Carrier-mediated delivery improves the efficacy of 9-(2-phosphonylmethoxyethyl)adenine against hepatitis B virus.

We recently synthesized a lipophilic prodrug of 9-(2-phosphonyl-methoxyethyl)adenine (PMEA), designated PMEA-LO, and incorporated it into reconstituted lactosylated high-density lipoprotein (LacNeoHDL). In a rat model, LacNeoHDL-associated PMEA-LO was internalized by the asialoglycoprotein receptor on parenchymal liver cells and converted into its active diphosphorylated metabolite. To further evaluate the therapeutic potential of the carrier-associated prodrug, we examined in this study the processing of (125)I-labeled PMEA-LO--loaded LacNeoHDL by HepG2 cells.