Folate-decorated maleilated pullulan-doxorubicin conjugate for active tumor-targeted drug delivery

Eur J Pharm Sci. 2011 Apr 18;42(5):517-26. doi: 10.1016/j.ejps.2011.02.006. Epub 2011 Feb 23.

Abstract

A novel folate-decorated maleilated pullulan-doxorubicin conjugate (abbreviated as FA-MP-DOX) for active tumor targeting was set up. The structure of this conjugate was confirmed by (1)H NMR analysis. Furthermore, the conjugation efficiency, drug release property and stability of the conjugate were determined. The cellular uptake and cytotoxicity were assessed by using ovarian carcinoma A2780 cells as in vitro cell model. In vitro DOX release from FA-MP-DOX conjugate occurred at a faster rate at acidic pH compared to neutral pH (7.4). After 30 h of incubation at pH 2.5, 5.0 and 7.4 the released free DOX was about 68.71%, 50.08% and 26%, respectively. Based on the IC(50) values, the conjugate was found more effective with ovarian carcinoma A2780 cells than the parent drug after 48 h culture. These results suggested that FA-MP-DOX conjugate could be a promising doxorubicin carrier for its targeted and intracellular delivery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibiotics, Antineoplastic / administration & dosage*
  • Antibiotics, Antineoplastic / chemistry
  • Antibiotics, Antineoplastic / pharmacology
  • Cell Culture Techniques
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Doxorubicin / administration & dosage*
  • Doxorubicin / chemistry
  • Doxorubicin / pharmacology
  • Drug Carriers / chemical synthesis
  • Drug Carriers / chemistry*
  • Drug Stability
  • Female
  • Folic Acid / chemistry*
  • Glucans / chemistry*
  • Humans
  • Maleic Anhydrides / chemistry*
  • Microscopy, Fluorescence
  • Molecular Structure
  • Solubility

Substances

  • Antibiotics, Antineoplastic
  • Drug Carriers
  • Glucans
  • Maleic Anhydrides
  • Doxorubicin
  • pullulan
  • Folic Acid