Fate of Lipid and Encapsulated Drug after Intramuscular Administration of Liposomes Prepared by the Freeze-Thawing Method in Rats

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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) method were also tested for comparison. The inulin-encapsulating efficiencies (EN%) 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 disappearance 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 nodes 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.