Levan enhanced the NF-kappa B suppression activity of an oral nano PLGA-curcumin formulation in breast cancer treatment


Eskandari Z., BAHADORİ F., YENİGÜN V. B. , Demiray M., EROĞLU M. S. , KOÇYİĞİT A., ...More

INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES, vol.189, pp.223-231, 2021 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 189
  • Publication Date: 2021
  • Doi Number: 10.1016/j.ijbiomac.2021.08.115
  • Title of Journal : INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
  • Page Numbers: pp.223-231
  • Keywords: Levan, Curcumin, Gemcitabine, NF-kappa B, Oral nano drug delivery, PLGA, PANCREATIC-CANCER, GEMCITABINE, NANOPARTICLES, MODEL, INHIBITION, SOLUBILITY, COPOLYMER, APOPTOSIS, MICELLES, CELLS

Abstract

Chemoresistance (CR) is one of the reasons why chemotherapy agents like Gemcitabine (GMC) remain insufficient in healing breast cancer. Activation of Nuclear Factor-kappa B (NF-kappa B) during chemotherapy is known as an important factor in the development of CR. The hydrophobic polyphenol curcumin is shown to inhibit NF-kappa B and hence CR. The aim of this work was to increase the poor bioavailability of curcumin by loading it into the nano-micelles made of Poly (Lactide-co-Glycolide) (PLGA) and levan, where levan as a natural fructose homopolymer makes the nano-micelle more stable and increases its uptake using the fructose moieties. In this study, a PLGA-levan-curcumin formulation (PLC) was designed and characterized. The size was measured as 154.16 +/- 1.45 nm with a 67.68% encapsulation efficiency (EE%). The incorporation between the components was approved. Levan made the nano-micelles stable for at least three months, increased their uptake, and led to a 10,000-fold increase in the solubility of curcumin. The enhanced bioavailability of curcumin reduced the NF-kappa B levels elevated by GMC, both in vitro and in vivo. The PLC showed a complete tumor treatment, while GMC only showed a rate of 52%. These point to the great potential of the PLC to be used simultaneously with chemotherapy.