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fbtwitterlinkedinvimeoflicker grey 14rssslideshare1
Aljayyoussi, Ghaith
Languages: English
Types: Doctoral thesis
Subjects: RM
The ultimate aim of the work described in this thesis was to (1) utilise PAMAM dendrimers as a tool to achieve differential transport across the intestinal mucosa and the blood brain barrier, where these dendrimers can be used to\ud achieve oral bioavailability but avoid BBB penetration and CNS access and (2) to create cannabinoid-dendrimer conjugates that are active in their own right\ud and whose penetration to the brain is prevented but whose intestinal activity is afforded for the treatment of IBD.\ud Overall, the work described in this thesis has promoted a strategy whereby an active polymer (dendrimer)-drug conjugate could be formed that is active in its\ud own right and where the polymer can serve to provide differential biological barrier transport which with regard to cannabinoid pharmacology obviates adverse CNS effects.\ud The work in this thesis describes the design and synthesis of novel and active cannabinoid structures that should have commercial interest. These novel compounds served to further elucidate SAR in amino alkyl indole cannabinoids.\ud SAR findings have revealed a site on these cannabinoids that can be functionally altered without loss of pharmacological activity.\ud Additionally, studies in this thesis have led to the development of a novel radiolabelling strategy for anionic polymers that offers a number of distinct advantages over other approaches.\ud Ultimately, a novel stable Dendrimer-cannabinoid conjugate has been synthesised but to date has not shown biological activity in the models utilised in this work.
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    • Newkome, G.R., et al., Dendritic Molecules: Concepts, Syntheses, Perspectives 1996: WILEY-VCH. 262.
    • Patri, A.K., I.J. Majoros, and J.R. Baker, Dendritic polymer macromolecular carriers for drug delivery. Curr Opin Chem Biol, 2002.
    • 6(4): p. 466-71.
    • Journal of Chemical Technology & Biotechnology, 2001. 76(9): p. 903- 918.
    • Buhleier, E., W. Wehner, and F. Vögtle, 'Cascade'- and 'Non skid-Chainlike' syntheses of molecular cavity topologies. Synthesis, 1978: p. 155- 158.
    • Tomalia, D.A., et al., A New Class of Polymers: Starburt-Dendritic Macromolecules. Polym. J., 1985. 17: p. 117.
    • Kim, Y. and S.C. Zimmerman, Applications of dendrimers in bio-organic chemistry. Curr Opin Chem Biol, 1998. 2(6): p. 733-42.
    • Frechet, J., Functional polymers and dendrimers: reactivity, molecular architecture, and interfacial energy. Science, 1994. 263(5154): p. 1710- 1715.
    • Boas, U. and P.M. Heegaard, Dendrimers in drug research. Chem Soc Rev, 2004. 33(1): p. 43-63.
    • Tomalia, D.A., A.M. Naylor, and W.A. Goddard, Starburst Dendrimers: Molecular-Level Control of Size, Shape, Surface Chemistry, Topology, and Flexibility from Atoms to Macroscopic Matter. Angewandte Chemie International Edition in English, 1990. 29(2): p. 138-175.
    • Hodge, P., Polymer science branches out. Nature, 1993. 362(6415): p.
    • Hawker, C.J. and J.M.J. Frechet, Preparation of polymers with controlled molecular architecture. A new convergent approach to dendritic macromolecules. Journal of the American Chemical Society, 1990.
    • 112(21): p. 7638-7647.
    • Esfand, R. and D.A. Tomalia, Poly(amidoamine) (PAMAM) dendrimers: from biomimicry to drug delivery and biomedical applications. Drug Discov Today, 2001. 6(8): p. 427-436.
    • Caminati, G., N.J. Turro, and D.A. Tomalia, Photophysical investigation of starburst dendrimers and their interactions with anionic and cationic surfactants. Journal of the American Chemical Society, 1990. 112(23): p.
    • 150. Ohno, K., K.D. Pettigrew, and S.I. Rapoport, Lower limits of cerebrovascular permeability to nonelectrolytes in the conscious rat. American Journal of Physiology - Heart and Circulatory Physiology, 1978. 235(3): p. H299-H307.
    • 151. Artursson, P. and J. Karlsson, Correlation between oral drug absorption in humans and apparent drug permeability coefficients in human intestinal epithelial (Caco-2) cells. Biochemical and Biophysical Research Communications, 1991. 175(3): p. 880-885.
    • 152. Yamashita, S., et al., Analysis of Drug Permeation Across Caco-2 Monolayer: Implication for Predicting In Vivo Drug Absorption. Pharmaceutical Research, 1997. 14(4): p. 486-491.
    • 153. Lennernäs, H., Human intestinal permeability. Journal of Pharmaceutical Sciences, 1998. 87(4): p. 403-410.
    • 154. Misfeldt, D.S., S.T. Hamamoto, and D.R. Pitelka, Transepithelial transport in cell culture. Proc Natl Acad Sci U S A, 1976. 73(4): p. 1212-6.
    • 155. Cho, M.J., et al., The Madin Darby canine kidney (MDCK) epithelial cell monolayer as a model cellular transport barrier. Pharm Res, 1989. 6(1): p. 71-7.
    • 156. Irvine, J.D., et al., MDCK (Madin-Darby canine kidney) cells: A tool for membrane permeability screening. J Pharm Sci, 1999. 88(1): p. 28-33.
    • 157. Gumbleton, M. and K.L. Audus, Progress and limitations in the use of in vitro cell cultures to serve as a permeability screen for the blood-brain barrier. J Pharm Sci, 2001. 90(11): p. 1681-98.
    • 158. Cummins, C.L., et al., In vivo modulation of intestinal CYP3A metabolism by P-glycoprotein: studies using the rat single-pass intestinal perfusion model. J Pharmacol Exp Ther, 2003. 305(1): p. 306-14.
    • 159. Bjarnason, I., A. MacPherson, and D. Hollander, Intestinal permeability: an overview. Gastroenterology, 1995. 108(5): p. 1566-81.
    • 160. Kitchens, K., et al., Transport of Poly(Amidoamine) Dendrimers across Caco-2 Cell Monolayers: Influence of Size, Charge and Fluorescent Labeling. Pharmaceutical Research, 2006. 23(12): p. 2818-2826.
    • 161. Jevprasesphant, R., et al., Engineering of Dendrimer Surfaces to Enhance Transepithelial Transport and Reduce Cytotoxicity. Pharmaceutical Research, 2003. 20(10): p. 1543-1550.
    • 162. D'Emanuele, A., et al., The use of a dendrimer-propranolol prodrug to bypass efflux transporters and enhance oral bioavailability. Journal of Controlled Release, 2004. 95(3): p. 447-453.
    • 163. Najlah, M., et al., Synthesis and Assessment of First-Generation Polyamidoamine Dendrimer Prodrugs to Enhance the Cellular Permeability of P-gp Substrates. Bioconjugate Chemistry, 2007. 18(3): p. 937-946.
    • 164. Ke, W., et al., Enhanced oral bioavailability of doxorubicin in a dendrimer drug delivery system. Journal of Pharmaceutical Sciences, 2008. 97(6): p. 2208-2216.
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