Pharmaceutical Research

, Volume 29, Issue 2, pp 375–383

Palmitoyl Ascorbate Liposomes and Free Ascorbic Acid: Comparison of Anticancer Therapeutic Effects Upon Parenteral Administration

  • Rupa R. Sawant
  • Onkar S. Vaze
  • Tao Wang
  • Gerard G. M. D’Souza
  • Karen Rockwell
  • Keyur Gada
  • Ban-An Khaw
  • Vladimir P. Torchilin
Research Paper

DOI: 10.1007/s11095-011-0557-8

Cite this article as:
Sawant, R.R., Vaze, O.S., Wang, T. et al. Pharm Res (2012) 29: 375. doi:10.1007/s11095-011-0557-8

ABSTRACT

Purpose

To evaluate and compare anticancer therapeutic effect of palmitoyl ascorbate liposomes (PAL) and free ascorbic acid (AA).

Methods

Liposomes incorporating palmitoyl ascorbate (PA) were prepared and evaluated for PA content by HPLC. To elucidate mechanism of action of cell death in vitro, effect of various H2O2 scavengers and metal chelators on PA-mediated cytotoxicity was studied. Effect of various combinations of PAL and free AA on in vitro cytotoxicity was evaluated on 4T1 cells. In vivo, PAL formulation was modified with polyethylene glycol; effect of PEGylation on in vitro cytotoxicity was evaluated. Biodistribution of PEG-PAL formulation was investigated in female Balb/c mice bearing murine mammary carcinoma (4T1 cells). In vivo anticancer activity of PEG-PAL (PEG-PAL equivalent to 20 mg/kg of PA injected intravenously on alternate days) was compared with free AA therapy in same model.

Results

PEG-PAL treatment was significantly more effective than free AA treatment in slowing tumor growth.

Conclusions

Nanoparticle formulations incorporating PA can kill cancer cells in vitro. The mechanism of PA cytotoxicity is based on production of extracellular reactive oxygen species and involves intracellular transition metals.

KEY WORDS

ascorbic acidcancerliposomespalmitoyl ascorbate

ABBREVIATIONS

AA

ascorbic acid

DHAA

dehydroascorbic acid

DFO

desferrioxamine mesylate

DMEM

Dulbecco’s Modified Eagle Medium

DTPA-PE

1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-diethylenetriaminepentaacetic acid

EDTA

ethylenediaminetetraacetic acid

FBS

fetal bovine serum

GLUTs

glucose transporters

HIF

hypoxia-inducible factors

PA

palmitoyl ascorbate

PAL

palmitoyl ascorbate liposomes

PEG2000-PE

1, 2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (poly (ethylene glycol))-2000] (PEG2000-PE)

PL

plain liposomes

ROS

reactive oxygen species

SOD

superoxide dismutase

TCEP

tris(2-carboxyethyl) phosphine hydrochloride

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Rupa R. Sawant
    • 1
  • Onkar S. Vaze
    • 1
  • Tao Wang
    • 1
  • Gerard G. M. D’Souza
    • 1
    • 2
  • Karen Rockwell
    • 1
  • Keyur Gada
    • 1
  • Ban-An Khaw
    • 1
  • Vladimir P. Torchilin
    • 1
  1. 1.Center for Pharmaceutical Biotechnology and NanomedicineNortheastern UniversityBostonUSA
  2. 2.Department of Pharmaceutical SciencesMassachusetts College of Pharmacy and Health SciencesBostonUSA