A low density lipoprotein-methotrexate covalent complex and its activity against L1210 cells in vitro.

Low-density lipoprotein particles are potential drug carriers, but only lipophilic drug species partition into the core of the system. In this paper the polar drug methotrexate has been coupled to the exterior protein of low density lipoprotein (LDL) particles using the reagent 1-ethyl-3(3'-dimethylaminopropyl) carbodiimide HCl. The coupled system was sized by photon correlation spectroscopy and the in vitro activity of the complex determined against L1210 cells maintained in medium supplemented with fetal calf serum. The reaction between methotrexate and low density lipoprotein is variable but quantifiable, about ten drug molecules being attached to each LDL particle, resulting in an increase in the radius and polydispersity of the particles. The activity of the complex against L1210 murine leukaemia cells has been demonstrated in vitro, but it is 30 times less active than free drug.