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443 results on '"Whittaker, Michael R."'

3. Sustained endosomal release of a neurokinin-1 receptor antagonist from nanostars provides long-lasting relief of chronic pain

Author

Latorre, Rocco, Ramírez-Garcia, Paulina D., Hegron, Alan, Grace, James L., Retamal, Jeffri S., Shenoy, Priyank, Tran, Mai, Aurelio, Luigi, Flynn, Bernard, Poole, Daniel P., Klein-Cloud, Rafael, Jensen, Dane D., Davis, Thomas P., Schmidt, Brian L., Quinn, John F., Whittaker, Michael R., Veldhuis, Nicholas A., and Bunnett, Nigel W.

Published
2022
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7. The oxytocin antagonist cligosiban reduces human prostate contractility: Implications for the treatment of benign prostatic hyperplasia.

Author

Bester, Beatrix, Koslowa, Kristina, Gronau, Ann‐Catherine, Mietens, Andrea, Nowell, Cameron, Whittaker, Michael R., Pilatz, Adrian, Wagenlehner, Florian, Exintaris, Betty, and Middendorff, Ralf

Subjects
PROSTATE, BENIGN prostatic hyperplasia, OXYTOCIN, TRANSURETHRAL prostatectomy, OLDER men, SMOOTH muscle
Abstract

Background and Purpose: With increasing life expectancy, benign prostatic hyperplasia (BPH) consequently affects more ageing men, illustrating the urgent need for advancements in BPH therapy. One emerging possibility may be the use of oxytocin antagonists to relax smooth muscle cells in the prostate, similar to the currently used (although often associated with side effects) α1‐adrenoceptor blockers. Experimental Approach: For the first time we used live‐imaging, combined with a novel image analysis method, to investigate the multidirectional contractions of the human prostate and determine their changes in response to oxytocin and the oxytocin antagonists atosiban and cligosiban. Human prostate samples were obtained and compared from patients undergoing prostatectomy due to prostate cancer as well as from patients with transurethral resection of prostate tissue due to severe BPH. Key Results: The two cohorts of tissue samples showed spontaneous multidirectional contractions, which significantly increased after the addition of oxytocin. Different to atosiban, which showed ambiguous effects of short duration, only long‐acting cligosiban reliably prevented, as well as counteracted, any contractile oxytocin effect. Furthermore, cligosiban visibly reduced not only oxytocin‐induced contractions, but also showed intrinsic activity to relax prostatic tissue. Conclusion and implications: Thus, the oxytocin antagonist cligosiban could be an interesting candidate in the search for novel BPH treatment options. [ABSTRACT FROM AUTHOR]

Published
2024
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14. Functionalisation of brush polyethylene glycol polymers with specific lipids extends their elimination half-life through association with natural lipid trafficking pathways

Author

Abdallah, Mohammad, primary, Lin, Lihuan, additional, Styles, Ian K., additional, Mörsdorf, Alexander, additional, Grace, James L., additional, Gracia, Gracia, additional, Nowell, Cameron, additional, Quinn, John F., additional, Landersdorfer, Cornelia B., additional, Whittaker, Michael R., additional, and Trevaskis, Natalie L., additional

Published
2023
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15. A pH-responsive nanoparticle targets the neurokinin 1 receptor in endosomes to prevent chronic pain

Author

Ramírez-García, Paulina D., Retamal, Jeffri S., Shenoy, Priyank, Imlach, Wendy, Sykes, Matthew, Truong, Nghia, Constandil, Luis, Pelissier, Teresa, Nowell, Cameron J., Khor, Song Y., Layani, Louis M., Lumb, Chris, Poole, Daniel P., Lieu, TinaMarie, Stewart, Gregory D., Mai, Quynh N., Jensen, Dane D., Latorre, Rocco, Scheff, Nicole N., Schmidt, Brian L., Quinn, John F., Whittaker, Michael R., Veldhuis, Nicholas A., Davis, Thomas P., and Bunnett, Nigel W.

