Development of 3D-printed granisetron hydrogels with temperature-sensitive drug release

Chemotherapy-induced nausea and vomiting (CINV) significantly impair patient quality of life and often complicate oral drug administration. Granisetron hydrochloride, a selective 5-HT3 receptor antagonist, is clinically effective, but conventional oral and intravenous formulations present practical limitations. In this study, a temperature-responsive transdermal hydrogel system based on Pluronic F127 and sodium hyaluronate (HA) was developed and engineered using pressure-assisted microsyringe (PAM) 3D printing to achieve controlled in vitro drug release. Hydrogels containing different ratios of low- and high-molecular-weight HA were prepared and characterized. A lecithin-based dispersion was incorporated to improve drug solubilization and ensure homogeneous distribution within the aqueous matrix. The formulation containing predominantly high-molecular-weight HA exhibited the most favorable release profile in manually prepared samples. The optimized composition was subsequently fabricated via PAM 3D printing to standardize geometry and diffusion path length. The 3D-printed hydrogels demonstrated reproducible and temperature-dependent release behavior, reaching complete drug release within the experimental time frame at 37 °C. Kinetic analysis indicated a highly linear release profile within the investigated time window, consistent with diffusion-controlled release approximating zero-order behavior. These findings demonstrate that PAM 3D printing can serve as an engineering tool to regulate hydrogel architecture and improve release predictability. The developed system represents a structurally tunable and temperature-responsive platform for transdermal granisetron delivery.