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Moritz Beck-Broichsitter
Colloidal drug carriers could improve the therapy of numerous airway diseases. However, it remains unclear to what extent nanoscale particulate matter affects the biophysical function of the essential surface-active lining layer of the lungs, especially under predisposed conditions of airway diseases. Accordingly, the current study investigated the impact of defined polymer nanoparticles on impaired lung surfactants. Admixtures of plasma proteins (albumin and fibrinogen) to Curosurf led to a controllable decrease in surface activity (i...
October 11, 2016: Langmuir: the ACS Journal of Surfaces and Colloids
Ioannis G Theodorou, Pakatip Ruenraroengsak, Andrew Gow, Stephan Schwander, Junfeng Jim Zhang, Kian Fan Chung, Teresa D Tetley, Mary P Ryan, Alexandra E Porter
Inhaled nanoparticles (NPs) have high-deposition rates in the alveolar region of the lung but the effects of pulmonary surfactant (PS) on nanoparticle bioreactivity are unclear. Here, the impact of PS on the stability and dissolution of ZnO nanowires (ZnONWs) was investigated, and linked with their bioreactivity in vitro with human alveolar epithelial type 1-like cells (TT1). Pre-incubation of ZnONWs with Curosurf® (a natural porcine PS) decreased their dissolution at acidic pH, through the formation of a phospholipid corona...
November 2016: Nanotoxicology
P Mikolka, J Kopincova, L Tomcikova Mikusiakova, P Kosutova, A Calkovska, D Mokra
Neonatal meconium aspiration syndrome (MAS) can be treated by exogenous surfactant (S). However, aspirated meconium initiates local inflammation and oxidation which may inactivate surfactant and reduce its action. This experimental study estimated whether combined use of surfactant and the antioxidant N-acetylcysteine (NAC) can enhance effectiveness of therapy. Meconium-instilled rabbits were non-treated (M), treated with monotherapies (M + S, M + NAC), combined therapy (M + S + NAC), or received saline instead of meconium (controls, C)...
2016: Advances in Experimental Medicine and Biology
Sinbad Sweeney, Bey Fen Leo, Shu Chen, Nisha Abraham-Thomas, Andrew J Thorley, Andrew Gow, Stephan Schwander, Junfeng Jim Zhang, Milo S P Shaffer, Kian Fan Chung, Mary P Ryan, Alexandra E Porter, Teresa D Tetley
Accompanying increased commercial applications and production of silver nanomaterials is an increased probability of human exposure, with inhalation a key route. Nanomaterials that deposit in the pulmonary alveolar region following inhalation will interact firstly with pulmonary surfactant before they interact with the alveolar epithelium. It is therefore critical to understand the effects of human pulmonary surfactant when evaluating the inhalation toxicity of silver nanoparticles. In this study, we evaluated the toxicity of AgNPs on human alveolar type-I-like epithelial (TT1) cells in the absence and presence of Curosurf(®) (a natural pulmonary surfactant substitute), hypothesising that the pulmonary surfactant would act to modify toxicity...
September 1, 2016: Colloids and Surfaces. B, Biointerfaces
Markus Fehrholz, Kirsten Glaser, Silvia Seidenspinner, Barbara Ottensmeier, Tore Curstedt, Christian P Speer, Steffen Kunzmann
BACKGROUND: Natural surfactant preparations, commonly isolated from porcine or bovine lungs, are used to treat respiratory distress syndrome in preterm infants. Besides biophysical effectiveness, several studies have documented additional immunomodulatory properties. Within the near future, synthetic surfactant preparations may be a promising alternative. CHF5633 is a new generation reconstituted synthetic surfactant preparation with defined composition, containing dipalmitoyl-phosphatidylcholine, palmitoyl-oleoyl-phosphatidylglycerol and synthetic analogs of surfactant protein (SP-) B and SP-C...
2016: PloS One
P Mikolka, J Kopincova, L Tomcikova Mikusiakova, P Kosutova, M Antosova, A Calkovska, D Mokra
Meconium aspiration syndrome (MAS) is a serious condition, which can be treated with exogenous surfactant and mechanical ventilation. However, meconium-induced inflammation, lung edema and oxidative damage may inactivate delivered surfactant and thereby reduce effectiveness of the therapy. As we presumed that addition of anti-inflammatory agent into the surfactant may alleviate inflammation and enhance efficiency of the therapy, this study was performed to evaluate effects of surfactant therapy enriched with budesonide versus surfactant-only therapy on markers of oxidative stress in experimental model of MAS...
