Nigel K H Slater

University of Cambridge, Cambridge, England, United Kingdom

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Publications (113)424.34 Total impact

  • S.A. Mercado · N.K.H. Slater

    No preview · Article · Dec 2015 · Cryobiology
  • S.A. Mercado · N.K.H. Slater
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    ABSTRACT: The use of amphipathic pH-responsive polymers to transport sugars across cell membranes has been shown to improve the cryopreservation of mammalian cells. However, the effect of these polymers on cell viability and morphology has not yet been thoroughly analysed. In this study, the objective was to investigate the functional and structural effects of an amphipathic polymer, PP-50, upon an osteosarcoma cell line (SAOS-2). Cellular growth curves confirmed similar doubling times in PP-50 treated cells and untreated cells. PP-50 concentrations (10–2000 μg/ml) were well tolerated by cells after 2, 24 and 48 h of incubation, as measured by mitochondrial enzyme activity and Lactate Dehydrogenase release. Analysis by flow cytometry demonstrated that PP-50 did not induce any additional apoptosis or necrosis in polymer treated cells compared to untreated cells. Phase contrast, confocal and transmission electron microscopy analysis of PP-50 treated cells revealed no signs of morphological changes, with cells maintaining their nucleus size and membrane integrity after treatment. PP-50 was shown to have no negative cellular effects, which is a critical characteristic of polymers towards use in cryopreservation and biomedical applications. In addition, the methodology and protocols established in this work provided a robust and comprehensive analysis of PP-50’s cellular effects, thus making them well suited for determining these effects in mammalian cells exposed to other polymers intended for biological applications.
    No preview · Article · Nov 2015 · European Polymer Journal
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    ABSTRACT: AbstractA micro-capillary film has been developed that offers the potential for an at-line analytical tool for rapid aggregate analysis during biopharmaceutical antibody production. A non-porous walled micro-capillary film (NMCF) with cation exchange functionality was demonstrated to act as a chromatography medium that could be operated with high linear fluid velocities and was highly resistant to blockage by entrained particulates, including cells. The NMCF containing 19 parallel microcapillaries was prepared using a melt extrusion process from poly(ethylene-vinyl alcohol) copolymer (EVOH). The NMCF-EVOH was modified to have cation-exchange functionality (NMCF-EVOH-SP) and shown to differentially bind monomer and aggregated species of IgG antibody directly from a bioreactor. The use of NMCF-EVOH-SP to quantify aggregate concentrations in monoclonal antibody preparations in less than 20 minutes was demonstrated.
    Full-text · Article · Oct 2015 · mAbs
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    ABSTRACT: We report the encapsulation of the hydrophilic model molecule calcein in the Zr-based MOF UiO-66, followed by amorphization of the framework by ball-milling. We show controlled release of calcein over more than 30 days, compared with the 2 day release period from crystalline UiO-66.
    No preview · Article · Jul 2015 · Chemical Communications
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    ABSTRACT: This research explores the photofermentation of glycerol to hydrogen by Rhodopseudomonas palustris, with the objective to maximise hydrogen production. Two piecewise models are designed to simulate the entire growth phase of R. palustris; a challenge that few dynamic models can accomplish. The parameters in both models were fitted by the present batch experiments through the solution of the underlying optimal control problems by means of stable and accurate discretisation techniques. It was found that an initial glutamate to glycerol ratio of 0.25 was optimal and was independent of the initial biomass concentration. The glycerol conversion efficiency was found to depend on initial biomass concentration and its computational peak is 64.4%. By optimising a 30-day industrially relevant batch process, the hydrogen productivity was improved to be 37.7 mL g biomass−1 h−1 and the glycerol conversion efficiency was maintained at 58%. The models can then be applied as the connection to transfer biohydrogen production from laboratory scale into industrial scale.
