Abstract
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.
Original language | English |
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Pages (from-to) | 93-103 |
Number of pages | 11 |
Journal | Macromolecular Bioscience |
Volume | 12 |
Issue number | 1 |
DOIs | |
Publication status | Published - 1 Jan 2012 |
Keywords
- Dendrimers
- Drug delivery systems
- Kidney
- Platinum linkers
- Sunitinib