title: Enhanced killing of human epidermoid carcinoma (KB) cells by treatment with ricin encapsulated into sterically stabilized liposomes in combination with monensin.
abstract: Ricin was encapsulated in various charged liposomes having 5 mol% PEG of different chain length on the surface. The cytotoxicity of ricin entrapped in these liposomal formulations was examined in human epidermoid carcinoma (KB) cells with a view to develop an optimum delivery system for ricin in vivo. It was observed that the cytotoxicity of ricin entrapped in various charged liposomes was significantly dependent on the surface charge as well as chain length of PEG. The maximum cytotoxicity of ricin was observed when it was delivered through negatively charged liposomes having 5 mol% PEG-2000 on the surface. Monensin enhances the cytotoxicity of ricin entrapped in various charged liposomes depending on the surface charge. Maximum potentiation of cytotoxicity of ricin was observed when it was delivered through negatively charged liposomes having 5 mol% PEG-2000 on the surface. Studies on the kinetics of inhibition of protein synthesis by ricin revealed that the lag period of inhibition of protein synthesis is significantly lengthened following its delivery through various charged liposomes. Monensin significantly reduced the lag period of action of ricin. It was also observed that the efficacies of monensin on the enhancement of cytotoxicity of ricin entrapped in various charged PEG-liposomes were highly related to their amount of cell association. The current study has demonstrated that by suitable adjustment of charge, density, and chain length of PEG on the surface of liposomes it would be possible to direct liposomal ricin to human tumor cells for their selective elimination in combination with monensin.
authors: Department of Biochemistry, University of Delhi South Campus, Benito Juarez Road, New Delhi-110021, India.
authors: Nikhil
authors: N
authors: Tyagi
authors: Shailendra Singh
authors: SS
authors: Rathore
authors: Prahlad C
authors: PC
authors: Ghosh
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000737:chemistry; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods; D016503:Drug Delivery Systems / Q000379:methods; D004347:Drug Interactions; D006801:Humans; D007624:KB Cells; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry; D008985:Monensin / Q000008:administration & dosage* / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011500:Protein Synthesis Inhibitors / Q000008:administration & dosage / Q000737:chemistry; D012276:Ricin / Q000008:administration & dosage* / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D008081:Liposomes; D011500:Protein Synthesis Inhibitors; D011092:Polyethylene Glycols; D012276:Ricin; D008985:Monensin