers for controlled-release drug delivery to the deep lung.
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    Interaction of Low Molecular Weight Poly(diallyldimethylammonium chloride) and Sodium Dodecyl Sulfate in Low Surfactant–Polyelectrolyte Ratio, Salt-Free Solutions
    (ACS Publications, 2020-07-15) Patel, Leesa; Mansour, Omar T.; Bryant, Hannah; Abdullahi, Wasiu; Dalgliesh, Robert; Griffiths, Peter
    Coacervation is widely used in formulations to induce a beneficial character to the formulation, but nonequilibrium effects are often manifest. Electrophoretic NMR (eNMR), pulsed-gradient spin-echo NMR (PGSE-NMR), and small-angle neutron scattering (SANS) have been used to quantify the interaction between low molecular cationic poly(diallyldimethylammonium chloride) (PDADMAC) and the anionic surfactant sodium dodecyl sulfate (SDS) in aqueous solution as a model for the precursor state to such nonequilibrium processes. The NMR data show that, within the low surfactant concentration one-phase region, an increasing surfactant concentration leads to a reduction in the charge on the polymer and a collapse of its solution conformation, attaining minimum values coincident with the macroscopic phase separation boundary. Interpretation of the scattering data reveals how the rodlike polymer changes over the same surfactant concentration window, with no discernible fingerprint of micellar type aggregates, but rather with the emergence of disklike and lamellar structures. At the highest surfactant concentration, the emergence of a weak Bragg peak in both the polymer and surfactant scattering suggests these precursor disk and lamellar structures evolve into paracrystalline stacks which ultimately phase separate. Addition of the nonionic surfactant hexa(ethylene glycol) monododecyl ether (C12E6) to the system seems to have little effect on the PDADMAC/SDS interaction as determined by NMR, merely displacing the observed behavior to lower SDS concentrations, commensurate with the total SDS present in the system. In other words, PDADMAC causes the disruption of the mixed SDS/C12E6 micelle, leading to SDS-rich PDADAMC/surfactant complexes coexisting with C12E6-rich micelles in solution.
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    Probing competitive interactions in quaternary formulations
    (2015-04-30) Mansour, Omar T.; Cattoz, Beatrice N.; Heenan, Richard K.; King, Stephen M.; Griffiths, Peter
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    Quantifying the micellar structure formed from hydrocarbon-fluorocarbon surfactants
    (Elsevier, 2015-12-30) Et-Tarhouni, Zaineb O.; Carter, Emma; Murphy, Damien M.; Griffiths, Peter C.; Mansour, Omar T.; King, Stephen; Paul, Alison
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    Segregation versus interdigitation in highly dynamic polymer/surfactant layers
    (MDPI, 2019-01-10) Mansour, Omar T.; Cattoz, Beatrice; Beaube, Manon; Heenan, Richard K.; Schweins, Ralf; Hurcom, Jamie; Griffiths, Peter
    Abstract Many polymer/surfactant formulations involve a trapped kinetic state that provides some beneficial character to the formulation. However, the vast majority of studies on formulations focus on equilibrium states. Here, nanoscale structures present at dynamic interfaces in the form of air-in-water foams are explored, stabilised by mixtures of commonly used non-ionic, surface active block copolymers (Pluronic®) and small molecule ionic surfactants (sodium dodecylsulfate, SDS, and dodecyltrimethylammonium bromide, C12TAB). Transient foams formed from binary mixtures of these surfactants shows considerable changes in stability which correlate with the strength of the solution interaction which delineate the interfacial structures. Weak solution interactions reflective of distinct coexisting micellar structures in solution lead to segregated layers at the foam interface, whereas strong solution interactions lead to mixed structures both in bulk solution, forming interdigitated layers at the interface