title: Long-Circulating Curcumin-Loaded Liposome Formulations with High Incorporation Efficiency, Stability and Anticancer Activity towards Pancreatic Adenocarcinoma Cell Lines In Vitro.
abstract: The incorporation of hydrophobic drugs into liposomes improve their bioavailability and leads to increased stability and anticancer activity, along with decreased drug toxicity. Curcumin (Cur) is a natural polyphenol compound with a potent anticancer activity in pancreatic adenocarcinoma (PA). In the present study, different types of Cur-loaded liposomal formulations were prepared and characterized in terms of size, shape, zeta potential, optimal drug-to-lipid ratio and stability at 4°C, 37°C; and in human plasma in vitro. The best formulation in terms of these parameters was PEGylated, cholesterol-free formulation based upon hydrogenated soya PC (HSPC:DSPE-PEG2000:Cur, termed H5), which had a 0.05/10 molar ratio of drug-to-lipid, was found to be stable and had a 96% Cur incorporation efficiency. All Cur-loaded liposomal formulations had potent anticancer activity on the PA cancer cell lines AsPC-1 and BxPC-3, and were less toxic to a normal cell line (NHDF). Furthermore, apoptosis-induction induced by Cur in PA cells was associated with morphological changes including cell shrinkage, cytoplasmic blebbing, irregularity in shape and the externalization of cell membrane phosphatidylserine, which was preceded by an increase in intracellular reactive oxygen species (ROS) generation and caspase 3/7 activation. Because the liposomal formulations tested here, especially the H5 variant which exhibited slow release of the Cur in the human plasma test, the formulation may be stable enough to facilitate the accumulation of pharmacologically active amounts of Cur in target cancer tissue by EPR. Therefore, our formulations could serve as a promising therapeutic approach for pancreatic cancer and other cancers.
authors.affiliation: Department of Lipids and Liposomes, Faculty of Biotechnology, University of Wroclaw, Wroclaw, Poland.
authors.forename: Mohamed
authors.identifier: 0000-0003-3237-7999
authors.initials: M
authors.lastname: Mahmud
authors.affiliation: Department of Lipids and Liposomes, Faculty of Biotechnology, University of Wroclaw, Wroclaw, Poland.
authors.forename: Adriana
authors.initials: A
authors.lastname: Piwoni
authors.affiliation: Department of Lipids and Liposomes, Faculty of Biotechnology, University of Wroclaw, Wroclaw, Poland.
authors.forename: Nina
authors.initials: N
authors.lastname: Filipczak
authors.affiliation: Department of Lipids and Liposomes, Faculty of Biotechnology, University of Wroclaw, Wroclaw, Poland.
authors.forename: Martyna
authors.initials: M
authors.lastname: Janicka
authors.affiliation: Department of Lipids and Liposomes, Faculty of Biotechnology, University of Wroclaw, Wroclaw, Poland.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Gubernator
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D008081:Liposomes / Q000737:chemistry; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: C519184:1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 2000); D000970:Antineoplastic Agents; D008081:Liposomes; D010714:Phosphatidylethanolamines; D017382:Reactive Oxygen Species; D011092:Polyethylene Glycols; D003474:Curcumin