Self-Assembled Thermoresponsive Nanogel from Grafted Hyaluronic Acid as a Biocompatible Delivery Platform for Curcumin with Enhanced Drug Loading and Biological Activities

A hyaluronic acid-grafted poly(N-isopropylacrylamide) (HA-pNIPAM) was synthesized as a polymeric nanogel platform for encapsulation and delivery of hydrophobic bioactive compounds using curcumin as a model drug. As demonstrated by transmission electron microscopy and dynamic light scattering techniques, the HA-pNIPAM was simply assembled into spherical nano-sized particles with the thermoresponsive behavior. The success of curcumin aqueous solubilization was confirmed by fluorescent spectroscopy. The resulting nanogel formulation enhanced the aqueous solubility and uptake into NIH-3T3 cells of curcumin. This nanogel formulation also demonstrates cytocompatibility against NIH-3T3 cells, which deems it safe as a delivery vehicle. Moreover, the formulation has a slight skin-protection effect using an artificial skin equivalence model. The curcumin-loaded HA-pNIPAM nanogel showed an anti-proliferative activity against MDA-MB-231, Caco-2, HepG2, HT-29, and TNF-α-induced hyperproliferation of keratinocyte (HaCaT) cells. The thermoresponsive HA-pNIPAM nanogel reported here could be further optimized as a platform for controlled-release systems to encapsulate pharmaceuticals for therapeutic applications.