Chitosan-Gellan Gum Nanoparticles for Antituberculosis Drug Encapsulation: Synthesis, Characterization and In Vitro Investigation.

Pulmonary delivery of anti-tuberculosis drugs has emerged as a promising alternative for increasing local drug concentrations whilst minimising side effects. Natural polymers-polysaccharides capable of forming polyelectrolyte complexes (PECs) through electrostatic interactions-show great promise in this field. In this study, mucoadhesive chitosan-gellan gum nanoparticles were developed for the controlled release of isoniazid using the polyelectrolyte complex coacervation method. Parameters such as the chitosan-to-gellan gum ratio and the medium pH were investigated to achieve suitable particle size, polydispersity, surface charge, drug loading and encapsulation efficiency. The morphology of the produced nanoparticles was determined using transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA), which confirmed the formation of nanoscale spherical particles. The mucoadhesive properties were tested on ovine lung tissue using fluorescence retention analysis, whilst in vitro drug release was studied under physiological conditions. Antimycobacterial activity against Mycobacterium tuberculosis H37Rv was assessed using the Mycobacteria Growth Indicator Tube (MGIT) system, followed by subculturing on Löwenstein-Jensen medium. The produced nanoparticles exhibited high mucoadhesion, maintaining prolonged retention on lung tissue. Drug release showed an initial burst followed by sustained release over 24 h. These results demonstrate that CSGG-INH nanoparticles possess sustained drug release, good mucoadhesion to the lungs and high antimycobacterial activity, supporting their further development as potential carriers for pulmonary delivery of anti-tuberculosis drugs.