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New Material for Delivery System: The Guerbet Glycosides

New Material for Delivery System: The Guerbet Glycosides. Membrane Biophysics:Theory and Experiment Kavli Institute of Theoretical Physics, CAS, China 7 th May 2012 – 1 st June 2012. Rauzah Hashim Chemistry Department University of Malaya 50603 Kuala Lumpur. Zhoukoudian Peking Man.

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New Material for Delivery System: The Guerbet Glycosides

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  1. New Material for Delivery System: The Guerbet Glycosides

    Membrane Biophysics:Theory and Experiment Kavli Institute of Theoretical Physics, CAS, China 7th May 2012 – 1st June 2012 RauzahHashim Chemistry Department University of Malaya 50603 Kuala Lumpur Zhoukoudian Peking Man
  2. 你吃了吗？ Have you eaten?
  3. Acknowledgement Kavli Institute of Theoretical Physics China Chinese Academy of Science Professor Ou-Yang Zhong-Can Professor ZhangchunTu Dr. CiZhuang Staff of KITPC
  4. My Presentation Plan Guerbet Glycoside as Nature-likeGlycolipid Using Guerbet Glycoside as Delivery System
  5. Guerbet Glycosides as Nature-likeGlycolipids R. Hashim, et al. 2012 Liquid Crystals,39 (1), 1-17  Brooks, et al, 2011, Liquid Crystals, 38(11 12), 1725 1734 N. I. M. Zahid  et al. 2012, to be submitted University of Malaya Dr. T. Heidelberg Dr. R. S. D. Hussen S. M. Mirzadeh N. I. M. Zahid KhairulAmani AIST Prof. H. Minamikawa Osaka Sangyo University Prof. A. Sugimura Imperial College Prof. J.M. Seddon Dr. N. Brook Dr. C. Conn (CSIRO) KITPC 2012 Beijing
  6. Motivation Glycolipid as cell membrane material Strengthen the cell wall Assists in cell processes, for example Exo-/endocytosis Cell recognition Cell transport Understand factors controlling them through liquid crystal science http://cellbiology.med.unsw.edu.au/units/images/Cell_membrane.png KITPC 2012 Beijing
  7. Structural Diversity Sphingolipids Glycosylphosphopolyprenols Glyco-glycerolipid Alkyl-Polyglucosides APGs Lipids, 2004. 39(10): p. 933-53 Nonionic Surfactants: Alkyl Polyglucosides. Surfactant Science Series. Vol. 91 2000,  Current Opinion in Colloid and Interface Science. 2002, 7: 395-409 KITPC 2012 Beijing Dembitsky, V.M., Lipids, 2004. 39(10): p. 933-53
  8. Lessons from Nature… Membrane functions relate to sugar lipids Membrane stability Delivery process Exo-/endocytosis Cell membrane self-assembly relates to LC Liquid Crystals, 2012, 39, 1-17 (invited article) KITPC 2012 Beijing
  9. Liquid Crystals Phases Liquid Crystals, 2012, 39, 1-17 ChemPhys Lipids, 2000. 104(1): p. 75-91 ChemPhys Lipids, 2007. 148(1): p. 26-50 KITPC 2012 Beijing
  10. Synthetic Glycolipids 1, 2- dialkyl/diacyl-glycerol glycolipids 1,3-glycosyl-glycerol glycolipids Guerbet glycolipids Eg. Biochim Biophys Acta, 2000. 1509(1-2): p. 203-15. Eg. Langmuir, 1997. 13(9): p. 2564-2571. Thin Solid Films, 2006. 509(1-2): p. 27-35 Liquid Crystals, 2012, 39, 1-17 (invited article) KITPC 2012 Beijing
  11. Objectives Materials for Delivery Systems To mimic Nature (design approach) Chain branching Derive from natural resources Guerbet alcohols Available commercially Nature-like synthetic alkyl branched chain glycolipids: a review on chemical structure and self-assembly properties, 2011 Invited Article Liquid Crystals,39 (1), 1-17  KITPC 2012 Beijing
