Tröger's base-functionalized chitosan: design, synthesis & evaluation for drug delivery and antioxidant applications

To explore the use of Tröger's Base (TB) in conjunction with chitosan (CS) chemistry, we constructed a stable TB-functionalized chitosan (TB@CS) conjugate by covalently linking a TB to chitosan via imine linkages. The structural and chemical characterization of TB@CS was conducted using FT ̶ IR, PXRD, NMR (¹H,¹³C CP/MAS,¹H ̶ ¹H COSY, ¹H-¹³C HSQC/HETCOR), DLS, FE ̶ SEM and zeta potential analyses. The synthesized conjugate exhibited better antioxidant properties against DPPH and ABTS assays than native chitosan. Moreover, DLS & zeta potential analyses of TB@CS revealed a nanometer size range (200.6 nm) and excellent colloidal stability (49.0 ± 4.8 mV) supporting its suitability as a drug delivery system. Curcumin (Cur) was used as a hydrophobic anticancer drug for drug delivery studies. Cur loaded conjugate Cur ̶ TB@CS showed exceptional drug loading efficiency (95.5 ± 1.9%) and drug loading content (31.4 ± 2.5%), probably due to the inherent host-guest chemistry of TBs. In vitro drug release studies demonstrated the pH-dependent behavior of Cur ̶ TB@CS with accelerated release observed under tumor-like acidic conditions compared to physiological pH. The cytotoxicity studies against A549 cancer and PBMCs healthy cell lines, suggested its potential as a promising drug delivery carrier for cancer therapy.