Dendrimer biopharmaceutics: toward active dendrimer-cannabinoid drugs

Doctoral thesis English OPEN
Aljayyoussi, Ghaith
  • Subject: 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.
  • References (30)
    30 references, page 1 of 3

    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.

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