Specific Hybrid Liposomes with Markedly Enhanced Inhibitory Effects on the Growth of Tumor Cells

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We have produced new-type liposomes, hybrid liposomes, including vesicular and micellar surfactants, whose sizes, phase transition temperature, hydrophobicity and fluidity could be controlled by adding micelles. Recently, the inhibitory effect of hybrid liposomes on the growth of B-lymphoma cells have been obtained in vitro. Furthermore, significantly prolonged survival was attained in rat model of gliomatosis treated with hybrid liposomes including drugs.In this study, we examined the inhibitory effect of hybrid liposomes composed of dimyristoylphosphatidylcholine (DMPC) and poly (oxyethylene) dodecyl ether (C_<12>(EO)_n) on the growth of T-lymphoma cells in vitro.Interestingly, the almost completely inhibitory effects were attained by employing the hybrid liposomes of DMPC/C_<12>(EO)_8 and DMPC/C_<12>(EO)_<12>. This result suggests that the hydrophilic-hydrophobic balance in C_<12>(EO)_n micelles should be of importance for the enhancement of inhibitory effect on the growth of tumor cells. The membrane fluidity of hybrid liposomes on the basis of fluorescence measurements was in harmony with the inhibitory effects.We also examined the morphology of the hybrid liposomes composed of 90mol%DMPC and 10mol% C_<12>(EO)_<12>. It is worthy to note that the clear solutions of the hybrid liposomes having a hydrodynamic diameter of 120-130nm with a single and narrow distribution could be kept over 30 days. The above mentioned results suggest that the uniform and stable hybrid liposomes composed of 90mol% DMPC and 10mol% C_<12>(EO)_<12> should be suitable for clinical chemotherapy.Furthermore, it is of importance that no toxic and side effects to normal rats in vivo were observed in the hybrid liposomes composed of 90mol% DMPC and 10mol% C_<12>(EO)_<12>. Therapeutic experiments are in progress by using rat model.