Published
2019
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16. Utilization of endogenous albumin trafficking pathways in the lungs has potential to modestly increase the lung interstitial access and absorption of drug delivery systems after inhaled administration

Author

Ibrahim, Jibriil P, primary, Butcher, Neville J, additional, Kothapalli, Ashok, additional, Subasic, Christopher N, additional, Blanchfield, Joanne T, additional, Whittaker, Andrew K., additional, Whittaker, Michael R, additional, and Kaminskas, Lisa M, additional

Published
2023
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29. Thiol-responsive lyotropic liquid crystals exhibit triggered phase re-arrangement and hydrogen sulfide (H2S) release

Author

Urquhart, Matthew C., Ercole, Francesca, Clulow, Andrew J., Davis, Thomas P., Whittaker, Michael R., Boyd, Ben J., Quinn, John F., Urquhart, Matthew C., Ercole, Francesca, Clulow, Andrew J., Davis, Thomas P., Whittaker, Michael R., Boyd, Ben J., and Quinn, John F.

Abstract

Hydrogen sulfide (H2S) is an important signalling molecule with potential pharmaceutical applications. In pursuit of a suitable delivery system for H2S, herein we apply an amphiphilic trisulfide to concomitantly alter the mesophase behaviour of dispersed lipid particles and enable triggered H2S release. Amperometric release studies indicate the trisulfide acts as a sustained H2S donor, with inclusion into the mesophase attenuating release vs neat dispersed trisulfide. Taken together the results highlight the potential for including trisulfide-based additives in stimuli-responsive drug delivery vehicles.

Published
2022

33. Thiol-Reactive Star Polymers Functionalized with Short Ethoxy-Containing Moieties Exhibit Enhanced Uptake in Acute Lymphoblastic Leukemia Cells

Author

Bayat, Narges, McOrist, Nathan, Ariotti, Nicholas, Lai, May, Sia, Keith CS, Li, Yuhuan, Grace, James L, Quinn, John F, Whittaker, Michael R, Kavallaris, Maria, Davis, Thomas P, and Lock, Richard B

Subjects
Polymers, flow cytometry, leukemia, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Xenograft Model Antitumor Assays, Endocytosis, Polyethylene Glycols, Mice, Drug Delivery Systems, International Journal of Nanomedicine, Cell Line, Tumor, microscopy, Animals, Humans, Nanoparticles, Ethylene Glycols, Sulfhydryl Compounds, targeting, Original Research
Abstract

Narges Bayat,1,2 Nathan McOrist,1 Nicholas Ariotti,3,4 May Lai,5 Keith CS Sia,1,2 Yuhuan Li,5 James L Grace,5 John F Quinn,5 Michael R Whittaker,5 Maria Kavallaris,2,6,7 Thomas P Davis,5,8,9,* Richard B Lock1,2,* 1Leukemia Biology Program, Children’s Cancer Institute, Lowy Cancer Research Centre, University of New South Wales, Sydney, NSW, Australia; 2School of Women’s and Children’s Health, Faculty of Medicine, University of New South Wales, Sydney, Australia; 3Electron Microscope Unit, Mark Wainwright Analytical Centre, Chemical Sciences Building, University of New South Wales, Sydney, NSW, Australia; 4School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia; 5ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, and Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia; 6Tumor Biology and Targeting Program, Children’s Cancer Institute, Lowy Cancer Research Centre, University of New South Wales, Sydney, NSW, Australia; 7Australian Centre for Nanomedicine, ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, University of New South Wales, Sydney, NSW, Australia; 8Department of Chemistry, University of Warwick, Coventry, UK; 9Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St Lucia, QLD 4072, Australia*These authors contributed equally to this workCorrespondence: Richard B LockChildren’s Cancer Institute, Lowy Cancer Research Centre, University of New South Wales, Sydney, PO Box 81, Randwick 2031, NSW, AustraliaTel +61 2 9385 2513Fax +61 2 9662 6583Email rlock@ccia.org.auPurpose: Directing nanoparticles to cancer cells without using antibodies is of great interest. Subtle changes to the surface chemistry of nanoparticles can significantly affect their biological fate, including their propensity to associate with different cell populations. For instance, nanoparticles functionalized with thiol-reactive groups can potentially enhance association with cells that over-express cell-surface thiol groups. The potential of such an approach for enhancing drug delivery for childhood acute lymphoblastic leukemia (ALL) cells has not been investigated. Herein, we investigate the impact of thiol-reactive star polymers on the cellular association and the mechanisms of uptake of the nanoparticles.Methods: We prepared fluorescently labeled star polymers functionalized with an mPEG brush corona and pyridyl disulfide to examine how reactivity to exofacial thiols impacts cellular association with ALL cells. We also studied how variations to the mPEG brush composition could potentially be used as a secondary method for controlling the extent of cell association. Specifically, we examined how the inclusion of shorter diethylene glycol brush moieties into the nanoparticle corona could be used to further influence cell association.Results: Star polymers incorporating both thiol-reactive and diethylene glycol brush moieties exhibited the highest cellular association, followed by those functionalized solely with thiol reactive groups compared to control nanoparticles in T and B pediatric ALL patient-derived xenografts harvested from the spleens and bone marrow of immunodeficient mice. Transfection of cells with an early endosomal marker and imaging with correlative light and electron microscopy confirmed cellular uptake. Endocytosis inhibitors revealed dynamin-dependent clathrin-mediated endocytosis as the main uptake pathway for all the star polymers.Conclusion: Thiol-reactive star polymers having an mPEG brush corona that includes a proportion of diethylene glycol brush moieties represent a potential strategy for improved leukemia cell delivery.Keywords: nanoparticles, targeting, endocytosis, leukemia, flow cytometry, microscopy

