Nanoscale Res Lett (2009) 4:254–261 DOI 10.1007/s11671-008-9234-1 N A N O E X P R E S S Evaluation of Aerosol Delivery of Nanosuspension for Pre-clinical Pulmonary Drug Delivery Po-Chang Chiang Æ Jason W. Alsup Æ Yurong Lai Æ Yiding Hu Æ Bruce R. Heyde Æ David Tung Received: 6 November 2008 / Accepted: 15 December 2008 / Published online: 6 January 2009 to the authors 2008 Abstract Asthma and chronic obstructive pulmonary disease (COPD) are pulmonary diseases that are charac- terized by inﬂammatory cell inﬁltration, cytokine production, and airway hyper-reactivity. Most of the effector cells responsible for these pathologies reside in the lungs. One of the most direct ways to deliver drugs to the target cells is via the trachea. In a pre-clinical setting, this can be achieved via intratracheal (IT), intranasal (IN), or aerosol delivery in the desired animal model. In this study, we pioneered the aerosol delivery of a nanosuspension formulation in a rodent model. The efﬁciency of different dosing techniques and formulations to target the lungs were compared, and ﬂuticasone was used as the model com- pound. For the aerosol particle size determination, a ten- stage cascade impactor was used. The mass median aero- dynamic diameter (MMAD) was calculated based on the percent cumulative accumulation at each stage. Formula- tions with different particle size of ﬂuticasone were made for evaluation. The compatibility of regular ﬂuticasone suspension and nanosuspension for aerosol delivery was also investigated. The in vivo studies were conducted on mice with optimized setting. It was found that the aerosol delivery of ﬂuticasone with nanosuspension was as P.-C. Chiang (&) J. W. Alsup Y. Lai Y. Hu B. R. Heyde D. Tung (&) Global Research and Development, Pharmaceutical Research and Development, St. Louis Laboratories, Pﬁzer Inc, 700 Chesterﬁeld parkway N. T2F, Chesterﬁeld, MO, USA e-mail: Po-chang.chiang@pﬁzer.com D. Tung e-mail: Dvaid.Tung@pﬁzer.com 123 efﬁcient as intranasal (IN) dosing, and was able to achieve dose dependent lung deposition. Keywords Lung inﬂammation Intratracheal Intranasal Aerosol Particle size Pre-clinical Impactor Nano-suspension Introduction Pulmonary diseases, such as chronic obstructive pulmonary disease (COPD) and asthma are complex human airway diseases which affect millions of people worldwide. These human airway diseases are characterized by a strong lung inﬂammatory component with inﬂammatory cell inﬁltra- tion, cytokine production, and airway hyper-reactivity. Pulmonary disease populations are continuously increasing worldwide. More than 6% of the total US pop- ulation suffered from asthma in 2004, up from a little over 3% in 1980. For these patients, glucocorticoids are often prescribed as ﬁrst-line therapy to control symptoms, improve lung function, and reduce morbidity and mortality [1]. A treatment option for severe asthmatics is continuous or near continuous oral steroids (prednisolone). However, long-term use of high-dose ICS therapy has the potential to cause undesirable side effects. Side effects such as impaired growth in children, decreased bone mineral density, cataracts, skin thinning and bruising, glucose metabolism, and other hypothalamic–pituitary–adrenal- axis (HPA-axis) suppression effects are widely reported [1–5]. Multiple studies have demonstrated that the side effects of glucocorticoid therapy for human airway dis- eases are related to the systemic exposure of the drugs. More importantly, receptors responsible for efﬁcacy in the lungs are also expressed in systemic tissues which are