  12. Guerbet Sugars From Guerbet alcohols (by Marcel Guerbet 1909) Guerbet alcohols are industrial products 5 chain branching lengths available commercially Lower melting/boiling points than corresponding straight chains alcohols Many commercial patents filed using Guerbet compounds First reported by Nilsson, F., Söderman, O. and Johansson, I. Langmuir, 1997 KITPC 2012 Beijing
  13. Lewis Acid Glycosidation ROH CH2Cl2 Glycosidation Step Deacetylation Step Acetylation Step Ac2 O / H2SO4 0-60oC BF3Et2O rt N2 3-4 hr NaOMe Abs MeOH ROH CH2Cl2 NaOAc/Ac2O SnCl3 Rt N2 -48 hr Thin Solid Films, 2006. 509(1-2): p. 27-35 KITPC 2012 Beijing
  14. Guerbet Glycosides Thin Solid Films, 2006. 509(1-2): p. 27-35 Thermotropic monosacharrides Guerbet glycosides afford many non-lamellar phases Q ? KITPC 2012 Beijing
  15. Guerbet Glycosides Thin Solid Films, 2006. 509(1-2): p. 27-35 Im3m Thermotropic disaccharides Pn3m Ia3d Q ? Q ? Pn3m Solid KITPC 2012 Beijing
  16. Chain Branching Effect Guebert Alcohols Sugar Guebert Sugars Maltose Transition Temperature LC- Iso Glucose Lactose Chain Length Galactose Vill,V. and Hashim, R., 2002. Current Opinion in Colloid & Interface Science, 7(5-6), 395-409. Cellobiose Thin Solid Films, 2006. 509(1-2): p. 27-35
  17. Effect of C-4 epimer Liquid Crystals, 2007. 34(2): p. 251–265. Galactoside Axial C4-OH Increase transition temp, due to increase in intra-hydrogen bonding HO Galactolipid found in plant, esp. photosynthesis cell Glucoside Glucolipid is found mainly in bacteria HO Chem Phys Lipids, 2000. 104(1): p. 75-91 Thin Solid Films, 2006. 509(1-2): p. 27-35
  18. Glycosidic (/) Linkage Important to examine the orientation of anomeric linkage with respect to C4-OH -anomer OR -dodecylmaltoside -dodecylmaltoside -anomer OR , Auvray et al Eur. Phys. J. E 4, 489–504 (2001) Thin Solid Films, 2006. 509(1-2): p. 27-35
  19. Intersugar glycosidic (/) linkage Cellebioside OH Lactoside Extended ribbon Maltoside Flexible helix Kennedy, Carbohydrate Chemistry, Clarendon Press, Oxford, 1988 Thin Solid Films, 2006. 509(1-2): p. 27-35
  20. Epimeric/Anomeric Relationship Carbohydrate Research, 346, (18), 27 December 2011,2948 2956
  21. v/l (in Å2 ) for straight and branched chains Nature-like synthetic alkyl branched chain glycolipids: a review on chemical structure and self-assembly properties, 2011 Invited Article Liquid Crystals,39 (1), 1-17  KITPC 2012 Beijing
  22. QII Phases in Excess Water Infinitely Periodic Minimal Surfaces, IPMS Pn3m, Im3m and Ia3d relevant to biological membrane Hydration packing density : gyroid, G (Ia3d) > diamond, D (Pn3m) > Schwarz primitive, P (Im3m) Schwarz primitive, P (Im3m) gyroid, G (Ia3d) diamond, D (Pn3m) The Journal of Physical Chemistry B, 1998. 102(37): p. 7262-7271 Philos Transact A Math Phys Eng Sci, 2006. 364(1847): p. 2635-55 KITPC 2012 Beijing
  23. LC phases in excess water Pn3m Fd3m Ia3d -Glc-OC10C6 R. Hashim, et al. 2012 Liquid Crystals,39 (1), 1-17  Brooks, et cal, 2011, Liquid Crystals, 38(11 12), 1725 1734  KITPC 2012 Beijing
  24. Conclusions Review self-assembly properties (dry and hydrated) for synthetic branched Guerbet glycosides Guerbet chains give better hydrophobicity Chain branching support non-lamellar curved phases Chain asymmetry leads to denser packing hydration KITPC 2012 Beijing
  25. Physico-chemical Characterization of Branched-chain Glycolipids for Drug Delivery University of Malaya N. Ahmad Dr. H. A. Tajuddin CSIC, Barcelona Prof. C. Solans, Dr. J. Esquena Dr. R. Ramsch Physicochemical Characterization of Natural-like Branched-Chain Glycosides toward Formation of Hexosomes and Vesicles. Langmuir, 2011. 28(5): p. 2395-2403. KITPC 2012 Beijing
