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Covalent coupling of nucleosides to low density lipoprotein (LDL) generates macrophage specific (drug)-carriers.

Covalent coupling of thymidine and azidothymidine (ZIDOVUDINE) to epsilon-amino groups of lysine side chains of LDL-Apo B is described. This procedure generates LDL-nucleoside particles that exhibits affinity solely for the scavenger receptor pathway on macrophages which is demonstrated by cell culture experiments. Autoradiography shows that 3H-thymidine, as representative of nucleosides, is delivered to the cell nucleus. Hence internalization, lysosomal cleavage and triphosphorylation of thymidine evidently had occurred. The application of this new method of drug targeting is macrophage selective inhibition of HIV-reverse transcriptase in AIDS.