In vivo antitumor effect of cromolyn in PEGylated liposomes for pancreatic cancer

• Published in: Journal of controlled release Vol. 157; no. 2; pp. 190 - 195
• Main Authors: Kim, Cha-Eun, Lim, Sun-Kyung, Kim, Jin-Seok
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier B.V 30.01.2012; Elsevier
• Subjects: adenocarcinoma; Animals; anticarcinogenic activity; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Apoptosis - drug effects; Biological and medical sciences; Cell Line, Tumor; Cell Proliferation - drug effects; cromolyn; Cromolyn Sodium - administration & dosage; Cromolyn Sodium - pharmacology; Cromolyn Sodium - therapeutic use; cytotoxicity; drugs; encapsulation; Female; gemcitabine; General pharmacology; Humans; in vitro studies; Liposomes; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Nude; neoplasm cells; pancreatic cancer; pancreatic neoplasms; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - pathology; PEGylated liposome; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Phosphatidylcholines - chemistry; Polyethylene Glycols - chemistry; proteins; Tumor Burden - drug effects; Xenograft Model Antitumor Assays; PBS; cro; PEG-lipo-cro; pancreatic cancer; TUNEL; cromolyn; gemcitabine; MTT; PEGylated liposome; gem; lipo; Antineoplastic agent; Pharmaceutical technology; Gemcitabine; Liposome; Malignant tumor; In vivo; Antimetabolic; Pancreas cancer; Pyrimidine derivatives; Digestive diseases; Fluorine Organic compounds; Pegylated form; Pyrimidine nucleoside; Cancer; Pancreatic disease
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2011.09.066

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. Improved therapeutic efficacy of PEGylated liposomal cromolyn (PEG-lipo-cro) in BxPC-3 pancreatic cancer xenograft mice. [Display omitted]