Exogenous Surfactant as a Pulmonary Delivery Vehicle for Budesonide In Vivo
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PULMONARY DRUG DELIVERY
Exogenous Surfactant as a Pulmonary Delivery Vehicle for Budesonide In Vivo Brandon Baer1 · Lynda McCaig1 · Cory Yamashita1,2 · Ruud Veldhuizen1,2 Received: 24 July 2020 / Accepted: 14 October 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract 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. Keywords Exogenous surfactant · Glucocorticoids · Pulmonary inflammation · Drug delivery
Introduction Inflammation is associated with many respiratory conditions, including Asthma, Pneumonia, Bronchopulmonary Dysplasia, Chronic Obstructive Pulmonary Disease, and Acute Respiratory Distress Syndrome (ARDS). However, the effectiveness of anti-inflammatory medications, such as glucocorticoids, is location specific for these conditions in terms of airway (bronchi) or airspace (alveolar) involvement [1]. In Asthma, for example, inflammation is observed primarily in the small airways, which allows for a more direct * Brandon Baer [email protected] 1
Department of Physiology and Pharmacology, Western University, London, ON, Canada
Department of Medicine, Western University, London, ON, Canada
2
delivery of therapeutics, as evidenced by the effectiveness of standard inhalers [1, 2]. On the other hand, in other conditions, such as ARDS and Pneumonia, inflammation occurs in the more distal, alveolar, regions of the lung, where the large surface area, and associated regions of alveolar edema or airway collapse
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