February 2016: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
Wendel Wohlleben, Marc D Driessen, Simon Raesch, Ulrich F Schaefer, Christine Schulze, Bernhard von Vacano, Antje Vennemann, Martin Wiemann, Christian A Ruge, Herbert Platsch, Sarah Mues, Rainer Ossig, Janina M Tomm, Jürgen Schnekenburger, Thomas A J Kuhlbusch, Andreas Luch, Claus-Michael Lehr, Andrea Haase
Lung lining fluid is the first biological barrier nanoparticles (NPs) encounter during inhalation. As previous inhalation studies revealed considerable differences between surface functionalized NPs with respect to deposition and toxicity, our aim was to investigate the influence of lipid and/or protein binding on these processes. Thus, we analyzed a set of surface functionalized NPs including different SiO2 and ZrO2 in pure phospholipids, CuroSurf(TM) and purified native porcine pulmonary surfactant (nS). Lipid binding was surprisingly low for pure phospholipids and only few NPs attracted a minimal lipid corona...
September 2016: Nanotoxicology
Ilaria Milesi, David G Tingay, Emanuela Zannin, Federico Bianco, Paolo Tagliabue, Fabio Mosca, Anna Lavizzari, Maria Luisa Ventura, C Elroy Zonneveld, Elizabeth J Perkins, Don Black, Magdy Sourial, Raffaele L Dellacá
BACKGROUND: Aerosolization of exogenous surfactant remains a challenge. This study is aimed to evaluate the efficacy of atomized poractant alfa (Curosurf) administered with a novel atomizer in preterm lambs with respiratory distress syndrome. METHODS: Twenty anaesthetized lambs, 127 ± 1 d gestational age, (mean ± SD) were instrumented before birth and randomized to receive either (i) positive pressure ventilation without surfactant (Control group), (ii) 200 mg/kg of bolus instilled surfactant (Bolus group) at 10 min of life or (iii) 200 mg/kg of atomized surfactant (Atomizer group) over 60 min from 10 min of life...
July 2016: Pediatric Research
Zeeshan H Syedain, Amir A Naqwi, Myrna Dolovich, Arif Somani
For infants born with respiratory distress syndrome (RDS), liquid bolus delivery of surfactant administered through an endotracheal tube is common practice. While this method is generally effective, complications such as transient hypoxia, hypercapnia, and altered cerebral blood flow may occur. Aerosolized surfactant therapy has been explored as an alternative. Unfortunately, past efforts have led to disappointing results as aerosols were generated outside the lungs with significant pharyngeal deposition and minimal intrapulmonary instillation...
September 1, 2015: Aerosol Science and Technology: the Journal of the American Association for Aerosol Research
Kirsten Glaser, Markus Fehrholz, Tore Curstedt, Steffen Kunzmann, Christian P Speer
BACKGROUND: Surfactant replacement therapy is the standard of care for the prevention and treatment of neonatal respiratory distress syndrome. New generation synthetic surfactants represent a promising alternative to animal-derived surfactants. CHF5633, a new generation reconstituted synthetic surfactant containing SP-B and SP-C analogs and two synthetic phospholipids has demonstrated biophysical effectiveness in vitro and in vivo. While several surfactant preparations have previously been ascribed immunomodulatory capacities, in vitro data on immunomodulation by CHF5633 are limited, so far...
2016: PloS One
Andrea Calkovska, Bim Linderholm, Marie Haegerstrand-Björkman, Barbara Pioselli, Nicola Pelizzi, Jan Johansson, Tore Curstedt
BACKGROUND: The development of synthetic surfactants for the treatment of lung pulmonary diseases has been going on for many years. OBJECTIVES: To investigate the effects of phospholipid mixtures combined with SP-B and SP-C analogues on lung functions in an animal model of respiratory distress syndrome. METHODS: Natural and synthetic phospholipid mixtures with/without SP-B and/or SP-C analogues were instilled in ventilated premature newborn rabbits...
2016: Neonatology
Matthias C Hütten, Elke Kuypers, Daan R Ophelders, Maria Nikiforou, Reint K Jellema, Hendrik J Niemarkt, Carola Fuchs, Markus Tservistas, Roberta Razetti, Federico Bianco, Boris W Kramer
BACKGROUND: Surfactant replacement therapy is the gold standard treatment of neonatal respiratory distress (RDS). Nebulization is a noninvasive mode of surfactant administration. We administered Poractant alfa (Curosurf) via a vibrating perforated membrane nebulizer (eFlow Neonatal Nebulizer) to spontaneously breathing preterm lambs during binasal continuous positive pressure ventilation (CPAP). METHODS: Sixteen preterm lambs were operatively delivered at a gestational age of 133 ± 1 d (term ~150 d), and connected to CPAP applied via customized nasal prongs...
