Context: Inhalation of drugs like salbutamol sulphate (SBS) suffers from low pulmonary deposition due to its micronized size. Objective: (a) to develop submicronic-SBS respiratory fluid, (b) pre-clinical toxicity study, (c) in-vitro and in-vivo evaluation in terms of respiratory fraction, and (d) clinical study to assess safety and efficacy. Methods: Formulation was optimized on basis of particle size and in-vitro nebulization rate. Anderson cascade impaction (ACI) was done to validate its advantage in terms of respirable fraction. Effect on cardiopulmonary parameters (spirometry, pulse-oxymetry, echocardiography and 6-minute walk test) was evaluated and compared with control (n=12). In-vivo pulmonary deposition pattern was compared using gamma scintigraphy. Results: Formulation was optimized with average particle size of 410nm. SBS was radiolabeled with Tc-99m and 99mTc-SBS was found suitable for estimating in-vivo SBS deposition. Preclinical toxicity studies in two-animal species showed no biochemical or behavioural toxicity. In-vitro ACI data showed high respirable fraction (81.7±7.1%) in comparison to control (42.5±3.8%). In-vivo scintigraphy suggested significantly higher pulmonary deposition for test formulation in comparison to control. Better improvement in cardiopulmonary parameters was seen in test treated group. Conclusions: As demonstrated for SBS, nano-sizing may enhance regional pulmonary deposition and provide an attractive therapeutic option for bronchopulmonary disorders like COPD.