9-Bromo-noscapine (9-Br-Nos) alters tubulin polymerization in non-small cell lung cancer cells differently from noscapine. However, clinical applications of 9-Br-Nos are limited owing to poor aqueous solubility and high lipophilicity that eventually lead to suboptimal therapeutic efficacy at the site of action. Hence, 9-Br-Nos loaded nanostructured lipid particles (9-Br-Nos-NLPs) were prepared by nanoemulsion method to reduce the particle size below 100 nm. To impart the inhalable and rapid release (RR) attributes, 9-Br-Nos-NLPs were treated with spray dried lactose and effervescent excipients to generate, 9Br-Nos-RR-NLPs. The mean particle and aerodynamic size of 9-Br-Nos-NLPs were measured to be 13.4 +/- 3.2 nm and 23 +/- 1.5 gm, significantly (P < 0.05) lower than 19.4 +/- 6.1 nm and 3.1 +/- 1.8 mu m of 9Br-Nos-RR-NLPs. In addition, zeta-potential of 9-Br-Nos-NLPs was examined to be 9.54 0.16 my, significantly (P <0.05) lower than -7.23 +/- 0.10 mV of 9-Br-Nos-RR-NLPs. Hence, both formulations were found to be optimum for pulmonary delivery through inhalation route of administration. Next, 9-BrNos-RR-NLPs exhibited enhanced cytotoxicity, apoptosis and cellular uptake in A549, lung cancer cells, as compared to 9-Br-Nos-NLPs and 9-Br-Nos suspension. This may be attributed to enhanced drug delivery and internalization character of 9-Br-Nos-RR-NLPs by energy-dependent endocytosis and passive diffusion mechanism. Pharmacokinetic and distribution analysis demonstrated the superiority of 9-Br-Nos-RR-NLPs that exhibited similar to 1.12 and similar to 1.75-folds enhancement in half-life of the drug as compared to 9-BrNos-NLPs and 9-Br-Nos powder following inhalation route. Continuation to this, 9-Br-Nos-RR-NLPs also displayed similar to 3.75-fold increment in half-life of the drug in lungs, as compared to 9-Br-Nos suspension following intravenous route of administration. Furthermore, enhanced drug exposure was measured in terms of AUC(last) in lungs following administration of 9-Br-Nos-RR-NLPs, as compared to 9-Br-Nos-NLPs, 9-Br-Nos powder and 9-Br-Nos suspension. This may be attributed to rapid dispersion, enhanced dissolution and deep lung deposition of nanoparticles following inhalation route. Therefore, inhalable 9-Br-Nos-RR-NLPs claims further in depth in vivo tumor regression study to scale up the technology for clinical applications. (C) 2015 Elsevier Inc. All rights reserved.