    Full-text · Article · Jul 2015 · Chemical Engineering Science
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    Full-text · Dataset · Apr 2015
  • Radu Alexandru Lazar · Isphita Mandal · Nigel K. H. Slater
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    ABSTRACT: Micro-capillary film (MCF) membranes are effective platforms for bioseparations and viable alternatives to established packed bed and membrane substrates at the analytical and preparative chromatography scales. Single hollow fibre (HF) MCF membranes with varied microstructures were produced in order to evaluate the effect of the bore fluid composition used during hollow fibre extrusion on their structure and performance as cation-exchange adsorbers. Hollow fibres were fabricated from ethylene-vinyl alcohol (EVOH) copolymer through solution extrusion followed by nonsolvent induced phase separation (NIPS) using bore fluids of differing composition (100wt.% N-methyl-2-pyrrolidone (NMP), 100wt.% glycerol, 100wt.% water). All HFs displayed highly microporous and mesoporous microstructures, with distinct regions of pore size <1μm, 5-15μm and up to 50μm in diameter, depending upon proximity to the bore fluid. Scanning electron microscopy (SEM) revealed skins of pore size <1μm at the inner surface of HFs produced with water and glycerol, while NMP bore fluid resulted in a skinless inner HF surface. The HFs were modified for chromatography by functionalising the polymer surface hydroxyl groups with sulphonic acid (SP) groups to produce cation-exchange adsorbers. The maximum binding capacities of the HFs were determined by frontal analysis using lysozyme solutions (0.05-100mgml(-1)) for a flow rate of 1.0mlmin(-1). The NMP-HF-SP module displayed the largest maximum lysozyme binding capacity of all the fibres produced (40.3mg lysozyme/ml adsorbent volume), a nearly 2-fold increase over the glycerol and 10-fold increase over the water variants at the same sample flow rate. The importance of NMP as a bore fluid to hollow fibre membrane performance as a result of inner surface porosity was established with a view to applying this parameter for the optimisation of multi-capillary MCF performance in future studies. Copyright © 2015 Elsevier B.V. All rights reserved.
    No preview · Article · Mar 2015 · Journal of Chromatography A
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    ABSTRACT: Tablet disintegration characterisation is used in pharmaceutical research, development, and quality control. Standard methods used to characterise tablet disintegration are often dependent on visual observation in measurement of disintegration times. This presents a challenge for disintegration studies of tablets in opaque, physiologically relevant media that could be useful for tablet formulation optimisation. In this study is explored an application of texture analysis disintegration testing, a non-visual, quantitative means of determining tablet disintegration end point, by analysing the disintegration behaviour of two tablet formulations in opaque media. In this study, the disintegration behaviour of one tablet formulation manufactured in-house, and Sybedia Flashtab placebo tablets in water, bovine, and human milk were characterised. A novel method is presented to characterise the disintegration process and to quantify the disintegration end points of the tablets in various media using load data generated by a texture analyser probe. The disintegration times in the different media were found to be statistically different (P<0.0001) from one another for both tablet formulations using one-way ANOVA. Using the Tukey post-hoc test, the Flashtab placebo tablets were found not to have statistically significant disintegration times from each other in human versus bovine milk (adjusted P value 0.1685). Copyright © 2015. Published by Elsevier B.V.
    Full-text · Article · Mar 2015 · International Journal of Pharmaceutics
  • Rebekah Scheuerle · Stephen Gerrard · Nigel Slater
