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 ± 50 nm in dried state from SEM images and found to increase to about 540 ± 47 nm in DI water measured with DLS measurements. The surface areas of HA and HA:Suc nanogels were measured as 18.07 ± 2.4 and 32.30 ± 6.1 m²/g with porosities of 3.58 ± 1.8, and 9.44 ± 3.1 nm via BET analysis, respectively. The zeta potentials for HA and HA:Suc nanogels were measured as −33 ± 1.4 and − 30 ± 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 ± 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 ± 0.1% hemolysis ratio and 76 ± 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‑(4‑hydroxyphenyl)acryloyl)‑2H‑chromen‑2‑on (A^#) established by our group. The nanogels successfully delivered the model drug A at 10.43 ± 2.12 mg/g for 2 days.