ABSTRACT
Inhibitory effects of HL-n composed of 95 mol% L-α-dimyristoylphosphatidylcholin (DMPC) and 5 mol% polyoxyethylenedodecylether (C(12)(EO)(n), n = 21, 23, or 25) on the growth of human rheumatoid arthritis (RA) fibroblast-like synoviocytes (HFLS-RA) in vitro were examined. Remarkably high inhibitory effects of HL-n on the growth of HFLS-RA cells were obtained. The induction of apoptosis by HL-n was revealed on the basis of TUNEL method. Furthermore, the therapeutic effects of HL-23 using mouse models of arthritis were investigated. Therapeutic effects without joint swelling were obtained in mouse models of RA treated with HL.
Subject(s)
Arthritis, Rheumatoid/drug therapy , Liposomes/chemistry , Synovial Membrane/cytology , Animals , Apoptosis , Dimyristoylphosphatidylcholine/chemistry , Disease Models, Animal , Humans , Liposomes/therapeutic use , Mice , Polidocanol , Polyethylene Glycols/chemistryABSTRACT
Cationic hybrid liposomes (HL) can be prepared by simply ultrasonicating a mixture of L-alpha-dimyristoylphosphatidylcholine (DMPC), polyoxyethylene (21)dodecyl ether (C(12)(EO)(21)) and O,O'-ditetradecanoyl-N-(alpha-trimethylammonioacetyl) diethanolamine chloride (2C(14)ECl) in a buffer solution. The inhibitory effects of cationic HL containing 2C(14)ECl on the growth of OS-RC-2 human renal carcinoma cells in vitro and in vivo were examined. The 50% inhibitory concentration of cationic HL was remarkably reduced compared with that of DMPC liposomes. Induction of apoptosis by cationic HL in OS-RC-2 cells was verified on the basis of flow cytometric analysis and fluorescence microscopy in vitro. In addition, the effects on survival of cationic HL along with apoptosis in vivo were obtained using a mouse model of renal carcinoma. Chemotherapy with drug-free cationic HL for renal cell carcinoma was developed for the first time through the interaction between cationic HL and anionic surface region of tumor cell membranes, without any side-effects. The results obtained might be applied in chemotherapies used at present for patients with renal carcinoma.