Exogenous Surfactant as a Pulmonary Delivery Vehicle for Budesonide In Vivo

Baer, Brandon; McCaig, Lynda; Yamashita, Cory; Veldhuizen, Ruud

BACKGROUND: Lung inflammation is associated with many respiratory conditions. Consequently, anti-inflammatory medications, like glucocorticoids, have become mainstay intrapulmonary therapeutics. However, their effectiveness for treating inflammation occurring in the alveolar regions of the lung is limited by suboptimal delivery. To improve the pulmonary distribution of glucocorticoids, such as budesonide to distal regions of the lung, exogenous surfactant has been proposed as an ideal delivery vehicle for such therapies. It was therefore hypothesized that fortifying an exogenous surfactant (BLES) with budesonide would enhance efficacy for treating pulmonary inflammation in vivo. METHODS: An intratracheal instillation of heat-killed bacteria was used to elicit an inflammatory response in the lungs of male and female rats. Thirty minutes after this initial instillation, either budesonide or BLES combined with budesonide was administered intratracheally. To evaluate the efficacy of surfactant delivery, various markers of inflammation were measured in the bronchoalveolar lavage and lung tissue. RESULTS: Although budesonide exhibited anti-inflammatory effects when administered alone, delivery with BLES enhanced those effects by lowering the lavage neutrophil counts and myeloperoxidase activity in lung tissue. Combining budesonide with BLES was also shown to reduce several other pro-inflammatory mediators. These results were shown across both sexes, with no observed sex differences. CONCLUSION: Based on these findings, it was concluded that exogenous surfactant can enhance the delivery and efficacy of budesonide in vivo.