Carbamylation decreases the cytotoxicity but not the drug-carrier properties of polylysines.
The charge density of Poly(D-lysine) was reduced by the carbamylation of the lysyl residues with potassium cyanate. A decrease in the charge density of poly(D-lysine) by 25% and 50% reduced the cytotoxicity of the ligand to cultured L929 cells by a 5-, and a 20 to 25-fold level, respectively, as estimated by using either the viability or the protein assay. The uptake of cyanate-modified poly(D-lysine) ligands in cultured L929 cells was not reduced, while the uptake of poly(D-lysine)/Heparin complex was reduced by 80%, as compared to that of unmodified poly(D-lysine). The in vivo biodistribution of cyanate-modified poly(D-lysine) ligands in the lungs and the liver of mice was not altered in comparison to that of unmodified poly(D-lysine), whereas the poly(D-lysine)/Heparin complex was only accumulated in the liver but not in the lungs. The data in this paper indicate that a 50% decrease in the positive charge density of poly(D-lysine) reduces the toxicity, but not the carrier potential of this polycationic ligand.
Ekrami
H M
HM
Department of Pharmaceutical Sciences, University of Southern California School of Pharmacy, Los Angeles 90033, USA.
Shen
W C
WC
D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003485:Cyanates / Q000737:chemistry*; D004337:Drug Carriers; D016503:Drug Delivery Systems; D007457:Iodine Radioisotopes; D007668:Kidney / Q000378:metabolism; D008024:Ligands; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D051379:Mice; D008970:Molecular Weight; D011107:Polylysine / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity*; D011506:Proteins / Q000378:metabolism; D014018:Tissue Distribution
D003485:Cyanates; D004337:Drug Carriers; D007457:Iodine Radioisotopes; D008024:Ligands; D011506:Proteins; D011107:Polylysine; C024835:potassium cyanate