title: Intracellular accumulation and cytotoxicity of doxorubicin with different pharmaceutical formulations in human cancer cell lines.
abstract: The structure of both carrier and anticancer drug affects the intracellular fate of a transported drug. The study investigated in vitro intracellular accumulation and cytotoxic activity of doxorubicin-loaded solid lipid nanoparticles (SLN), doxorubicin in pegylated liposomes (Caelyx) and free doxorubicin. Intracellular doxorubicin levels and cytotoxic activity were determined by high performance liquid chromatography with fluorescence detection, and by the trypan blue dye exclusion assay, respectively. Doxorubicin-loaded SLN inhibited cell growth more strongly than either free or liposomal doxorubicin, in human colorectal adenocarcinoma, HT-29, retinoblastoma Y79, and glioblastoma U373 cell lines. The IC50 values for doxorubicin-loaded SLN were significantly lower after 24 h exposure than those for free doxorubicin in all cell lines; after 48 h exposure they were lower than those for liposomal doxorubicin in HT-29 and Y79 cells. The enhanced cytotoxic activity of doxorubicin-loaded SLN was associated with increased drug incorporation in cells: intracellular doxorubicin levels were significantly enhanced after exposure to drug-loaded SLN versus either free or liposomal drug. Rate of intracellular accumulation and cytotoxic activity also differed among different cell lines; in particular, cells of epithelial origin were found to be more sensitive to doxorubicin-loaded SLN. In conclusion, the greater sensitivity of HT-29, Y79, and U373 cells to doxorubicin-loaded SLN than to the other drug formulations may be due to the capability of the delivery system to enhance drug action, through a marked uptake and accumulation of SLN within the cell.
authors.affiliation: Department of Anatomy, Pharmacology and Forensic Medicine, University of Torino, Torino, Italy.
authors.forename: Loredana
authors.initials: L
authors.lastname: Serpe
authors.forename: Marilena
authors.initials: M
authors.lastname: Guido
authors.forename: Roberto
authors.initials: R
authors.lastname: Canaparo
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Muntoni
authors.forename: Roberta
authors.initials: R
authors.lastname: Cavalli
authors.forename: Patrizia
authors.initials: P
authors.lastname: Panzanelli
authors.forename: Carlo
authors.initials: C
authors.lastname: Della Pepal
authors.forename: Alessandro
authors.initials: A
authors.lastname: Bargoni
authors.forename: Alessandro
authors.initials: A
authors.lastname: Mauro
authors.forename: Maria Rosa
authors.initials: MR
authors.lastname: Gasco
authors.forename: Mario
authors.initials: M
authors.lastname: Eandi
authors.forename: Gian Paolo
authors.initials: GP
authors.lastname: Zara
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D004337:Drug Carriers / Q000737:chemistry*; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D008081:Liposomes / Q000737:chemistry*; D049329:Nanostructures / Q000737:chemistry / Q000648:ultrastructure; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D011092:Polyethylene Glycols / Q000737:chemistry*
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D008081:Liposomes; D011092:Polyethylene Glycols; D004317:Doxorubicin