Pharmaceutical Research

, Volume 23, Issue 12, pp 2809–2817 | Cite as

Development of 5-FU and Doxorubicin-Loaded Cationic Liposomes against Human Pancreatic Cancer: Implications for Tumor Vascular Targeting

  • Ashish V. Kalra
  • Robert B. Campbell
Research Paper



Human pancreatic adenocarcinoma is a major leading cause of cancer mortality in the United States. Given that current strategies are relatively ineffective against this disease, new treatments are being developed. Liposomes possessing relatively high cationic lipid content preferentially accumulate in tumor angiogenic vessels compared to vessels in normal tissues. We therefore seek to develop cationic liposomes for targeting pancreatic tumor vessels.

Materials and Methods

We report development of 5-fluorouracil (5-FU) and doxorubicin hydrochloride (DOX) loaded in PEGylated cationic liposomes (PCLs). We evaluate cell association, intracellular fate, and cytotoxicity. Human pancreatic cancer cells HPAF-II and Capan-1, and endothelial cells HMEC-1 and HUVEC were used in this study. Intratumoral distribution of PCLs in (HPAF-II) tumors was determined by intravital microscopy.


HUVEC and HMEC-1 were most susceptible to 5-FU after 24 and 48 h, compared to HPAF-II and Capan-1. We observed >90% incorporation of 5-FU and DOX in PCLs for 3–20 mol% preparations, with reduced incorporation for >20 mol% formulations. PCLs showed significantly higher association with human endothelial versus pancreatic cancer cells, and improved growth inhibitory properties of DOX. Intravital microscopy revealed distribution of PCLs along HPAF-II vessels.


Targeting human pancreatic cancer with PCLs may represent a rational alternative to conventional strategies.

Key words

cationic liposomes doxorubicin hydrochloride drug delivery pancreatic cancer 5-fluorouracil 


Capan-1 and HPAF-II

human pancreatic cancer cells










doxorubicin hydrochloride


endothelial cell basal medium


fluorescein isothiocyanate-dextran


human microvascular endothelial cells


human umbilical vein endothelial cell


eagle’s minimum essential medium


phosphate buffer saline


PEGylated cationic liposomes




severe combined immunodeficient




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Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  1. 1.Department of Pharmaceutical Sciences, Bouvé College of Health SciencesNortheastern UniversityBostonUSA

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