title: In vivo antitumor effect of cromolyn in PEGylated liposomes for pancreatic cancer.
abstract: A PEGylated liposomal formulation of cromolyn, composed of dipalmitoylphosphatidylcholine (DPPC), dimyristoylphosphatidylcholine (DMPC), distearoylphosphatidylcholine (DSPC) and 1,2-distearoyl-sn-glycero-3-phospho-ethanolamine-N-[methoxy(polyethyleneglycol)-2000] (DSPE-mPEG2000), has been developed with the purpose of improving the antitumor activity of cromolyn for human pancreatic adenocarcinoma. In stability study, the amount of proteins adsorbed onto the PEGylated liposomes encapsulating cromolyn was 4.5-fold lower than the non-PEGylated liposome. In vitro study showed that the cromolyn in PEGylated liposome exhibited better anti-proliferative effect in BxPC-3 cells than in Panc-1 cells, which indicates higher level of endogenous S100P protein in BxPC-3 cells than in Panc-1 cells as a target protein for this drug. Moreover, the combination of cromolyn with gemcitabine in PEGylated liposomes demonstrated the strongest cytotoxicity to BxPC-3 pancreatic cancer cells in vitro and the highest anti-tumor activity against the BxPC-3 tumor bearing nude mice in vivo. Thus, this PEGylated liposomal formulation of cromolyn is expected to provide a novel approach to the treatment of pancreatic cancer in the future.
authors.affiliation: College of Pharmacy, Sookmyung Women's University, 53-12 Chungpa-Dong 2-Ga, Yongsan-Gu, Seoul 140-742, Korea.
authors.forename: Cha-Eun
authors.initials: CE
authors.lastname: Kim
authors.forename: Sun-Kyung
authors.initials: SK
authors.lastname: Lim
authors.forename: Jin-Seok
authors.initials: JS
authors.lastname: Kim
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004205:Cromolyn Sodium / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010713:Phosphatidylcholines / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D010713:Phosphatidylcholines; D011092:Polyethylene Glycols; D004205:Cromolyn Sodium