Exogenous Surfactant as a Pulmonary Delivery Vehicle for Budesonide In Vivo

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.

Beyond the Interface: Improved Pulmonary Surfactant-Assisted Drug Delivery through Surface-Associated Structures

“…This drug is a glucocorticoid with a potent local anti-inflammatory action typically used to treat or reduce the incidence of different lung diseases, especially in preterm infants [ 25 , 26 ]. The interaction of BUD with PS and the PS-promoted improvement in its distribution have been already confirmed by other researchers [ 10 , 20 , 25 ].…”

“…The use of PS for different drug delivery strategies has been explored by many researchers with different targets [ 10 , 11 , 12 , 13 ]. Apart from the suitability of PS composition to efficiently solubilise poorly water-soluble molecules [ 14 ], the main reason why this material improves the distribution of drugs over the respiratory surface has to do with its capability to rapidly spread along air–liquid interfaces.…”

The Miracles of Surfactant: Less Invasive Surfactant Administration, Nebulization, and Carrier of Topical Drugs

“…Biophysical and chemical stability of surfactant/ budesonide has been evaluated in a number of experimental studies confirming pulmonary and systemic antiinflammatory effects of this strategy in adult rabbits [95], mechanically ventilated preterm lambs [96], and rats [97]. In preterm neonatal rabbits, the combined administration attenuated hyperoxia-induced lung injury [98].…”

The concentration-dependent effect of hydrocortisone on the structure of model lung surfactant monolayer by using an in silico approach

“… 31 Furthermore, the delivery of corticosteroid to the alveoli and their incorporation into endogenous lung surfactants might be improved by incorporating the drug into exogenous surfactants. 32 While the main therapeutic target of corticosteroids is receptors, inhaled drugs can reach the LSM, where they alter the structure and dynamics of the monolayer with detrimental effects on normal lung function. Thus, exogenous lung surfactants might improve corticosteroid delivery and reduce side effects of inhaled glucocorticoids.…”