Incorporation of rosuvastatin-loaded chitosan/chondroitin sulfate nanoparticles into a thermosensitive hydrogel for bone tissue engineering: preparation, characterization, and cellular behavior

Rosuvastatin (RSV) has been shown to have significant impact on the simulation of bone regeneration after local injection. The current study aimed to develop a localized controlled delivery system from RSV by incorporating RSV-loaded chitosan/chondroitin sulfate (CTS/CS) nanoparticles into thermosensitive Pluronic F127/hyaluronic acid (PF127/HA) hydrogel. RSV-loaded CTS/CS nanoparticles were prepared by ionic gelation, and the impact of various formulation variables was assessed using the Box-Behnken design. Consequently, optimized RSV-loaded nanoparticles were incorporated into the PF127/HA hydrogel. Rheological properties, degradation rates of hydrogels, and the release rate of RSV from hydrogel were examined. Mean particle size, zeta potential, entrapment efficiency, and mean release time of the optimized RSV-loaded nanoparticles were confirmed as 283.2 ± 16 nm, -31.2 ± 6.8 mV, 63.1 ± 4.2%, and 6.14 ± 0.3 h, respectively. The hydrogel containing 3% w/v CTS/CS nanoparticles existed as a solution with low viscosity at room temperature converted to a semisolid upon increasing the temperature to 35 °C. Hydrogel engrafted with CTS/CS showed controlled release of RSV during 48 h with superior in vitro gel stability. As revealed by cytotoxicity and mineralization assays, incorporation of RSV-loaded particles into PF127/HA hydrogel led to improvement in osteoblast viability and proliferation.