Published
2019

37. Oxytocin in the Male Reproductive Tract; The Therapeutic Potential of Oxytocin-Agonists and-Antagonists

Author

Stadler, Beatrix, Whittaker, Michael R., Exintaris, Betty, and Middendorff, Ralf

Subjects
Male, endocrine system, prostate, lcsh:RC648-665, Prostatic Neoplasms, Review, Genitalia, Male, testis, oxytocin receptor signaling, lcsh:Diseases of the endocrine glands. Clinical endocrinology, oxytocin and arginine vasopressin crosstalk, Arginine Vasopressin, Endocrinology, Hormone Antagonists, Receptors, Oxytocin, oxytocin, Animals, Humans, male reproduction, epididymis, hormones, hormone substitutes, and hormone antagonists, Signal Transduction, oxytocin-agonist and antagonist
Abstract

In this review, the role of oxytocin and oxytocin-like agents (acting via the oxytocin receptor and belonging to the oxytocin-family) in the male reproductive tract is considered. Previous research (dating back over 60 years) is revised and connected with recently found aspects of the role oxytocin plays in male reproductive health. The local expression of oxytocin and its receptor in the male reproductive tract of different species is summarized. Colocalization and possible crosstalk to other agents and receptors and their resulting effects are discussed. The role of the newly reported oxytocin focused signaling pathways in the male reproductive tract, other than mediating contractility, is critically examined. The structure and effect of the most promising oxytocin-agonists and -antagonists are reviewed for their potential in treating male disorders with origins in the male reproductive tract such as prostate diseases and ejaculatory disorders.

Published
2020
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38. Lymphatic targeting by albumin-hitchhiking:Applications and optimisation

Author

Abdallah, Mohammad, Muellertz, Olivia O., Styles, Ian K., Moersdorf, Alexander, Quinn, John F., Whittaker, Michael R., Trevaskis, Natalie L., Abdallah, Mohammad, Muellertz, Olivia O., Styles, Ian K., Moersdorf, Alexander, Quinn, John F., Whittaker, Michael R., and Trevaskis, Natalie L.

Abstract

The lymphatic system plays an integral role in the development and progression of a range of disease conditions, which has impelled medical researchers and clinicians to design, develop and utilize advanced lymphatic drug delivery systems. Following interstitial administration, most therapeutics and molecules are cleared from tissues via the draining blood capillaries. Macromolecules and delivery systems > 20 kDa in size or 10-100 nm in diameter are, however, transported from the interstitium via draining lymphatic vessels as they are too large to cross the blood capillary endothelium. Lymphatic uptake of small molecules can be promoted by two general approaches: administration in association with synthetic macromolecular constructs, or through hitchhiking on endogenous cells or macromolecular carriers that are transported from tissues via the lymphatics. In this paper we review the latter approach where molecules are targeted to lymph by hitchhiking on endogenous albumin transport pathways after subcutaneous, intramuscular or intradermal injection. We describe the properties of the lymphatic system and albumin that are relevant to lymphatic targeting, the characteristics of drugs and delivery systems designed to hitchhike on albumin trafficking pathways and how to further optimise these properties, and finally the current applications and potential future directions for albumin-hitchhiking approaches to target the lymphatics.

