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Instruments / Technical Area	Publication Details	Published
B21-High Throughput SAXS	Long acting injectables for therapeutic proteins Sally Ryan , Kim Shortall , Michele Dully , Ahmed Djehedar , David Murray , James Butler , John Neilan , Tewfik Soulimane , Sarah P. Hudson Colloids And Surfaces B: Biointerfaces 8 DOI: 10.1016/j.colsurfb.2022.112644 Open Access Show Abstract ▼ Abstract: Biotherapeutic development presents a myriad of challenges in relation to delivery, in particular for protein therapeutics. Protein delivery is complicated due to hydrophilicity, size, rate of degradation in vivo, low permeation through biological barriers, pH and temperature sensitivity, as well as the need to conserve its quaternary structure to retain function. To preserve therapeutic levels in vivo, proteins require frequent administration due to their short half-lives. Formulation strategies combining proteins with lipid carriers for parenteral administration show potential for improving bioavailability, while preserving protein activity and bypassing the mucosal barriers of the body. Encapsulating protein in long acting injectable delivery systems can improve therapeutic indices by prolonging and controlling protein release and reducing the need for repeat interventions. Two lyotropic crystal forming lipids, monoolein and phytantriol, have been formulated to produce lipidic cubic phases and assessed for their use as long acting protein eluting injectables. Three soluble proteins, cytochrome c, glyceraldehyde-3-phosphate dehydrogenase and aldehyde dehydrogenase and one membrane protein, cytochrome c oxidase, were incorporated into bulk cubic phase formulations of each lipid system to comparatively assess protein release kinetics. The activity of the soluble proteins was measured upon release from a phytantriol bulk cubic phase and phytantriol cubosomes, produced using a liquid precursor method.	Jun 2022
I08-Scanning X-ray Microscopy beamline (SXM)	Synchrotron-based X-ray fluorescence study of gold nanorods and skin elements distribution into excised human skin layers Nouf N. Mahmoud , Messaoud Harfouche , Alaaldin M. Alkilany , Amal G. Al-Bakri , Rania A. El-Qirem , Sawsan A. Shraim , Enam A. Khalil Colloids And Surfaces B: Biointerfaces DOI: 10.1016/j.colsurfb.2018.02.021 Diamond Proposal Number(s): [15994] Show Abstract ▼ Abstract: Understanding the distribution of nanoparticles in skin layers is fundamentally important and essential for developing nanoparticle-based dermal drug delivery systems. In the present study, we provide insights into the distribution of gold nanorods (GNRs) functionalized with hydrophobic or hydrophilic ligands in human skin layers using synchrotron X-ray fluorescence (SR-XRF) spectroscopy, confocal microscopy, and transmission electron microscopy. The results confirmed the important role that the surface chemistry of GNRs plays in their penetration into the skin; the GNRs coated with polyethylene glycol were distributed into the skin layers to a greater extent than the GNRs coated with hydrophobic polystyrene thiol. In addition, SR-XRF analysis revealed that the spatial distribution of endogenous elements (phosphorus and sulfur) in skin layers demonstrated a significant “anti-correlation” relationship with that of GNRs. These results suggest possible association (via adsorption) between the GNRs and these two elements localized in skin, which can be valuable for understanding the penetration mechanism of gold nanoparticles into the skin.	Feb 2018
I07-Surface & interface diffraction	The influence of hyaluronan on the structure of a DPPC-bilayer under high pressures Thomas Zander , D. C. Florian Wieland , Akanksha Raj , Min Wang , Benedikt Nowak , Christina Krywka , Andra Dėdinaitė , Per Martin Claesson , Vasil M. Garamus , Andreas Schreyer , Regine Willumeit-Römer Colloids And Surfaces B: Biointerfaces 142, 230–238 DOI: 10.1016/j.colsurfb.2016.02.040 Diamond Proposal Number(s): [9856] Show Abstract ▼ Abstract: The superior lubrication properties of synovial joints have inspired many studies aiming at uncovering the molecular mechanisms which give rise to low friction and wear. However, the mechanisms are not fully understood yet, and, in particular, it has not been elucidated how the biolubricants present at the interface of cartilage respond to high pressures, which arise during high loads of joints. In this study we utilize a simple model system composed of two biomolecules that have been implied as being important for joint lubrication. It consists of a solid supported dipalmitoylphosphatidylcholin (DPPC) bilayer, which was formed via vesicles fusion on a flat Si wafer, and the anionic polysaccharide hyaluronan (HA). We first characterized the structure of the HA layer that adsorbed to the DPPC bilayers at ambient pressure and different temperatures using X-ray reflectivity (XRR) measurements. Next, XRR was utilized to evaluate the response of the system to high hydrostatic pressures, up to 2 kbar (200 MPa), at three different temperatures. By means of fluorescence microscopy images the distribution of DPPC and HA on the surface was visualized. Our data suggest that HA adsorbs to the headgroup region that is oriented towards the water side of the supported bilayer. Phase transitions of the bilayer in response to temperature and pressure changes were also observed in presence and absence of HA. Our results reveal a higher stability against high hydrostatic pressures for DPPC/HA composite layers compared to that of the DPPC bilayer in absence of HA.	Jun 2016
B21-High Throughput SAXS	A self-assembling fluorescent dipeptide conjugate for cell labelling Steven Kirkham , Ian W. Hamley , Andrew M. Smith , Ricardo M. Gouveia , Che J. Connon , Mehedi Reza , Janne Ruokolainen Colloids And Surfaces B: Biointerfaces 137, 104 - 108 DOI: 10.1016/j.colsurfb.2015.04.062 Diamond Proposal Number(s): [10007] Open Access Show Abstract ▼ Abstract: Derivatives of fluorophore FITC (fluorescein isothiocyanate) are widely used in bioassays to label proteins and cells. An N-terminal leucine dipeptide is attached to FITC, and we show that this simple conjugate molecule is cytocompatible and is uptaken by cells (human dermal and corneal fibroblasts) in contrast to FITC itself. Co-localisation shows that FITC-LL segregates in peri-nuclear and intracellular vesicle regions. Above a critical aggregation concentration, the conjugate is shown to self-assemble into beta-sheet nanostructures comprising molecular bilayers.	Jan 2016

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