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    ABSTRACT: Few infant drug delivery methods are tailored for dosing and administering oral medications to breastfeeding infants, especially in resource-limited settings. The infant annual mortality rate exceeds 4.8 million annually, and many leading causes of child mortality are largely preventable with safe and easy to administer medications. Therefore, there is a need for development of novel infant drug delivery and dosing methods. In response to this need, we are developing the nipple shield delivery system (NSDS) and a method of testing the device in vitro. The NSDS, when worn by a mother during breastfeeding, releases medications or nutrients from a tablet it contains, into milk consumed by the infant, simultaneously dosing and delivering the active pharmaceutical ingredients. To test this device in vitro, a breastfeeding simulation apparatus is needed to mimic the process of maternal lactation and infant behaviours during breastfeeding. We have developed a simulation apparatus with functionalities for mimicking lactation flow rates through a physiologically accurate breast mimic and for monitoring and mimicking infant suckling behaviours including sucking rate and imparted pressures. The current aim of our research is to increase the physiological accuracy of the apparatus, by developing a method to also test the potential impact of infant tongue use on the NSDS during breastfeeding. An infant tongue mimic was constructed based on modifications to a peristaltic pump. A metal plate was attached to mimic an infant upper palate, and a piezoresistive sensor was placed in the system to measure the pressure exerted by the tongue mimic and palate mimic on tablets contained in tubing placed in between. The mimic, through peristaltic motion and by applying a range of pressures potentially imparted by an infant tongue, is then used to test the impact of infant tongue movements on release rates of material which could be contained in an NSDS under flow conditions similar to those during breastfeeding. The release of the model compound sulphorhodamine b from a potential NSDS tablet formulation was quantified from the tongue mimic system at various tongue mimic speeds and applied pressures. Greater than 76% percent release occurred within 600 seconds, well within the 16.6 minute length of an average breastfeed, for tongue mimic contact rates of 0-240 contacts per minute into water flowing at the average expression rate of 6 mL/min. Preliminary results indicate the tongue mimic system can impart pressures and mimic contact rates in the ranges of those of an infant tongue on potential tablets which are being developed and screened for use in the NSDS. This tongue mimic system will improve the accuracy of our breastfeeding simulation apparatus for further in vitro testing of the NSDS as we continue developing this method for oral delivery of medications to infants.
    No preview · Conference Paper · Nov 2014
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    I. Mandal · M. J. Townsend · N. J. Darton · S. Bonyadi · N.K.H. Slater
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    ABSTRACT: Opportunities exist in preparative chromatography for alternative chromatography media that possess high binding capacity and throughput, but are also economically feasible for single use disposability and avoid column packing. An ion-exchange functionalised, microporous walled micro-capillary film (MMCF), has been developed as a module for cation-exchange separation of proteins. A MMCF module has been operated on a standard AKTA chromatography system at pressures up to 1.5 MPa and superficial flow velocities up to 54,000 cm h−1. The dynamic binding capacity of the MMCF module at 10% breakthrough was 13.8 mg lysozyme/ml adsorbent volume, which is comparable to the capacity of current commercial adsorbents. Frontal analysis studies using a mixture of lysozyme and bovine serum albumin (BSA) have shown that lysozyme can be isolated free of BSA to the limit of detection of the SDS gel assay used. 98.8% of the total sample eluted was the target protein lysozyme with only 1.2% BSA impurity. MMCF may thus be a viable chromatographic medium for preparative protein chromatography.
    Full-text · Article · Sep 2014 · Journal of Membrane Science
  • Krishnaa Mahbubani · Nigel K.H. Slater

