Microsoft word - pulmatrix abstracts 06.25.2011.doc

ATS C22 - Efficacy Of Fluticasone And Salmeterol In A Novel Inhaled Dry Powder
Delivery Platform
S. Arold, D. Manzanedo, S. Kong, F. Saia, J. Sung, M. Lipp, R.W. Clarke, D.L. Hava, Lexington,
MA, p.A4435

RATIONALE: The efficient delivery of therapeutics at high doses to the airways and lung in dry
powder (DP) form remains a challenge. We are developing a salt-based DP platform using
small diameter particles that are dispersible in a flow rate independent manner. A primary
benefit of the technology is the ability to deliver larger drug payloads than many conventional
DP technologies. The aim of this study was to determine the efficacy of a proof-of-concept DP
formulation comprised of the corticosteroid, fluticasone proprionate (FP, 13.5% w/w), and a long
acting bronchodilator, salmeterol xinafoate (SX, 2.0% w/w), in a rodent model of LPS induced,
acute lung injury.

METHODS: Airway Hyperreactivity: Female Balb/c mice (19-21g) were exposed to 20 minutes
of 0.5 mg/ml nebulized lipopolysaccharide (LPS, Pseudomonas aeruginosa) 24 hours prior to
specific airway resistance measurements (sRaw). sRaw was determined by dual chamber
plethysmography (EMKA technologies, VA). Baseline measurements (5 minutes) were collected
prior to treatment with aerosolized DP FP/SX or placebo (leucine) DP. Following treatment
animals were returned to the plethysmograph and another 5 minutes of measurements were
taken prior to escalating doses of aerosolized methacholine (MCh) delivered in the head
chamber (0, 6.25, 12.5 mg/ml). Inflammation: Mice were treated with aerosolized FP/SX or
leucine control DP 1 hour prior to LPS administration. The mice received 0.3µg of LPS
intranasally in 50µl isotonic saline for inhalation, and 4 hours post LPS administration broncho-
alveolar lavage (BAL) was performed for inflammatory cell counts.

RESULTS: FP/SX dry powder treatment resulted in a decrease in sRaw from untreated
baseline measurements (-27% of baseline). The FP/SX treatment also reduced sRaw (-39%)
compared to post-treatment levels leucine treated control animals. Similarly, FP/SX treatment
reduced sRaw over the duration of MCh challenge, with a sRaw reduction of 33%. Additionally,
treatment with FP/SX in LPS challenged mice resulted in a significant decrease in total
inflammatory cells in the BAL with respect to leucine control (1.11x106 vs. 5.00x105, p<0.001),
primarily a result of reduced neutrophil accumulation.

CONCLUSIONS: Aerosol delivery of FP/SX in a novel DP delivery platform reduced both
inflammation and airway hyperreactivity in a mouse model of acute lung injury. These data
suggest that the technology may be a suitable platform for pulmonary drug delivery and provide
a framework for future work involving the delivery of high drug loads to the airways and/or lung
for a wide range of respiratory conditions.

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Source: http://www.pulmatrix.com/Publications/Pulmatrix_Abstracts_2011_ATS-C22.pdf