Intracellular accumulation and cytotoxicity of doxorubicin with different pharmaceutical formulations in human cancer cell lines

Loredana Serpe, Marilena Guido, Roberto Canaparo, Elisabetta Muntoni, Roberta Cavalli, Patrizia Panzanelli, Carlo Della Pepa, Alessandro Bargoni, Alessandro Mauro, Maria Rosa Gasco, Mario Eandi, Gian Paolo Zara

Research output: Contribution to journalArticlepeer-review


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 IC 50, 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.

Original languageEnglish
Pages (from-to)3062-3069
Number of pages8
JournalJournal of Nanoscience and Nanotechnology
Issue number9-10
Publication statusPublished - Sep 2006


  • Doxorubicin
  • Liposomes
  • Solid Lipid Nanoparticles

ASJC Scopus subject areas

  • Chemistry(all)
  • Materials Science(all)
  • Materials Science (miscellaneous)
  • Engineering (miscellaneous)


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