    No preview · Article · Jul 2014 · New Biotechnology
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    D J McNally · D Darling · F Farzaneh · P R Levison · N K H Slater
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    ABSTRACT: The ability of an anion exchange membrane to purify a γ-retrovirus was assessed and optimised with respect to different loading and wash buffers. Recoveries of infectious virus greater than 50% were consistently obtained, while specific titre was increased up to one thousand fold when compared to the material loaded. Specific proteins removed and retained by this optimised process were identified by mass spectrometry. It was possible to successfully bind and elute the equivalent of 1.27×10(8)Ifu/ml of ion exchange membrane. This could then be highly concentrated, with infectious virus concentrated to a maximum of 420-fold compared to the load.
    Full-text · Article · Mar 2014 · Journal of Chromatography A
  • Polly Hr Keen · Nigel K H Slater · Alexander Francis Routh
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    ABSTRACT: Aqueous core colloidosomes encapsulating the enzyme amylase were manufactured with a shell comprising polymer latex particles of diameter 153 nm. The colloidosomes were sealed with calcium carbonate by precipitation between an inner phase of Na2CO3 and an outer phase of CaCl2. This seal allowed the retention of small molecules, such as dyes, as well as larger enzyme molecules, for several months. The encapsulated material could be released by dissolution of the CaCO3 with acid, upon a large dilution in water, or by applying a sufficient shear. The degree of release could be controlled since the greater the mass of CaCO3 precipitated onto the colloidosome shell, the greater the dilution or shear required to achieve release. The calcium carbonate seal protected encapsulated amylase from the detrimental effects of components in a liquid laundry detergent for several months so that, on triggered release, the enzyme retained its high activity.
    No preview · Article · Feb 2014 · Langmuir
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    Stephen E Gerrard · Mine Orlu-Gul · Catherine Tuleu · Nigel K H Slater
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    ABSTRACT: An apparatus was designed to mimic lactation from a human breast. It was used to determine the influence of milk fat content and flow rate, and suction pulse rate of a breastfeeding infant upon the release of a model compound from a nipple shield delivery system (NSDS). The NSDS would be worn by a mother to deliver drugs and nutrients to her infant during breastfeeding. Sulforhodamine B dye (SB) was used as model compound and formulated as a dispersible tablet to be placed within the NSDS. Increasing suction pulse rate from 30 to 120 pulses/min clearly correlated with increased cumulative release of SB for the same volume of milk passed through the NSDS. No distinct correlation was found between flow rates (1, 5, and 8 mL/min) and SB release, possibly because of competing factors controlling release rate at different flow rates. A highly similar SB release rate into two fat content fluids (2.9 and 4.2 wt %) was observed for identical flow conditions. This proof of concept study outlines a novel method to mimic lactation from a breast, and future studies will lead to effective methods to identify key physiological factors that influence drug release from a NSDS. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci.
    Full-text · Article · Oct 2013 · Journal of Pharmaceutical Sciences
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    Krishnaa T Mahbubani · Nigel K H Slater · Alexander D Edwards
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    ABSTRACT: Enteric coated oral tablets or capsules can deliver dried live cells directly into the intestine. Previously, we found that a live attenuated bacterial vaccine acquired sensitivity to intestinal bile when dried, raising the possibility that although gastric acid can be bypassed, significant loss of viability might occur on release from an enteric coated oral formulations. Here we demonstrate that some food-grade lyophilised preparations of Lactobacillus casei and Lactobacillus salivarius also show temporary bile sensitivity that can be rapidly reversed by rehydration. To protect dried cells from temporary bile sensitivity, we propose using bile acid adsorbing resins, such as cholestyramine, which are bile acid binding agents, historically used to lower cholesterol levels. Vcaps™ HPMC capsules alone provided up to 830-fold protection from bile. The inclusion of 50% w/w cholestyramine in Vcaps™ HPMC capsules resulted in release of up to 1700-fold more live Lactobacillus casei into simulated intestinal fluid containing 1% bile, when compared to dried cells added directly to bile. We conclude that delivery of dried live probiotic organisms to the intestine may be improved by providing protection from bile by addition of bile adsorbing resins and the use of HPMC capsules.
    Full-text · Article · Sep 2013 · New Biotechnology
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    ABSTRACT: For stem cell therapy to become a routine reality, one of the major challenges to overcome is their storage and transportation. Currently this is achieved by cryopreserving cells utilising the cryoprotectant dimethyl sulfoxide (Me2SO). Me2SO is toxic to cells, leads to loss of cell functionality, and can produce severe side effects in patients. Potentially, cells could be frozen using the cryoprotectant trehalose if it could be delivered into the cells at a sufficient concentration. The novel amphipathic membrane permeabilising agent PP-50 has previously been shown to enhance trehalose uptake by erythrocytes, resulting in increased cryosurvival. Here, this work was extended to the nucleated human cell line SAOS-2. Using the optimum PP-50 concentration and media osmolarity, cell viability post-thaw was 60 ± 2%. In addition, the number of metabolically active cells 24 h post-thaw, normalised to that before freezing, was found to be between 103 ± 4% and 91 ± 5%. This was found to be comparable to cells frozen using Me2SO. Although reduced (by 22 ± 2%, p = 0.09), the doubling time was found not to be statistically different to the non-frozen control. This was in contrast to cells frozen using Me2SO, where the doubling time was significantly reduced (by 41 ± 4%, p = 0.004). PP-50 mediated trehalose delivery into cells could represent an alternative cryopreservation protocol, suitable for research and therapeutic applications.
