Macromolecular Bioscience · 2011 · 22 citations · 29 references
PharmacyPharmaceuticsPharmacologyDrug DeliveryNanoparticle Drug DeliveryTargeted Drug DeliveryNanomaterials For Drug DeliveryNanoparticle DesignRenal DiseaseRenal PharmacologyTargeting LigandsTyrosine Kinase InhibitorsDendrimer Drug DeliveryNanoparticle DeliveryRenal DrugsRenal TargetingTargeted Molecular TherapyTargeting Ligand ConjugationTyrosine Kinase Inhibitor Therapy
The development of a macromolecular conjugate of a multitargeted tyrosine kinase inhibitor is described that can be used for renal-specific delivery into proximal tubular cells. A novel sunitinib analogue, that is, 17864, is conjugated to a NH(2) -PAMAM-G3 dendrimer via the platinum (II)-based Universal Linkage System (ULS™). The activity of 17864 is retained after coordination to the ULS linker alone or when coupled to NH(2) -PAMAM-G3. 17864-UlS-NH(2) -PAMAM-G3 is non-toxic to proximal tubular cells in vitro. After intravenous administration to mice, 17864-UlS-NH(2) -PAMAM-G3 rapidly and efficiently accumulates in the kidneys. These results are encouraging for future studies focusing on the development of novel therapeutics for the treatment of renal diseases.
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