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

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. Graphical Abstract Nanoparticles based on HA:Suc are effective in delivering hydrofobic cancer drugs in breast and pancreatic cancers.

Hyaluronic acid and hyaluronic acid: Sucrose nanogels for hydrophobic cancer drug delivery.

Porous and biodegradable hyaluronic acid (HA) nanogel and their copolymeric forms with sucrose (Suc), HA:Sucrose (HA:Suc) nanogels, were synthesized by employing glycerol diglycidyl ether (GDE) as crosslinker with a single step reaction in surfactant-free medium. The size of the nanogels was determined as 150 ±â€¯50 nm in dried state from SEM images and found to increase to about 540 ±â€¯47 nm in DI water measured with DLS measurements. The surface areas of HA and HA:Suc nanogels were measured as 18.07 ±â€¯2.4 and 32.30 ±â€¯6.1 m2/g with porosities of 3.58 ±â€¯1.8, and 9.44 ±â€¯3.1 nm via BET analysis, respectively. The zeta potentials for HA and HA:Suc nanogels were measured as -33 ±â€¯1.4 and - 30 ±â€¯1.2 mV, respectively. The thermal degradation of both types of nanogels revealed similar trends, while hydrolytic degradation of the nanogels was about 22.7 ±â€¯0.2 wt% in 15 days. Both HA and HA:Suc nanogels were stable in blood up to 250 µg/mL concentration with approximately 0.5 ±â€¯0.1% hemolysis ratio and 76 ±â€¯12% blood clotting indices, respectively. Finally, these nanogels were used as a sustained slow-release or long-term delivery system over 2 days for a hydrophobic cancer drug, 3­((E)­3­(4­hydroxyphenyl)acryloyl)­2H­chromen­2­on (A#) established by our group. The nanogels successfully delivered the model drug A at 10.43 ±â€¯2.12 mg/g for 2 days.