New insights into exogenous surfactant as a carrier of pulmonary therapeutics

Baer, Brandon; Souza, Lucas Miguel Pereira; Pimentel, André Silva; Veldhuizen, Ruud A. W.

doi:10.1016/j.bcp.2019.03.036

Cited by 37 publications

(32 citation statements)

References 102 publications

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“…Several previous studies have explored different aspects of utilizing an exogenous surfactant as a drug delivery vehicle for glucocorticoids, such as budesonide [6,[11][12][13][14]. For example, numerous in vitro studies have characterized the successful incorporation of budesonide into exogenous surfactants, demonstrated their ability to transport budesonide across air-liquid interfaces, and even showcased their ability to improve the drug's anti-inflammatory effects at a distal site, without interfering with the biophysical function of surfactant [6,10,11]. In animal experiments, recent data have demonstrated that intratracheally instilling budesonide with an exogenous surfactant enhanced its biodistribution within the lung [13].…”

Section: Discussionmentioning

confidence: 99%

“…Exogenous surfactant is a complex mixture of lipids and specialized proteins, usually obtained from natural sources such as cows or pigs [5]. The endogenous material, produced by type II alveolar cells in the lung, has been well studied and serves a vital biophysical role in reducing surface tension, thereby stabilizing the alveoli during normal breathing [6,7]. The discovery of surfactant deficiency in preterm infants led to the development of exogenous surfactant therapy [8].…”

Section: Introductionmentioning

confidence: 99%

“…Similarly, in vivo studies, including those modeling ARDS, have observed improved drug distribution and anti-inflammatory effects for glucocorticoids delivered by a surfactant vehicle [12][13][14]. In addition, it has been shown that through these properties, exogenous surfactant can re-open collapsed airways, overcome regions of edema, and thereby efficiently spread to the deeper, more remote sites of inflammation even in an injured lung [6]. Together, this data highlights the potential for exogenous surfactant to provide these locally acting anti-inflammatory drugs' access to remote regions of the lung otherwise inaccessible to therapeutics.…”

Section: Introductionmentioning

confidence: 99%

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Exogenous Surfactant as a Pulmonary Delivery Vehicle for Budesonide In Vivo

Baer

McCaig

Yamashita

et al. 2020

Lung

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Exogenous Surfactant as a Pulmonary Delivery Vehicle for Budesonide In Vivo

Baer

McCaig

Yamashita

et al. 2020

Lung

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“…Another fundamental aspect of the therapy with surfactant which we should consider is that it is a carrier for the other drugs administered, facilitating, the delivery of a compound to the remote areas of the lung, so allowing the associated costicosteroids to reach them [6].…”

Section: Discussionmentioning

confidence: 99%

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2021

JAPM

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“…This group of antibiotics appears to be less toxic than previously reported [ 11 ], but there is still concern about their possible adverse effects on systemic administration. Therefore, topical administration, for example in the mixture with an exogenous surfactant as a carrier, enhances the delivery of these drugs to the deeper regions of the lung [ 12 ] and appears to be a suitable alternative. In mixture with a surfactant, it retains its bactericidal properties and reduces entry Escherichia coli ( E. coli ) from the alveolar space into the bloodstream in neonatal models of pneumonia [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

The Effect of Modified Porcine Surfactant Alone or in Combination with Polymyxin B on Lung Homeostasis in LPS-Challenged and Mechanically Ventilated Adult Rats

Kopincova

Nová

et al. 2020

Molecules

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The study aimed to prove the hypothesis that exogenous surfactant and an antibiotic polymyxin B (PxB) can more effectively reduce lipopolysaccharide (LPS)-induced acute lung injury (ALI) than surfactant treatment alone, and to evaluate the effect of this treatment on the gene expression of surfactant proteins (SPs). Anesthetized rats were intratracheally instilled with different doses of LPS to induce ALI. Animals with LPS 500 μg/kg have been treated with exogenous surfactant (poractant alfa, Curosurf®, 50 mg PL/kg b.w.) or surfactant with PxB 1% w.w. (PSUR + PxB) and mechanically ventilated for 5 hrs. LPS at 500 μg/kg increased lung edema, oxidative stress, and the levels of proinflammatory mediators in lung tissue and bronchoalveolar lavage fluid (BALF). PSUR reduced lung edema and oxidative stress in the lungs and IL-6 in BALF. This effect was further potentiated by PxB added to PSUR. Exogenous surfactant enhanced the gene expression of SP-A, SP-B, and SP-C, however, gene expression for all SPs was reduced after treatment with PSUR + PxB. In mechanically ventilated rats with LPS-induced ALI, the positive effect of exogenous surfactant on inflammation and oxidative stress was potentiated with PxB. Due to the tendency for reduced SPs gene expression after surfactant/PxB treatment topical use of PxB should be considered with caution.

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New insights into exogenous surfactant as a carrier of pulmonary therapeutics

Cited by 37 publications

References 102 publications

Exogenous Surfactant as a Pulmonary Delivery Vehicle for Budesonide In Vivo

Exogenous Surfactant as a Pulmonary Delivery Vehicle for Budesonide In Vivo

Untitled

The Effect of Modified Porcine Surfactant Alone or in Combination with Polymyxin B on Lung Homeostasis in LPS-Challenged and Mechanically Ventilated Adult Rats

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