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  1. Article ; Online: A Stability Indicating HPLC Assay Method for Analysis of Rivastigmine Hydrogen Tartrate in Dual-Ligand Nanoparticle Formulation Matrices and Cell Transport Medium

    Naz Hasan Huda / Bhawna Gauri / Heather A. E. Benson / Yan Chen

    Journal of Analytical Methods in Chemistry, Vol

    2018  Volume 2018

    Abstract: The objective of this study was to develop and validate a method for quantitative analysis of rivastigmine hydrogen tartrate (RHT) in dual-ligand polymeric nanoparticle formulation matrices, drug release medium, and cellular transport medium. An ... ...

    Abstract The objective of this study was to develop and validate a method for quantitative analysis of rivastigmine hydrogen tartrate (RHT) in dual-ligand polymeric nanoparticle formulation matrices, drug release medium, and cellular transport medium. An isocratic HPLC analysis method using a reverse phase C18 column and a simple mobile phase without buffer was developed, optimised, and fully validated. Analyses were carried out at a flow rate of 1.5 mL/min at 50°C and monitored at 214 nm. This HPLC method exhibited good linearity, accuracy, and selectivity. The recovery (accuracy) of RHT from all matrices was greater than 99.2%. The RHT peak detected in the samples of a forced degradation study, drug loading study, release study, and cellular transport study was pure and free of matrix interference. The limit of detection (LOD) and limit of quantification (LOQ) of the assay were 60 ng/mL and 201 ng/mL, respectively. The method was rugged with good intra- and interday precision. This stability indicating HPLC method was selective, accurate, and precise for analysing RHT loading and its stability in nanoparticle formulation, RHT release, and cell transport medium.
    Keywords Analytical chemistry ; QD71-142
    Subject code 540
    Language English
    Publishing date 2018-01-01T00:00:00Z
    Publisher Hindawi Limited
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: A randomised pilot equivalence trial to evaluate diamagnetically enhanced transdermal delivery of key ground substance components in comparison to an established transdermal non-steroidal anti-inflammatory formulation in males with prior knee injury.

    Bill Vicenzino / Peter Lawrenson / Asaduzzaman Khan / Aiofe Stephenson / Luke Heales / Heather A E Benson / Anthony Wright

    PLoS ONE, Vol 14, Iss 2, p e

    2019  Volume 0211999

    Abstract: Objective This pilot study assessed the efficacy of a knee guard device, which used magnetophoresis to transdermally deliver Glucosamine, Chondroitin and Hyaluronic Acid in a cohort of individuals with prior knee injury. The aim was to determine if the ... ...

    Abstract Objective This pilot study assessed the efficacy of a knee guard device, which used magnetophoresis to transdermally deliver Glucosamine, Chondroitin and Hyaluronic Acid in a cohort of individuals with prior knee injury. The aim was to determine if the change in physical function and pain with the knee guard device was equivalent to the change produced by an established topical NSAID formulation containing diclofenac sodium 1%. Methods A randomized, controlled, equivalence trial evaluated outcomes following treatment with the knee guard device or NSAID formulation. The study recruited 114 male participants (aged 40-55 years). Participants were randomly allocated to wear the knee guard device or to use a NSAID gel daily for two weeks. The primary outcomes were the knee injury osteoarthritis function score (KOOS-F) and an aggregated function score (AFS). The lower extremity functional scale (LEFS), pain numerical rating scale (PNRS), global rating of change (GROC) and other KOOS scores were also evaluated. Results Multiple linear regression analyses indicated that there were no significant differences between the interventions for changes in the primary outcomes of AFS and KOOS_F. The 95% confidence interval (-2.89 to 5.15) of the estimated treatment difference for KOOS-F was within the lower (-5.61) and upper (5.61) bounds of the 7% equivalence margin for that measure, The mean value for the AFS was within, but the 95% CI (-3.11 to 7.37) exceeded the 7% equivalence margin (-2.97 to 2.97) for that measure. There was a significant difference in PNRS, which favored the knee guard device. Conclusion The knee guard device demonstrated equivalence for the KOOS-F measure but not the AFS measure of function over the two week trial period when compared to a widely available NSAID gel that has been shown to be superior to placebo. The knee guard produced a greater reduction in pain report (p = 0.002) than the NSAID gel. Users of the knee guard device experienced more skin irritation than participants using the NSAID gel. Further research is required to fully evaluate the therapeutic potential of this innovative treatment approach.
    Keywords Medicine ; R ; Science ; Q
    Subject code 796
    Language English
    Publishing date 2019-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Synthesis and Characterization of Novel Copolymeric Resveratrol Conjugates

    Yan-Jing Ng / Heather A. E. Benson / David H. Brown / Yan Chen

    Journal of Chemistry, Vol

    2015  Volume 2015

    Keywords Science ; Q ; Chemistry ; QD1-999
    Publishing date 2015-01-01T00:00:00Z
    Publisher Hindawi Publishing Corporation
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Synthesis and Characterization of Novel Copolymeric Resveratrol Conjugates

    Yan-Jing Ng / Heather A. E. Benson / David H. Brown / Yan Chen

    Journal of Chemistry, Vol

    2015  Volume 2015

    Abstract: Resveratrol (RSV), naturally found in plants, is known to have health benefits and has been proposed as a potential anticancer and cardioprotective drug. However, due to its molecular structure, it undergoes rapid metabolism in the body resulting in low ... ...

