Fate of lipid and encapsulated drug after intramuscular administration of liposomes prepared by the freeze-thawing method in rats.

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Abstract
In order to assess the utility of liposomes prepared by the freeze-thawing (FT) method as a drug carrier, the fate of the liposomes themselves and of encapsulated drug following intramuscular administration was investigated in rats. Liposomes were prepared from yolk phospholipid, and 3H-labeled dipalmitoyl-phosphatidylcholine (3H-DPPC) and 14C-labeled inulin were employed as markers of the lipid and the drug, respectively. Liposomes prepared by the ordinary hydration (HY) methods were also tested for comparison. The inulin-encapsulating efficiencies (EV%) of liposomes prepared by the FT, HY with buffer, and HY with distilled water methods were 60%, 4%, and 45%, respectively. At 24 h after intramuscular injection of liposomes about half of the injected 3H-DPPC still remained in the injection site regardless of the preparation method. A considerable amount of 3H-DPPC was detected in the regional lymph nodes, suggesting a significant contribution of the lymphatic route in the absorption of liposomes. On the other hand, the disapperance of 14C-inulin from the muscle varied with EN%, and liposomes prepared by the FT method showed higher retention than those prepared by the HY method. The difference in absorption was well reflected in the plasma concentration and urinary recovery of 14C-inulin. Accumulation of 14C-inulin in the lymph node was also observed. The concentration ratios of 14C-inulin to 3H-DPPC in the muscle and lymph nodes increased with time, indicating that the lipid was absorbed faster than 14C-inulin. Liposomes prepared by the FT method were concluded to be effective in retarding the absorption and enhancing the lymphatic delivery of the drug, giving high EN% by a simple procedure.