<scp>pH</scp> ‐responsive supramolecular vesicles composed of sulfobutylether‐β‐cyclodextrin and <i>N</i> ‐dodecyl chitosan for controlled release of naproxen sodium

Abstract pH‐responsive supramolecular polymeric vesicles were successfully developed through the host–guest complexation of two biocompatible and water‐soluble saccharides: sulfobutylether‐β‐cyclodextrin (SCD) and N ‐dodecyl chitosan (DCS). Extensive characterization using UV–vis spectroscopy, dynamic light scattering (DLS), zeta potential measurements, and transmission electron microscopy (TEM) confirmed the structural robustness of the vesicles, which exhibited effective self‐assembly in acidic conditions and disassembly in alkaline environments. To evaluate the drug‐loading capacity and pH‐responsive release properties, naproxen sodium (NS), a widely used nonsteroidal anti‐inflammatory drug, was encapsulated as a model compound. In vitro release studies simulating gastrointestinal pH conditions (2.0, 6.8, and 8.5) demonstrated minimal drug release of (28.34 ± 1.02)% at low pH and significantly enhanced release of (56.57 ± 1.68)% and (86.96 ± 1.29)% at neutral and slightly alkaline pH, respectively. The system exhibited an initial burst release followed by sustained release, aligning with the therapeutic requirements for rapid onset and prolonged action. These findings highlight the potential of SCD/DCS supramolecular vesicles as a versatile platform for targeted oral drug delivery, particularly for drugs requiring intestinal release. Highlights Supramolecular vesicles self‐assembled via sulfobutylether‐β‐cyclodextrin (SCD) and N ‐dodecyl chitosan (DCS) host–guest complexation. Vesicles exhibited stability in acidic pH and disassembled in alkaline conditions. Naproxen sodium‐loaded vesicles displayed pH‐sensitive release properties. Drug release occurred in neutral to alkaline pH, ideal for intestinal delivery.