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Dendrimers for drug delivery p1

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  • 1. DENDRIMERS FOR DRUG DELIVERY
  • 2. Dendrimers
    • Tree-like polymers, branching out from a central core and subdividing into hierarchical branching units
    • - Not more that 15 nm in size, Mol. Wt very high
    • - Very dense surface surrounding a relatively hollow core (vs. the linear structure in traditional polymers)
  • 3. Dendrimers
    • The first dendrimers were synthesized by Tomalia and co-workers at Dow Chemical in the early 1980s in parallel with Newkome’s ‘arborol’ systems.
    • In 2008 there were over 10 000 scientific reports and 1000 patents dealing with dendritic structures.
    Courtesy of: http://www.uea.ac.uk/cap/wmcc/anc.htm
  • 4. Dendritic polymers
    • Dendritic materials comprise sub-classes such as
      • dendrimers
      • dendrons
      • hyperbranched polymers
      • dendrigraft polymers
      • dendronized polymers
    • Dendritic polymers exhibit very different properties compared to their linear analogues.
    • Vogtle laboratory in 1978 reported the first concept of branching by repetitive growth
  • 5. Dendritic Family
  • 6. Structural Components of Dendrmers
  • 7. Dendrigraft polymers
    • Dendrigraft polymers, sometimes referred to as arborescent polymers, are a relatively new addition to the dendritic family, combining features of dendrimers and hyperbranched polymers with linear polymers.
    • Dendrigraft polymers are grown in generations, much like dendrimers, but the repeating unit is an oligomer or a polymer chain, rather than a small monomer unit.
    • As dendrigraft polymers flexible polymers with very high molecular weights are obtained rapidly.
    • Examples of dendrigraft polymers are:
      • Comb-bursts
      • arborescent polybutadiene,…
  • 8. Dendronized polymers
    • Dendronized polymers, sometimes termed ‘‘rod-shaped polymers’’, are structures having a linear backbone with dendritic sidechains.
    • Dendronized polymers are a sub-class of comb-polymers where the ‘‘comb’s teeth’’ are dendrons instead of linear polymer chains.
    • Fully stretched out dendronized polymers are rod-like cylindrical polymers (‘‘nanotubes’’) and are believed to have new and interesting properties, since they have dimensions reminiscent of several biological functional units, such as the mosaic virus (lengths up to 400 nm and diameters up to 6 nm).
    • Dendronized polymers have exceptionally high aspect ratio compared to the globular dendrimers, i.e. they are not only molecular objects; they are also form-anisotropic nanoscopic objects.
    • Examples:
      • PAMAM-based dendronized polymers,
      • P(bis-MPA)-based dendronized polymers,
      • Fre´chet-type dendronized polymers,
      • Percec-type dendronized polymers, ...
  • 9. Applications in Pharmaceutical Industry
      • drugs e.g. VivaGel®active SPL7013
      • drug delivery –
      • Small molecules
      • proteins
      • tissue targeting
      • Drug solublization
      • siRNA/DNA delivery
      • diagnostics & materials applications
  • 10. Applications in Drug/Protein Delivery
      • Improved efficacy of drugs
      • Extension of drug half-life
      • Reduced toxicity
      • Active or passive targeting (e.g. EPR*)
      • Product lifecycle management
      • Improved solubility of drugs
      • Drug “rescue”
  • 11. Improved Drug Solubility
    • Utilizing a dendrimer construct the aqueous solubility of the drug Paclitaxel was increased >9,000X.
    Paclitaxel aqueous solubility 0.8 mg/mL
  • 12. Drugs Delivered Through Dendrimers