Mucoadhesive Chitosan–Gellan Gum Nanoparticles for Rifampicin Delivery: Taguchi Optimization and In Vitro Release Behavior

Background/Objectives: Tuberculosis treatment remains challenging due to the limited stability and side effects of conventional rifampicin formulations. This study aimed to synthesize and optimize mucoadhesive chitosan–gellan gum nanoparticles for improved rifampicin delivery. The novelty of this work was the introduction of ethanol into the synthesis process, which improved the solubility of rifampicin and contributed to the formation of nanoparticles with the desired physicochemical characteristics. Methods: Rifampicin-loaded chitosan–gellan gum nanoparticles were produced using the polyelectrolyte complex coacervation method. The polymer ratios, drug-to-polymer ratio, temperature and ethanol volume were the main factors that were optimized using the Taguchi method. The physicochemical properties, such as TGA, DSC and FTIR spectroscopy, were investigated. In addition, drug release, mucoadhesive properties and mycobacterial activity against the H37Rv strain of Mycobacterium tuberculosis were examined. Results: Optimization using the Taguchi method produced nanoparticles with a narrow particle distribution (PDI: 0.212 ± 0.021), a satisfactory average size (153 ± 3 nm) and stability against aggregation (zeta potential: 22.94 ± 1.30 mV). A study of the degree of rifampicin release from nanoparticles showed that the drug release is influenced by pH and has a prolonged effect. Drug-loaded nanoparticles exhibited increased mucoadhesion compared with the pure drug. The minimum inhibitory concentration of rifampicin in chitosan–gellan gum nanoparticles for the suppression of the H37RV strain of Mycobacterium tuberculosis was determined. Spectroscopic and thermal analyses confirmed the incorporation of rifampicin in the polymer matrix. Conclusions: The developed chitosan–gellan gum nanoparticles represent a promising mucoadhesive delivery system for rifampicin. The incorporation of ethanol and the use of Taguchi optimization provide an effective strategy for controlling nanoparticle properties and improving drug delivery performance.