Published
2020

43. Sulfoxide‐Containing Polymer‐Coated Nanoparticles Demonstrate Minimal Protein Fouling and Improved Blood Circulation

Author

Qiao, Ruirui, primary, Fu, Changkui, additional, Li, Yuhuan, additional, Qi, Xiaole, additional, Ni, Dalong, additional, Nandakumar, Aparna, additional, Siddiqui, Ghizal, additional, Wang, Haiyan, additional, Zhang, Zheng, additional, Wu, Tingting, additional, Zhong, Jian, additional, Tang, Shi‐Yang, additional, Pan, Shuaijun, additional, Zhang, Cheng, additional, Whittaker, Michael R., additional, Engle, Jonathan W., additional, Creek, Darren J., additional, Caruso, Frank, additional, Ke, Pu Chun, additional, Cai, Weibo, additional, Whittaker, Andrew K., additional, and Davis, Thomas P., additional

Published
2020
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48. Delivery of polymeric nanostars for molecular imaging and endoradiotherapy through the enhanced permeability and retention (EPR) effect

Author

Goos, Jeroen A.C.M., primary, Cho, Andrew, additional, Carter, Lukas M., additional, Dilling, Thomas R., additional, Davydova, Maria, additional, Mandleywala, Komal, additional, Puttick, Simon, additional, Gupta, Abhishek, additional, Price, William S., additional, Quinn, John F., additional, Whittaker, Michael R., additional, Lewis, Jason S., additional, and Davis, Thomas P., additional

Published
2020
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50. Thiol-Reactive Star Polymers Functionalized with Short Ethoxy-Containing Moieties Exhibit Enhanced Uptake in Acute Lymphoblastic Leukemia Cells

Author

Bayat,Narges, McOrist,Nathan, Ariotti,Nicholas, Lai,May, Sia,Keith CS, Li,Yuhuan, Grace,James L, Quinn,John F, Whittaker,Michael R, Kavallaris,Maria, Davis,Thomas P, Lock,Richard B, Bayat,Narges, McOrist,Nathan, Ariotti,Nicholas, Lai,May, Sia,Keith CS, Li,Yuhuan, Grace,James L, Quinn,John F, Whittaker,Michael R, Kavallaris,Maria, Davis,Thomas P, and Lock,Richard B

Abstract

Narges Bayat,1,2 Nathan McOrist,1 Nicholas Ariotti,3,4 May Lai,5 Keith CS Sia,1,2 Yuhuan Li,5 James L Grace,5 John F Quinn,5 Michael R Whittaker,5 Maria Kavallaris,2,6,7 Thomas P Davis,5,8,9,* Richard B Lock1,2,* 1Leukemia Biology Program, Children’s Cancer Institute, Lowy Cancer Research Centre, University of New South Wales, Sydney, NSW, Australia; 2School of Women’s and Children’s Health, Faculty of Medicine, University of New South Wales, Sydney, Australia; 3Electron Microscope Unit, Mark Wainwright Analytical Centre, Chemical Sciences Building, University of New South Wales, Sydney, NSW, Australia; 4School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia; 5ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, and Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia; 6Tumor Biology and Targeting Program, Children’s Cancer Institute, Lowy Cancer Research Centre, University of New South Wales, Sydney, NSW, Australia; 7Australian Centre for Nanomedicine, ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, University of New South Wales, Sydney, NSW, Australia; 8Department of Chemistry, University of Warwick, Coventry, UK; 9Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St Lucia, QLD 4072, Australia*These authors contributed equally to this workCorrespondence: Richard B LockChildren’s Cancer Institute, Lowy Cancer Research Centre, University of New South Wales, Sydney, PO Box 81, Randwick 2031, NSW, AustraliaTel +61 2 9385 2513Fax +61 2 9662 6583Email rlock@ccia.org.auPurpose: Directing nanoparticles to cancer cells without using antibodies is of great interest. Subtle changes to the surface chemistry of nanoparticles can significantly affect their biological fate, including their propensity to associate with different cell populations.

Published
2019

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