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The purpose of the present research work was to explore chitosan nanoparticles (NPs) of a novel anti-tubercular drug, bedaquiline (BDQ) in order to reduce dose and side effects associated with oral BDQ formulation. The NPs were fabricated using ionic gelation method and evaluated for particle size, zeta potential, entrapment efficiency and drug loading. Plackett Burman was used as screening design. Two level three-factor factorial design was applied for optimization. Following freeze drying of NPs, the powder obtained was mixed with lactose pre-blend to obtain a respirable powder. In vitro deposition studies were performed using non-viable cascade impactor. In vitro cytotoxicity and in vivo toxicity studies were performed. In vivo pharmacokinetics of NPs formulation was compared with conventional dry powder inhaler (DPI) formulation and oral drug solution. Polymer amount, TPP concentration and probe sonication time were the significant factors. Optimized batch showed particle size of 109.7±9.3nm with a zeta potential of 36±2.1mV. In vitro and in vivo toxicity studies unveiled better safety profile of NPs in comparison to conventional DPI and oral solution. Pharmacokinetic studies manifested higher concentration of BDQ in lungs via developed formulation. Therefore, the developed formulation could efficiently deliver BDQ into the lungs.