Reduction of drug toxicity using dendrimers based on melamine.
Dendrimers 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.
Neerman
Michael F
MF
Department of Chemistry, Texas A&M University, College Station, Texas 77843, USA.
Chen
Hui-Ting
HT
Parrish
Alan R
AR
Simanek
Eric E
EE
D000014:Abnormalities, Drug-Induced / Q000517:prevention & control; D000410:Alanine Transaminase / Q000097:blood / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000633:toxicity; D016503:Drug Delivery Systems; D007274:Injections, Intraperitoneal; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D015122:Mercaptopurine / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000633:toxicity; D008727:Methotrexate / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000633:toxicity; D051379:Mice; D008809:Mice, Inbred C3H; D015394:Molecular Structure; D014227:Triazines / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*
D000970:Antineoplastic Agents; D014227:Triazines; D015122:Mercaptopurine; D000410:Alanine Transaminase; C011907:melamine; D008727:Methotrexate