This work is focused on the potential use of pulmonary surfactant to deliver full-length recombinant human surfactant protein SP-D (rhSP-D) using the respiratory air-liquid interface as a shuttle. Surfactant protein D (SP-D) is a collectin protein present in the pulmonary surfactant (PS) system, involved in innate immune defense and surfactant homeostasis. It has been recently suggested as a potential therapeutic to alleviate inflammatory responses and lung diseases in preterm infants suffering from respiratory distress syndrome (RDS) or bronchopulmonary dysplasia (BPD). However, none of the current clinical surfactants used for surfactant replacement therapy (SRT) to treat RDS contain SP-D. The interaction of SP-D with surfactant components, the potential of PS as a respiratory drug delivery system and the possibility to produce recombinant versions of human SP-D, brings the possibility of delivering clinical surfactants supplemented with SP-D. Here, we used an in vitro setup that somehow emulates the respiratory air-liquid interface to explore this novel approach. It consists in two different compartments connected with a hydrated paper bridge forming a continuous interface. We firstly analyzed the adsorption and spreading of rhSP-D alone from one compartment to another over the air-liquid interface, observing low interfacial activity. Then, we studied the interfacial spreading of the protein co-administered with PS, both at different time periods or as a mixed formulation, and which oligomeric forms of rhSP-D better traveled associated with PS. The results presented here demonstrated that PS may transport rhSP-D long distances over air-liquid interfaces, either as a mixed formulation or separately in a close window time, opening the doors to empower the current clinical surfactants and SRT.
Publication Summary:
- The study investigates the efficacy of using pulmonary surfactant (PS) to facilitate an efficient delivery of Airway’s novel recombinant human protein AT-100 (rhSP-D) as a therapeutic option.
- AT-100 is under investigation as a potential therapy to treat respiratory and inflammatory diseases in preterm infants, such as bronchopulmonary dysplasia.
- In vitro experiments using a mimic of the respiratory air-liquid interface demonstrate enhanced adsorption and distribution of rhSP-D in the presence of PS.
- Results demonstrate that PS may serve as an adequate delivery and administration vehicle for rhSP-D for the treatment of diseases associated with lung infection and inflammatory syndromes.
García-Mouton et al.
Frontiers in Bioengineering and Biotechnology
