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1. Design of drug carriers using dendrimers

  1-1. Design of functional dendrimers for drug delivery

Dendrimers are characteristic synthetic polymers whose molecular weight and structure can be controlled. We have designed functional dendrimers that can be used in drug delivery systems (DDS).

Since drug carriers must be biocompatible, we prepared dendrimers modified with polyethylene glycol (PEG), a biocompatible polymer with stealth properties. We found that these dendrimers could encapsulate anticancer drugs and photosensitizers (Fig. 3). We synthesized dendrimers carrying hydrophobic amino acids or cysteine to improve the complex stability and provide controlled release properties. In addition, we synthesized PEG-attached dendrimers conjugating anticancer drugs (Fig. 4). These dendrimers had glutamic acid (Glu) and PEG chains at every terminal. The side chain of Glu was conjugated to an anticancer drug, adriamycin, via an amide bond and a hydrazone bond. Since hydrazone linkage is degraded at a low pH, the drug-conjugated dendrimer via the hydrazone bond exhibited a more efficient drug action than that via the amide bond.

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  • Kojima et al, Bioconjugate Chem., 11, 910 (2000).
  • Kojima et al, Macromolecules, 36, 2183 (2003).
  • Kojima et al, Bioconjugate Chem., 19, 2280 (2008).
  • Kono et al, Polymer, 49, 2832 (2008).
  • Kono et al, Biomaterials, 29, 1664 (2008).

  

Encapsulation of various materials in the PEGylated dendrimers

Figure 3. Encapsulation of various materials in the PEGylated dendrimers.

  

pH-Dependent release of drug from PEGylated dendrimers

Figure 4. pH-Dependent release of drug from PEGylated dendrimers.

  

  1-2. Visualization and biodistribution of these dendrimers

PEG is known to not only be biocompatible but also to inhibit nonspecific interactions with biomolecules. Many researchers have reported that PEG can strongly enhance the bioavailability of various drug carriers. We visualized PEG-attached dendrimers and analyzed their biodistribution.

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  • Kojima et al, Nanomedicine, 7, 1001 (2011).
  • Kojima et al, Int. J. Pharm., 383, 293 (2010).