Chemotherapy with hybrid liposomes and application to drug delivery system with hybrid liposomes

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We have produced hybrid liposomes (HL) which can be prepared by sonication of vesicular and micellar molecules in a buffer solution. The physical properties of HL such as size, shape, membrane fluidity, and the temperature of phase separation can be controlled by changing the constituents and compositional ratio. We have employed HL for the research of cancers and interesting results are as follows;(A) The uniform and stable structure of HL composed of dimyristoylphosphatidylcholine (DMPC) and polyoxyethylene (23)-dodecyl ether (C12 (E0) 2) with a diameter of 80 nm was revealed on the basis of electron microscopy and dynamic light scattering measurements.(B) The remarkable inhibitory effects of HL on the growth of human-B-lymphoma (RAJI) cells were attained. Induction of apoptosis by HL was obtained using flow cytometry, DNA agarose gel electrophoresis, micrograph with TUNEL method and time-laps video.(C) Significantly prolonged survival and remarkable reduction of tumor volume were obtained using mice model of carcinoma after the treatment with HL without any drug.(D) There were no abnormal findings on blood test, hemato chemistry, relative organ weight and autopsy of normal rats after administering HL on the basis of chronic toxicity tests.(E) In clinical applications, prolonged survival was attained in patients with lymphoma after the intravenous injection of HL without any side effect and remarkable reduction of neoplasm was obtained after the local administration of hybrid liposomes.(F) Remarkable immunostimulation effects of HL on human peripheral blood mononuclear cells were obtained in vitro.(G) A novel approach of gentamicin therapy for Duchenne Muscular Dystrophy using HL was examined. Mdx mice treated with gentamicin encapsulated HL did not show toxicity and the efficiency of dystrophin positive fibers in the mdx mice injected with gentamicin encapsulated HL was obtained.