  26. Two Guerbet Glycosides Chemical structures of (A) 2-HDG and (B) 2-HDM OPM of the Lawrence experiment for (A) 2-HDG and (B) 2-HDM (L = isotropic phase and HII = inverted hexagonal phase, L = isotropic phase, Lα = lamellar phase, and Sm A = smectic A phase of 2-HDM). Water gradient decreases from left to right. KITPC 2012 Beijing
  27. Pseudo Binary Phase Diagrams (A) 2-HDG and (B) 2-HDM in water as a function of temperature: One-phase region of the isotropic phase (gray) and two-phase region of an inverted hexagonal liquid crystalline phase (A) and lamellar liquid crystalline phase (B) dispersed in water (white). KITPC 2012 Beijing
  28. d-spacing and lattice spacingin dry and hydrated from SAXS Hydrated samples are at 5.0% of surfactants (2- HDG and 2-HDM) KITPC 2012 Beijing
  29. HexosomesFormationfrom 2-HDG Radius distribution of the hexosome dispersion with 0.50 wt % 2-HDG in water obtained by a Contin data analysis of dynamic light scattering results. Corresponding cryo-TEM micrograph of the hexosome dispersion with 0.50 wt % 2-HDG in water. Hexosomes are visible as dark gray, almost spherically shaped particles. KITPC 2012 Beijing
  30. 50 nm VesiclesFormationfrom 2-HDM DLS Cryo-TEM Multi-lamellar vesicle 50 nm Radius distribution of 2-HDM vesicles Cryo-TEM micrograph of a 0.50 wt % 2-HDM dispersion. MLVs (<200nm) with polydisperse nature can be observed. Multi-lamellar vesicles with high polydispersity - unstable KITPC 2012 Beijing
  31. Effect of Adding Anionic Surfactant (AOT) to 2-HDM Vesicles 200 nm. Radius distribution of a 1.0 wt % 2-HDM/AOT dispersion in water. Two main populations were observed at 80 and 25 nm. Cryo-TEM micrograph of a 1.0 wt % 2-HDM/AOT dispersion. Spherical unilamellar vesicles were observed, indicating that AOT induced the formation of small and large unilamellar vesicles. KITPC 2012 Beijing
  32. Effect of Adding Anionic Surfactant (SDS) to 2-HDM Vesicles 200 nm. Radius distribution of a 1.0 wt % 2-HDM/SDS dispersion in water. The main population was observed at 40 nm. Cryo-TEM micrograph of a 1.0 wt % 2-HDM/SDS dispersion. SDS induced the formation of small unilamellar vesicles. The bar represents KITPC 2012 Beijing
  33. Conclusions 2-HDG and 2-HDM are nature-like branched-chain glycolipids with interesting/rich phase behavior. 2-HDG, gives a columnar phase in the dry state, in aqueous forms a hexagonal liquid crystalline dispersion, hexosome 2-HDM, shows a smectic A phase. In water forms a lamellar liquid crystalline dispersion, which leads to the formation of MLVs Additions of AOT and SDS to 2-HDM dispersion induce the formation of unilamellar vesicles, with higher stability. KITPC 2012 Beijing

  34. Fundamental Science of Self-Assembly

    Principal Investigator Prof. Rauzah Hashim Students HairulAmani
  35. COLLABORATIONS Prof. G. Luckhurst Dr. B. A. Timimi Prof. J. M. Seddon Prof. G. Tiddy Dr. Richard Bryce Prof. V. Vill H. Zimmerman Prof. A. Jakli Prof. Ou-YangZhong-Can Dr S. Romano Prof. C. Solans Dr. J. Esquiner Dr. M. Khanpour Prof. H. Takezoe Prof. M. Iwamoto Prof. A. Sugimura Prof.. H. Minamikawa Dr. O. K.Abou-Zied Prof. G. Gurzardyn. AP. Tan Howe Siang Dr. Charlotte Conn KITPC 2012 Beijing
  36. THANK YOU Little Girl from Guizhou KITPC 2012 Beijing
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