mp049957p_si_001.pdf (114.57 kB)
Reduction of Drug Toxicity Using Dendrimers Based on Melamine
journal contribution
posted on 2004-09-13, 00:00 authored by Michael F. Neerman, Hui-Ting Chen, Alan R. Parrish, Eric E. SimanekDendrimers based on melamine can reduce the
organ toxicity of solubilized cancer drugs administered by
intraperitoneal injection. Methotrexate and 6-mercaptopurine, both FDA approved anticancer drugs, are known
hepatotoxins. The solubility of these molecules can be
increased by mixing them with a dendrimer based on
melamine. C3H mice were administered subchronic doses
of methotrexate or 6-mercaptopurine with and without a
solubilizing dendrimer. Forty-eight hours after dosing, the
mice were sacrificed and serum was collected for biochemical analyses. The levels of alanine transaminase,
ALT, were used to probe liver damage. When the drugs
are encapsulated by the dendrimer, a significant reduction
in hepatotoxicity is observed: ALT levels from the rescued
groups (drug + dendrimer) were 27% (methotrexate) and
36% (6-mercaptopurine) lower than those of animals
treated with the drug alone.
Keywords: Drug delivery; toxicity; dendrimer; melamine;
methotrexate; 6-mercaptopurine