Starch/Staerke, vol.78, no.4, 2026 (SCI-Expanded, Scopus)
The aim of this study is to design and evaluate β-cyclodextrin (βCD)-based nanosponges (NSs) capable of both structurally stable and biologically active hydroxyurea conjugation for potential therapeutic use. To this end, nanosponges were synthesized using maleic anhydride (MA), epichlorohydrin (EPI), and their combination (MA-EPI) as crosslinkers. Halloysite nanotubes (HNTs) were incorporated via both in situ and ex situ methods to enhance viscoleasticity, thermal stability, and surface functionality. Dynamic mechanical analysis (DMA) revealed significantly improved storage modulus (E') and glass transition temperature (Tg) values in HNT-reinforced MA-EPI systems, indicating superior elastic behavior and crosslinking density. Thermogravimetric analysis (TGA) demonstrated enhanced thermal stability and multi-step degradation in drug-conjugated structures, with decomposition extending up to 700°C. Cytotoxicity assays using Human Embryonic Kidney 293 (HEK293) cells over 24 and 48 h showed that nanosponge-hydroxyurea conjugates exhibit strong time- and dose-dependent cytotoxic effects, with an IC50 around 20 µg/mL at 48 h in in situ HNT-based structures. Overall, this study establishes a structurally reinforced and biologically effective nanosponge platform for hydroxyurea immobilization, combining enhanced thermo-mechanical properties with controlled cytotoxic performance, thus offering great promise for biomedical applications.