Delivery of Small Molecule EF2 Kinase Inhibitor for Breast and Pancreatic Cancer Cells Using Hyaluronic Acid Based Nanogels

Cömert Önder F., Sağbaş Suner S., Şahiner N., Ay M., Ozpolat B.

PHARMACEUTICAL RESEARCH, vol.37, no.3, 2020 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 37 Issue: 3
  • Publication Date: 2020
  • Doi Number: 10.1007/s11095-020-2774-5
  • Journal Name: PHARMACEUTICAL RESEARCH
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Agricultural & Environmental Science Database, BIOSIS, CAB Abstracts, Chimica, EMBASE, INSPEC, International Pharmaceutical Abstracts, MEDLINE, Veterinary Science Database
  • Keywords: breast and pancreatic cancer, elongation factor 2 kinase, kinase inhibitor, hyaluronic acid-sucrose nanoparticles, targeted therapy
  • Çanakkale Onsekiz Mart University Affiliated: Yes

Abstract

Purpose To evalauted natural polymeric biomaterials including hyaluronic acid (HA) and its copolymeric form HA:Suc nanoparticles (NPs) as drug carrier systems for delivery of hydrophobic small molecule kinase EF2-kinase inhibitor in breast and pancreatic cancer cells. Methods In vitro cellular uptake studies of Rhodamine 6G labaled HA:Suc nanoparticles were evaluated by using flow cytometry analysis and fluorescent microscopy in breast (MDA-MB-231 and MDA-MB-436) and pancreatic cancer cells (PANC-1 and MiaPaca-2). Besides, in vitro release study of compound A (an EF2-kinase inhibitor) as a model hydrophobic drug was performed in the cancer cells. Results These biological evaluation studies indicated that HA and HA:Suc NPs provided a highly effective delivery of compound A were into breast and pancreatic cancer cells, leading to significant inhibition of cell proliferation and colony formation of breast and pancreatic cancer cells. Conclusion HA-sucrose NPs incorporating an EF2-Kinase inhibitor demonstrate significant biologic activity in breast and pancreatic cancer cells. This is the first study that shows natural polymeric drug carriers succesfully deliver a hydrofobic cancer drug into cancer cells.