Targeted nanoparticulate drug delivery system to lungs: A promising approach for pulmonary tuberculosis Sujit Kumar Debnath1, Monalisha Debnath2, S. Saisivam3, Rohit Srivastava1,* *,1Department of Biosciences and Bioengineering Indian Institute of Technology Bombay, Powai, Mumbai, Maharashtra, India; 2Department of Electrical Engineering, Indian Institute of Technology Kharagpur, West Bengal, India; 3Gujarat Technological University, Ahmedabad, Gujarat, India *Corresponding author Tuberculosis is a deadly disease worldwide. According to the WHO, a total of 1.4 million people died from TB in 2019 worldwide. TB is one of the top 10 death-causing diseases. The rising incidence of drug resistance cases becomes a more challenging task for clinicians. Tuberculosis frequently attacks the lungs through the inhalation route and cause pulmonary tuberculosis. Targeted delivery can be possible successfully with the help of a nanoparticulate form of drugs. Polymeric nanoparticles, lipid-nanoparticles, and liposomes are extensively explored in the targeted delivery. We have optimized two polymeric nanoparticles of prothionamide (A model drug): PLGA (50:50) and Chitosan nanoparticles. There are several conventional dosage forms available in the market. But, they are non-specific, and a small fraction of the administered dose reaches the lung. In the lungs targeted delivery, the inhalation route is the ultimate opportunistic to get the desirable therapeutic action. We modified the above two nanoparticles into a dry powder inhaler to make it suitable for pulmonary administration. The devices available for human administration are not suitable for animal administration. Thus, we fabricated the delivery device for DPI using 3D printing. During animal experiments, this delivery device could able to deliver DPI successfully to the trachea part of the rat. After administration, bio-distribution, and lugs pharmacokinetics were assessed. In-vivo, PLGA (50:50) would be able to release 43% of the content, and chitosan would able to release more than 96% of the delivered amount in 24 hours. Both the polymers showed an initial blast effect that rise the plasma and lung concentration above the MIC. This study also demonstrated the drug concentration in the lungs is comparatively high rather than the concentration present in the plasma. Hence, using a DPI inhaler, the drug targeting can be possible to lungs and additionally restrict drug for bio-distribution.