    Abstract Resveratrol (RSV), naturally found in plants, is known to have health benefits and has been proposed as a potential anticancer and cardioprotective drug. However, due to its molecular structure, it undergoes rapid metabolism in the body resulting in low bioavailability. Novel polymeric methoxy-poly(ethylene glycol)-block-poly(ε-caprolactone) (mPEG-PCL) RSV conjugates with varying PCL chain lengths have been synthesised and formulated into micelles and/or nanoparticles for preliminary in vitro stability studies. RSV conjugated with mPEG2000-PCL9500 was found to have improved solubility and stability of RSV as compared to RSV alone. The length of the PCL chain was found to affect the micelle formation, hence the stability in physiological buffers and rat plasma.
    Keywords Chemistry ; QD1-999
    Language English
    Publishing date 2015-01-01T00:00:00Z
    Publisher Hindawi Limited
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Stabilization of resveratrol in blood circulation by conjugation to mPEG and mPEG-PLA polymers

    Basavaraj Siddalingappa / Heather A E Benson / David H Brown / Kevin T Batty / Yan Chen

    PLoS ONE, Vol 10, Iss 3, p e

    investigation of conjugate linker and polymer composition on stability, metabolism, antioxidant activity and pharmacokinetic profile.

    2015  Volume 0118824

    Abstract: Resveratrol is naturally occurring phytochemical with diverse biological activities such as chemoprevention, anti-inflammatory, anti-cancer, anti-oxidant. But undergoes rapid metabolism in the body (half life 0.13h). Hence Polymer conjugation utilizing ... ...

    Abstract Resveratrol is naturally occurring phytochemical with diverse biological activities such as chemoprevention, anti-inflammatory, anti-cancer, anti-oxidant. But undergoes rapid metabolism in the body (half life 0.13h). Hence Polymer conjugation utilizing different chemical linkers and polymer compositions was investigated for enhanced pharmacokinetic profile of resveratrol. Ester conjugates such as α-methoxy-ω-carboxylic acid poly(ethylene glycol) succinylamide resveratrol (MeO-PEGN-Succ-RSV) (2 and 20 kDa); MeO-PEG succinyl ester resveratrol (MeO-PEGO-Succ-RSV) (2 kDa); α-methoxy poly(ethylene glycol)-co-polylactide succinyl ester resveratrol (MeO-PEG-PLAO-Succ-RSV) (2 and 6.6kDa) were prepared by carbodiimide coupling reactions. Resveratrol-PEG ethers (2 and 5 kDa) were synthesized by alkali-mediated etherification. All polymer conjugates were fully characterized in vitro and the pharmacokinetic profile of selected conjugates was characterized in rats. Buffer and plasma stability of conjugates was dependent on polymer hydrophobicity, aggregation behavior and PEG corona, with MeO-PEG-PLAO-Succ-RSV (2 kDa) showing a 3h half-life in rat plasma in vitro. Polymer conjugates irrespective of linker chemistry protected resveratrol against metabolism in vitro. MeO-PEG-PLAO-Succ-RSV (2 kDa), Resveratrol-PEG ether (2 and 5 kDa) displayed improved pharmacokinetic profiles with significantly higher plasma area under curve (AUC), slower clearance and smaller volume of distribution, compared to resveratrol.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2015-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Space- and time-resolved investigation on diffusion kinetics of human skin following macromolecule delivery by microneedle arrays

    Jonathan C. J. Wei / Isha N. Haridass / Michael L. Crichton / Yousuf H. Mohammed / Stefano C. Meliga / Washington Y. Sanchez / Jeffrey E. Grice / Heather A. E. Benson / Michael S. Roberts / Mark A. F. Kendall

    Scientific Reports, Vol 8, Iss 1, Pp 1-

    2018  Volume 15

    Abstract: Abstract Microscale medical devices are being developed for targeted skin delivery of vaccines and the extraction of biomarkers, with the potential to revolutionise healthcare in both developing and developed countries. The effective clinical development ...

