title: Enhanced antitumor activity of different double arms polyethyleneglycol-modified liposomal doxorubicin.
abstract: The effect of polyethyleneglycol (PEG)-modified liposome as a drug carrier has been demonstrated clinically. We designed and synthesized a novel PEG-lipid, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-PEG (different double arms PEG, DDA-PEG) which had two PEG chains of 500 and 2000 in one molecule to develop more useful PEG-modified liposome. DDA-PEG-modified liposomal doxorubicin (DDA-LDOX(7.5)) had the biggest fixed aqueous layer thickness (FALT) compared with other PEG-lipid-modified liposomes even if the added amount was a few. It was thought that FALT was the indication of blood circulation time. In DOX uptake in tumor cells, DDA-LDOX(7.5) group increased the DOX concentration in tumor cells because it had contact ability with tumor cells. Hence, DDA-LDOX(7.5) which has long circulation time in the bloodstream and contact ability with tumor cells, also had a strong antitumor effect on mice bearing M5076 ovarian sarcoma cells which were DOX low sensitive cells according to the expression of multidrug resistance protein. Furthermore, this liposome maintained a high DOX concentration in a tumor for a long time. These results indicated that the useful antitumor effect of DDA-LDOX(7.5) against M5076 ovarian sarcoma cells is a promising DDS carrier for therapies against drug resistant tumors.
authors.affiliation: School of Pharmacy, Iwate Medical University, 2-1-1 Nishitokuta, Shiwa-gun, Iwate 028-3694, Japan. isugiym@iwate-med.ac.jp
authors.forename: Ikumi
authors.initials: I
authors.lastname: Sugiyama
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Sadzuka
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D004337:Drug Carriers / Q000737:chemistry*; D019008:Drug Resistance, Neoplasm; D005260:Female; D008081:Liposomes; D008297:Male; D051379:Mice; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000473:pathology; D010714:Phosphatidylethanolamines / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D012509:Sarcoma / Q000188:drug therapy / Q000473:pathology; D013997:Time Factors
chemical_list: C519184:1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 2000); D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D008081:Liposomes; D010714:Phosphatidylethanolamines; D011092:Polyethylene Glycols; D004317:Doxorubicin