Mannosylated chitosan-decorated PLGA nanoparticles for targeted pulmonary delivery of Isoniazid: A promising approach in the treatment of Tuberculosis.

Tuberculosis (TB), caused by <i>Mycobacterium tuberculosis</i> (M. tb), represents a significant challenge to global health. The management of the disease requires an extended course of antibiotic therapy, spanning a duration of 6 to 9 months. The complexity and duration of these regimens frequently lead to significant adverse effects, gastrointestinal issues, and the development of drug resistance. To address these challenges, the nanoparticulate based inhalable drug delivery system was designed as such by synthesizing mannosylated chitosan decorated PLGA nanoparticles loaded with isoniazid (MC-PLGA-INH-PNPs) for targeted pulmonary delivery. Hence, nanoparticle based drug delivery system offers the potential to target and deliver the loaded drug directly into the M.tb infected cells. The prepared and optimized nano-formulation had a particle size of 154.9 ± 21 nm, zeta potential -23.2 ± 0.52 mV and entrapment efficiency of 79.8% ± 0.45. Additionally, the MC-PLGA-INH-PNPs exhibited a sustained drug release profile at physiological pH 7.4 for a period of 24 hr. An <i>in vivo</i> study of the MC-PLGA-INH-PNPs was performed on a mouse model utilizing lipopolysaccharide as an inducer. The data obtained from the <i>in vivo</i> studies showed substantial improvements in lung tissues architecture and reduced inflammation. The group of animals treated with the MC-PLGA-INH-PNPs showed significant improvement in restoration of the disease when compared to pure drug treated group. These findings further indicate that these inhalable MC-PLGA-INH-PNPs hold a promising strategy for the treatment of tuberculosis and considerably improves pulmonary drug delivery to the target site. However, detailed investigations and testing of this nano-formulation on other relevant animal models will be essential to successfully translate this concept from laboratory to clinical practice.