Pulmonary surfactant and drug delivery: Vehiculization, release and targeting of surfactant/tacrolimus formulations

An adverse outcome pathway for lung surfactant function inhibition leading to decreased lung function

“…It is a pre-requisite that the aerodynamic diameter of the inhaled substance is less than 4 µm in order to enter the alveoli, where the lung surfactant is located ( ISO, ISO 7708:, 1995 ). Another way to interact with the lung surfactant is to travel from the upper airways to the alveoli via diffusion, which can be facilitated upon association with the air–liquid interface ( Hidalgo et al, 2021 ).…”

Pulmonary Surfactant and Drug Delivery: An Interface-Assisted Carrier to Deliver Surfactant Protein SP-D Into the Airways

“…In the study, we have used a recombinant form of human SP-D. Our experiments are therefore also useful to show how the combination of the protein with PS could be a useful strategy to facilitate an efficient delivery of the protein through the airways as a therapeutic option, using PS as a shuttle. The use of PS as a drug delivery system to carry and distribute different therapeutic molecules over the respiratory surfaces have been studied in the recent years both in vitro and in vivo (Van't Veen et al, 1996;Hidalgo et al, 2017Hidalgo et al, , 2020Baer et al, 2018). The combination of exogenous PS with rhSP-D could have the potential to serve as a preventive or therapeutic approach to treat inflammatory responses and lung diseases in preterm infants such as RDS or bronchopulmonary dysplasia (BPD) (Ikegami et al, 2007;Sato et al, 2010).…”

“…However, the absence of breathing-like interfacial compression/expansion dynamics in the current experiments could limit the behavior of SP-D compared with the potential action of the protein in vivo. We have recently demonstrated that breathing dynamics could be essential to understand the interfacial behavior of surfactant, particularly with respect to potential interface-assisted spreading capabilities and release processes (Hidalgo et al, 2020), as a consequence of surface tension-driven interfacial flows and the potential progressive exclusion of material from the interface (Borgas and Grotberg, 1988;Pastrana-Rios et al, 1994;Grotberg and Gaver III, 1996;Halpern et al, 1998;Keating et al, 2012;Hidalgo et al, 2020). These effects could be important to promote the spreading of new material coming from upstream reservoirs and better distribute the therapeutics over the respiratory surface (Hidalgo et al, 2020).…”

“…PS enables the process of breathing by lowering the surface tension of the layer of water covering the whole respiratory surface, minimizing the work of breathing and avoiding the alveolar collapse. Apart from the interfacial and immune defense functions, its composition and interfacial properties confers PS the possibility to spread efficiently over air-liquid interfaces and transport therapeutic molecules by surfing the respiratory surface, what has been called an interfacial delivery (Hidalgo et al, 2020).…”

Pulmonary surfactant as a versatile biomaterial to fight COVID-19

“…However, the availability of both preventive measures as well as (combination) therapies for already infected patients might be most effective. Therefore, in response to the urgency to fight the escalating COVID-19 pandemic, many existing drugs have been screened with the aim to identify compounds that could be successfully repurposed, since such an approach is more time- and cost efficient and is correlated to higher success rates compared to the development of novel anti-SARS-CoV-2 drugs [ [7] , [8] , [9] , [10] ]. A variety of compounds from diverse drug classes including antivirals ( e.g.…”