Browsing by Author "Gilbert, J"

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    Cytotoxicity and structural analyses of 2,2′‐bipyridine‐, 4,4′‐dimethyl‐2,2′‐bipyr­idine‐ and 2‐(2′‐pyridyl)quinoxalineplatinum(II) complexes
    (John Wiley and Sons, 2015-08-07) Pages, BJ; Zhang, YJ; Li, F; Sakoff, J; Gilbert, J; Aldrich-Wright, JR
    Platinum anticancer complexes incorporating 2,2′-bipyridine (bpy), 4,4′-dimethyl-2,2′-bipyridine (44Me2bpy) or 2-(2′-pyridyl)quinoxaline (2pq) as polyaromatic ligands and the S,S or R,R isomer of 1,2-diaminocyclohexane as ancillary ligands in the form [Pt(PL)(AL)]2+ have been synthesised and characterised. X-ray diffraction was used to elucidate the structure and stacking behaviour of the complexes, revealing interesting properties that may impact their biological activity. Pulsed gradient spin-echo NMR experiments elucidated the aggregation behaviour of these complexes in solution. The cytotoxicity of each complex was assessed against the L1210 murine leukaemia, HT29 human colon carcinoma and U87 human glioblastoma cell lines and compared to other complexes within this class. The complexes incorporating 44Me2bpy were found to be the most potent at inhibiting cell growth with IC50 values for the S,S isomer (0.13–0.5 μM) less than that for cisplatin (0.36–11 μM), oxaliplatin (0.9–1.8 μM) or carboplatin (>50 μM). Most complexes were found to be very effective against HT29 colon carcinoma cells. © 1999-2020 John Wiley & Sons, Inc.
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    Evolution of the structure of lipid nanoparticles for nucleic acid delivery: from in situ studies of formulation to colloidal stability
    (Elsevier, 2024-04-15) Gilbert, J; Sebastiani, F; Yanez Arteta, M; Terry, A; Fornell, A; Russell, RA; Mahmoudi, N; Nylander, T
    The development of lipid nanoparticle (LNP) based therapeutics for delivery of RNA has triggered the advance of new strategies for formulation, such as high throughput microfluidics for precise mixing of components into well-defined particles. In this study, we have characterised the structure of LNPs throughout the formulation process using in situ small angle x-ray scattering in the microfluidic chip, then by sampling in the subsequent dialysis process. The final formulation was investigated with small angle x-ray (SAXS) and neutron (SANS) scattering, dynamic light scattering (DLS) and cryo-TEM. The effect on structure was investigated for LNPs with a benchmark lipid composition and containing different cargos: calf thymus DNA (DNA) and two model mRNAs, polyadenylic acid (polyA) and polyuridylic acid (polyU). The LNP structure evolved during mixing in the microfluidic channel, however was only fully developed during the dialysis. The colloidal stability of the final formulation was affected by the type of incorporated nucleic acids (NAs) and decreased with the degree of base-pairing, as polyU induced extensive particle aggregation. The main NA LNP peak in the SAXS data for the final formulation were similar, with the repeat distance increasing from polyU
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    Investigating the cytotoxicity of platinum(II) complexes incorporating bidentate pyridyl-1,2,3-triazole “click” ligands
    (Elsevier B.V., 2016-12-01) Pages, BJ; Sakoff, J; Gilbert, J; Zhang, Y; Li, F; Preston, D; Crowley, JD; Aldrich-Wright, JR
    Six platinum(II) complexes of the type [Pt(PL)(AL)]2 +, where PL is a bidentate pyridyl-1,2,3-triazole “click” ligand and AL is the R,R or S,S isomer of 1.2-diaminocyclohexane, have been synthesised and characterised by several methods including elemental microanalysis, proton NMR spectroscopy and X-ray crystallography. The in vitro cytotoxicity of each complex was assessed in eleven cell lines, revealing moderate to good activity for complexes incorporating 2-(1-phenyl-1H-1,2,3-triazol-4-yl)pyridine. © 2016 Elsevier B.V.