    Full-text · Article · Sep 2013 · Cryobiology
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    ABSTRACT: The infectivity of high-titer, cell-free HIV in culture media and human milk is rapidly reduced upon exposure to polyethylene slides painted with the linear hydrophobic polycation N,N-dodecyl,methyl-polyethylenimine (DMPEI). Accompanying viral p24 protein and free viral RNA analysis of solutions exposed to DMPEI-coated surfaces suggest that virion attachment to the polycationic surface and its subsequent inactivation are the likely mechanism of this phenomenon. Biotechnol. Bioeng. © 2013 Wiley Periodicals, Inc.
    Full-text · Article · Jul 2013 · Biotechnology and Bioengineering
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    ABSTRACT: The use of small interfering RNAs (siRNAs) to down-regulate the expression of disease-associated proteins carries significant promise for the treatment of a variety of clinical disorders. One of the main barriers to the widespread clinical use of siRNAs, however, is their entrapment and degradation within the endolysosomal pathway of target cells. Here we report the trafficking and function of PP75, a non-toxic, biodegradable, lipid membrane disruptive anionic polymer composed of phenylalanine derivatized poly(L-lysine iso-phthalamide). PP75 is readily endocytosed by cells, safely permeabilizes endolysosomes in a pH dependent manner and facilitates the transfer of co-endocytosed materials directly into the cytoplasm. The covalent attachment of siRNAs to PP75 using disulfide linkages generates conjugates that effectively traffic siRNAs to the cytoplasm of target cells both in vitro and in vivo. In a subcutaneous malignant glioma tumor model, a locally delivered PP75-stathmin siRNA conjugate decreases stathmin expression in tumor cells and, in combination with the nitrosourea chemotherapy carmustine, is highly effective at inhibiting tumor growth. PP75 may be clinically useful for the local delivery of siRNAs, in particular for the treatment of solid tumors.
    Full-text · Article · Feb 2013 · Advanced Functional Materials
  • Polly Hr Keen · Nigel K H Slater · Alexander Francis Routh
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    ABSTRACT: Polymeric colloidosomes encapsulating viable lactic acid bacteria were prepared. An aqueous suspension of 153 nm poly(methyl methacrylate-co-butylacrylate) latex particles plus Lactobacillus crispatus was emulsified in a continuous phase of sunflower oil. By adding a small amount of ethanol and salt to the oil phase the latex particles at the surface of the emulsion droplets aggregate to form the colloidosome shells. The colloidosomes have been examined using optical, confocal and scanning electron microscopies. The viability of the bacteria was tested using fluorescent molecular probes. The encapsulated lactic acid bacteria were able to metabolize glucose from solution and produce acid albeit at a slower rate compared to unencapsulated microbes. This demonstrates transport limitation through the colloidosome shell and restriction of the cellular metabolism due to encapsulation. Protection of the bacteria by encapsulation in colloidosomes was also demonstrated; a significantly larger number of encapsulated bacteria maintained viability in simulated stomach conditions compared to unencapsulated microbes.
    No preview · Article · Oct 2012 · Langmuir
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    ABSTRACT: A new disposable adsorbent material for fast anion-exchange capture of nano-complexes without prefiltering, clarification or pre-processing of samples was developed based on plastic microcapillary films (MCFs). An MCF containing 19 parallel microcapillaries, each with a mean internal diameter of 142 ± 10 μm, was prepared using a melt extrusion process from an ethylene-vinyl alcohol copolymer (EVOH). The MCF internal surfaces were functionalised using branched chain chemistries to attach quaternary amine groups producing an anion-exchange adsorbent. The purification of nano-complexes using this newly fabricated MCF-EVOH-Q was successfully demonstrated with the capture of lentivirus from pre-filtered culture harvest. This 5m chromatographic substrate was found to bind and elute ∼40% of bound lentivirus or 2.5 × 10(6)infectious units (ifu). The unique properties of this chromatographic substrate that allow the passage of large particulates was further demonstrated with the capture of lentiviral particles from unfiltered un-processed culture media containing cells and cell debris. Using this approach, 56% or 1 × 10(7)ifu of captured lentivirus was eluted. A device based on this new material might be used at an early stage in clinical lentiviral production to harvest lentiviral particles, directly from bioreactors.
    No preview · Article · Jun 2012 · Journal of Chromatography A

Publication Stats

2k Citations
424.34 Total Impact Points

Institutions

  • 2000-2015
    • University of Cambridge
      • Department of Chemical Engineering and Biotechnology
      Cambridge, England, United Kingdom
  • 2010
    • University of Reading
      Reading, England, United Kingdom
  • 1996-1999
    • Aston University
      • Department of Chemical Engineering and Applied Chemistry
      Birmingham, England, United Kingdom