Encapsulation and rapid release of nicotine hydrogen tartrate from β-cyclodextrin nanosponges: preparation, characterization, and in vitro evaluation

The development of an oral delivery system enabling rapid release of nicotine salts represents a promising strategy for advancing nicotine replacement therapy. In this study, nicotine hydrogen tartrate inclusion complexes (CDNS-NHT) were fabricated using β-cyclodextrin nanosponges (CDNS) as carriers. We systematically investigated how CDNS synthesized at different β-cyclodextrin (β-CD): diphenyl carbonate (DPC) molar ratios affected drug-loading performance, and the resulting complexes were characterized through multiple analytical techniques. Molecular docking studies revealed a binding energy of -5.492 kcal/mol between nicotine hydrogen tartrate (NHT) and CDNS, demonstrating that inclusion complex formation is thermodynamically favorable. Encapsulation efficiency reached an optimal value of 77.24 ± 6.44% at a β-CD: DPC molar ratio of 1:4. Fourier transform infrared spectroscopy and thermogravimetric analysis confirmed the successful encapsulation of NHT within CDNS, alongside significantly enhanced thermal stability. In vitro release studies demonstrated rapid dissolution characteristics, achieving a cumulative release of 74.00 ± 5.38% within 5 min under simulated oral conditions. Cytotoxicity assays further revealed that CDNS-NHT maintained cell viability exceeding 90% in both human oral keratinocytes (HOK-16B) and oral squamous cell carcinoma cells (SU4-02), indicating its favorable biocompatibility. This delivery system integrates excellent stability, efficient solubilization, and rapid oral release properties, presenting considerable potential for applications in nicotine replacement therapy.