Membrane Targeted Chemotherapy with Hybrid Liposomes for Tumor Cells Leading to Apoptosis

Ryuichi      Ueoka; Yoko      Matsumoto; Koichi      Goto; Hideaki      Ichihara; Yuji      Komizu

doi:10.2174/138161211796355128

Abstract

We have produced hybrid liposomes (HL) which can be prepared by sonication of a mixture of vesicular and micellar molecules in a buffer solution. The physical properties of HL such as size, shape, and membrane fluidity can be controlled by changing the constituents and compositional ratio. We have employed HL for chemotherapy and interesting results are as follows; (A) The uniform and stable structure of HL composed of L-α-dimyristoylphosphatidylcholine (DMPC) and polyoxyethylenedodecyl ether (C12(EO)n) with a diameter of 80 nm was revealed. (B) The remarkable inhibitory effects of HL on the growth of various tumor cells were attained in vitro. (C) Induction of apoptosis by HL was obtained and the pathway of apoptosis induced by HL was clarified. (D) A good correlation between the membrane fluidity of HL and inhibitory effects of HL for tumor cells was obtained. (E) Significantly chemotherapeutic effects were obtained using mice model of carcinoma after the treatment with HL without any side effects in vivo. (F) In clinical applications, prolonged survival and remarkable reduction of neoplasm were attained in patients with lymphoma after the treatment with HL without any side effects after the approval of the bioethics committee.

Keywords: Hybrid liposomes, Antitumor effect, Apoptosis, Chemotherapy, Membrane fluidity, Fusion, endocytosis, exocytosis, Liposomes, phospholipid, enzymological, hydrophobicity, enantioselective, Stereochemical, flavonoids, polyoxyethyleneglycol, antitumor, surfactants, carcinoma, polyoxyethylenealkyl