    Abstract Abstract Microscale medical devices are being developed for targeted skin delivery of vaccines and the extraction of biomarkers, with the potential to revolutionise healthcare in both developing and developed countries. The effective clinical development of these devices is dependent on understanding the macro-molecular diffusion properties of skin. We hypothesised that diffusion varied according to specific skin layers. Using three different molecular weights of rhodamine dextran (RD) (MW of 70, 500 and 2000 kDa) relevant to the vaccine and therapeutic scales, we deposited molecules to a range of depths (0–300 µm) in ex vivo human skin using the Nanopatch device. We observed significant dissipation of RD as diffusion with 70 and 500 kDa within the 30 min timeframe, which varied with MW and skin layer. Using multiphoton microscopy, image analysis and a Fick’s law analysis with 2D cartesian and axisymmetric cylindrical coordinates, we reported experimental trends of epidermal and dermal diffusivity values ranging from 1–8 µm2 s−1 to 1–20 µm2 s−1 respectively, with a significant decrease in the dermal-epidermal junction of 0.7–3 µm2 s−1. In breaching the stratum corneum (SC) and dermal-epidermal junction barriers, we have demonstrated practical application, delivery and targeting of macromolecules to both epidermal and dermal antigen presenting cells, providing a sound knowledge base for future development of skin-targeting clinical technologies in humans.
    Keywords Medicine ; R ; Science ; Q
    Subject code 571
    Language English
    Publishing date 2018-12-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Microneedle enhanced delivery of cosmeceutically relevant peptides in human skin.

    Yousuf H Mohammed / Miko Yamada / Lynlee L Lin / Jeffrey E Grice / Michael S Roberts / Anthony P Raphael / Heather A E Benson / Tarl W Prow

    PLoS ONE, Vol 9, Iss 7, p e

    2014  Volume 101956

    Abstract: Peptides and proteins play an important role in skin health and well-being. They are also found to contribute to skin aging and melanogenesis. Microneedles have been shown to substantially enhance skin penetration and may offer an effective means of ... ...

    Abstract Peptides and proteins play an important role in skin health and well-being. They are also found to contribute to skin aging and melanogenesis. Microneedles have been shown to substantially enhance skin penetration and may offer an effective means of peptide delivery enhancement. The aim of this investigation was to assess the influence of microneedles on the skin penetration of peptides using fluorescence imaging to determine skin distribution. In particular the effect of peptide chain length (3, 4, 5 amino acid chain length) on passive and MN facilitated skin penetration was investigated. Confocal laser scanning microscopy was used to image fluorescence intensity and the area of penetration of fluorescently tagged peptides. Penetration studies were conducted on excised full thickness human skin in Franz type diffusion cells for 1 and 24 hours. A 2 to 22 fold signal improvement in microneedle enhanced delivery of melanostatin, rigin and pal-KTTKS was observed. To our knowledge this is the first description of microneedle enhanced skin permeation studies on these peptides.
    Keywords Medicine ; R ; Science ; Q
    Subject code 571
    Language English
    Publishing date 2014-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article: In vivo production of novel vitamin D2 hydroxy-derivatives by human placentas, epidermal keratinocytes, Caco-2 colon cells and the adrenal gland

    Slominski, Andrzej T / Charles R. Yates / Edith K.Y. Tang / Haleem Z. Shehabi / Heather A.E. Benson / Igor Semak / Jin Wang / Robert C. Tuckey / Tae-Kang Kim / Wei Li / Zongtao Lin

    Molecular and Cellular Endocrinology. 2014 Mar. 05, v. 383

    2014  

    Abstract: We investigated the metabolism of vitamin D2 to hydroxyvitamin D2 metabolites ((OH)D2) by human placentas ex-utero, adrenal glands ex-vivo and cultured human epidermal keratinocytes and colonic Caco-2 cells, and identified 20(OH)D2, 17,20(OH)2D2, 1,20(OH) ...

    Abstract We investigated the metabolism of vitamin D2 to hydroxyvitamin D2 metabolites ((OH)D2) by human placentas ex-utero, adrenal glands ex-vivo and cultured human epidermal keratinocytes and colonic Caco-2 cells, and identified 20(OH)D2, 17,20(OH)2D2, 1,20(OH)2D2, 25(OH)D2 and 1,25(OH)2D2 as products. Inhibition of product formation by 22R-hydroxycholesterol indicated involvement of CYP11A1 in 20- and 17-hydroxylation of vitamin D2, while use of ketoconazole indicated involvement of CYP27B1 in 1α-hydroxylation of products. Studies with purified human CYP11A1 confirmed the ability of this enzyme to convert vitamin D2 to 20(OH)D2 and 17,20(OH)2D2. In placentas and Caco-2 cells, production of 20(OH)D2 was higher than 25(OH)D2 while in human keratinocytes the production of 20(OH)D2 and 25(OH)D2 were comparable. HaCaT keratinocytes showed high accumulation of 1,20(OH)2D2 relative to 20(OH)D2 indicating substantial CYP27B1 activity. This is the first in vivo evidence for a novel pathway of vitamin D2 metabolism initiated by CYP11A1 and modified by CYP27B1, with the product profile showing tissue- and cell-type specificity.
    Keywords adrenal glands ; colon ; ergocalciferol ; human cell lines ; humans ; keratinocytes ; ketoconazole ; metabolites ; placenta ; vitamin metabolism
    Language English
    Dates of publication 2014-0305
    Size p. 181-192.
    Publishing place Elsevier Ireland Ltd
    Document type Article
    ZDB-ID 187438-x
    ISSN 1872-8057 ; 0303-7207
    ISSN (online) 1872-8057
    ISSN 0303-7207
    DOI 10.1016/j.mce.2013.12.012
    Database NAL-Catalogue (AGRICOLA)

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