title: Optimizing long-circulating liposomes for delivery of simvastatin to C26 colon carcinoma cells.
abstract: Simvastatin (SIM) is a lipophilic statin that has potential benefits for prevention and treatment of several types of malignancies. However, its low water solubility and the toxicity associated with administration of high doses recommend it for encapsulation in carriers able to deliver the therapeutic dose in the tumor. In this work, liposomes with long-circulating properties were proposed as delivery systems for SIM. The objective of this study was to optimize the formulation of SIM-loaded long-circulating liposomes (LCL-SIM) by using D-optimal experimental design. The influence of phospholipids concentration, phospholipids to cholesterol molar ratio and SIM concentration was studied on SIM liposomal concentration, encapsulation efficiency and liposomal size. The optimized formulation had liposomal SIM concentration 6238 µg/ml, EE % of 83.4% and vesicle size of 190.5 nm. Additionally we evaluated the in vitro cytotoxicity of the optimized liposomal SIM (LCL-SIM-OPT) on C26 murine colon carcinoma cells cultivated in monoculture as well as in co-culture with murine peritoneal macrophages at a cell density ratio that provides an approximation of physiological conditions of colon carcinoma development in vivo. Our preliminary studies suggested that LCL-SIM-OPT exerted cytotoxicity on C26 cells probably via enhancement of oxidative stress in co-culture environment.
authors.affiliation: a Faculty of Pharmacy, Department of Pharmaceutical Technology and Biopharmaceutics , Iuliu Hatieganu University of Medicine and Pharmacy , Cluj-Napoca , Romania .
authors.forename: Alina
authors.initials: A
authors.lastname: Porfire
authors.affiliation: a Faculty of Pharmacy, Department of Pharmaceutical Technology and Biopharmaceutics , Iuliu Hatieganu University of Medicine and Pharmacy , Cluj-Napoca , Romania .
authors.forename: Ioan
authors.initials: I
authors.lastname: Tomuta
authors.affiliation: a Faculty of Pharmacy, Department of Pharmaceutical Technology and Biopharmaceutics , Iuliu Hatieganu University of Medicine and Pharmacy , Cluj-Napoca , Romania .
authors.forename: Dana
authors.initials: D
authors.lastname: Muntean
authors.affiliation: b Faculty of Biology and Geology, Department of Molecular Biology and Biotechnology , Babes-Bolyai University , Cluj-Napoca , Romania , and.|c Molecular Biology Centre, Institute for Interdisciplinary Research in Bio-Nano-Sciences , Babes-Bolyai University , Cluj-Napoca , Romania.
authors.forename: Lavinia
authors.initials: L
authors.lastname: Luca
authors.affiliation: b Faculty of Biology and Geology, Department of Molecular Biology and Biotechnology , Babes-Bolyai University , Cluj-Napoca , Romania , and.|c Molecular Biology Centre, Institute for Interdisciplinary Research in Bio-Nano-Sciences , Babes-Bolyai University , Cluj-Napoca , Romania.
authors.forename: Emilia
authors.initials: E
authors.lastname: Licarete
authors.affiliation: b Faculty of Biology and Geology, Department of Molecular Biology and Biotechnology , Babes-Bolyai University , Cluj-Napoca , Romania , and.|c Molecular Biology Centre, Institute for Interdisciplinary Research in Bio-Nano-Sciences , Babes-Bolyai University , Cluj-Napoca , Romania.
authors.forename: Marius Costel
authors.initials: MC
authors.lastname: Alupei
authors.affiliation: a Faculty of Pharmacy, Department of Pharmaceutical Technology and Biopharmaceutics , Iuliu Hatieganu University of Medicine and Pharmacy , Cluj-Napoca , Romania .
authors.forename: Marcela
authors.initials: M
authors.lastname: Achim
authors.affiliation: a Faculty of Pharmacy, Department of Pharmaceutical Technology and Biopharmaceutics , Iuliu Hatieganu University of Medicine and Pharmacy , Cluj-Napoca , Romania .
authors.forename: Laurian
authors.initials: L
authors.lastname: Vlase
authors.affiliation: b Faculty of Biology and Geology, Department of Molecular Biology and Biotechnology , Babes-Bolyai University , Cluj-Napoca , Romania , and.|c Molecular Biology Centre, Institute for Interdisciplinary Research in Bio-Nano-Sciences , Babes-Bolyai University , Cluj-Napoca , Romania.
authors.forename: Manuela
authors.initials: M
authors.lastname: Banciu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000737:chemistry*; D004354:Drug Screening Assays, Antitumor; D008081:Liposomes; D051379:Mice; D010316:Particle Size; D019821:Simvastatin / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013499:Surface Properties; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008081:Liposomes; D019821:Simvastatin
keywords: Cancer; D-optimal experimental design; cytotoxicity; optimization; statin