MAGNETIC TARGETING OF THERMOSENSITIVE MAGNETOLIPOSOMES TO MOUSE LIVERS IN AN IN-SITU ONLINE PERFUSION SYSTEM

We recently reported the preparation and in vitro targeting of dextran magnetite (DM)-incorporated thermosensitive liposomes, namely thermos ensitive magneto-liposomes (TMs) [Viroonchatapan et al., Pharm. Res. 1 2 1176-1183 (1995)]. The current study was designed to determine wheth er these novel liposomes can be targeted to the mouse liver with the a id of an extracorporeal magnet. An on-line liver perfusion system cons isting primarily of a sample injector, permanent magnets, and a fluore scence detector was established for a real-time measurement of targeti ng efficiency of TMs containing calcein as a fluorescent marker. Norma l and reticuloendothelial system (RES)-blocked livers from mice were u sed for the perfusion experiments. In the RES-blocked livers, percenta ge holdings of TMs were 73-80% and 26-45% in the presence and absence of magnetic field, respectively, indicating an efficient targeting of TMs with a targeting advantage index (TAI) of 1.6-3.1. On the other ha nd, TAI in the normal livers was found to be 1.1-1.4 and less than tha t in the RES-blocked livers, suggesting a role of RES uptake of TMs. T he effects of DM concentrations in TM suspensions on the percentage ho lding of TMs were shown to be minor. Liposome concentration dependence was observed for hepatic uptake of TMs, possibly because of the satur ation of phagocytosis by Kupffer cells. The present results suggest th at TMs would be useful in future cancer treatment by magnetic targetin g combined with drug release in response to hyperthermia.