December 2015: Pediatric Research
Eline Hermans, M Saad Bhamla, Peter Kao, Gerald G Fuller, Jan Vermant
The surfactant lining the walls of the alveoli in the lungs increases pulmonary compliance and prevents collapse of the lung at the end of expiration. In premature born infants, surfactant deficiency causes problems, and lung surfactant replacements are instilled to facilitate breathing. These pulmonary surfactants, which form complex structured fluid-fluid interfaces, need to spread with great efficiency and once in the alveolus they have to form a thin stable film. In the present work, we investigate the mechanisms affecting the stability of surfactant-laden thin films during spreading, using drainage flows from a hemispherical dome...
November 7, 2015: Soft Matter
Liang Zhang, Hong-Yi Cao, Shuang Zhao, Li-Jie Yuan, Dan Han, Hong Jiang, Song Wu, Hong-Min Wu
BACKGROUND: The utilization of multiple natural and synthetic products in surfactant replacement therapies in treatment of neonatal respiratory distress syndrome (NRDS) prompted us to take a closer looks at these various therapeutic options and their efficacies. The purpose of our study was to evaluate the effects of six exogenous pulmonary surfactants (EPS) (Survanta, Alveofact, Infasurf, Curosurf, Surfaxin and Exosurf) on mortality rate in NRDS by a network meta-analysis. METHODS: An exhaustive search of electronic databases was performed in PubMed, Ovid, EBSCO, Springerlink, Wiley, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang and VIP databases (last updated search in October 2014) to retrieve randomized controlled trials (RCTs) relevant to our study topic...
October 2015: Pulmonary Pharmacology & Therapeutics
F Mousseau, R Le Borgne, E Seyrek, J-F Berret
We report on the interaction of pulmonary surfactant composed of phospholipids and proteins with nanometric alumina (Al2O3) in the context of lung exposure and nanotoxicity. We study the bulk properties of phospholipid/nanoparticle dispersions and determine the nature of their interactions. The clinical surfactant Curosurf, both native and extruded, and a protein-free surfactant are investigated. The phase behavior of mixed surfactant/particle dispersions was determined by optical and electron microscopy, light scattering, and zeta potential measurements...
July 7, 2015: Langmuir: the ACS Journal of Surfaces and Colloids
Ioannis G Theodorou, Danielle Botelho, Stephan Schwander, Junfeng Zhang, Kian Fan Chung, Teresa D Tetley, Milo S P Shaffer, Andrew Gow, Mary P Ryan, Alexandra E Porter
The increase of production volumes of silver nanowires (AgNWs) and of consumer products incorporating them may lead to increased health risks from occupational and public exposures. There is currently limited information about the putative toxicity of AgNWs upon inhalation and incomplete understanding of the properties that control their bioreactivity. The lung lining fluid (LLF), which contains phospholipids and surfactant proteins, represents a first contact site with the respiratory system. In this work, the impact of dipalmitoylphosphatidylcholine (DPPC), Curosurf, and murine LLF on the stability of AgNWs was examined...
July 7, 2015: Environmental Science & Technology
Tore Curstedt, Henry L Halliday, Christian P Speer
Surfactant deficiency was identified as the cause of respiratory distress syndrome (RDS) as long ago as 1959. Trials of surfactant replacement in the 1960s were unsuccessful because the preparations used contained only phospholipids and they were administered inefficiently by nebulization. In the 1970s Bengt Robertson and Göran Enhörning showed that natural surfactant, containing both phospholipids and proteins, could ameliorate the signs of RDS in immature rabbits. In the 1980s Bengt Robertson and Tore Curstedt developed a porcine surfactant, Curosurf (named after their surnames), which was effective in immature animals and was used in a pilot clinical trial beginning in 1983...
2015: Neonatology
Sinbad Sweeney, Ioannis G Theodorou, Marta Zambianchi, Shu Chen, Andrew Gow, Stephan Schwander, Junfeng Jim Zhang, Kian Fan Chung, Milo S P Shaffer, Mary P Ryan, Alexandra E Porter, Teresa D Tetley
Inhaled nanoparticles have a high deposition rate in the alveolar units of the deep lung. The alveolar epithelium is composed of type-I and type-II epithelial cells (ATI and ATII respectively) and is bathed in pulmonary surfactant. The effect of native human ATII cell secretions on nanoparticle toxicity is not known. We investigated the cellular uptake and toxicity of silver nanowires (AgNWs; 70 nm diameter, 1.5 μm length) with human ATI-like cells (TT1), in the absence or presence of Curosurf® (a natural porcine pulmonary surfactant with a low amount of protein) or harvested primary human ATII cell secretions (HAS; containing both the complete lipid as well as the full protein complement of human pulmonary surfactant i...
June 21, 2015: Nanoscale
Lynn De Backer, Kevin Braeckmans, Marc C A Stuart, Jo Demeester, Stefaan C De Smedt, Koen Raemdonck
Inhalation therapy with small interfering RNA (siRNA) is a promising approach in the treatment of pulmonary disorders. However, clinical translation is severely limited by the lack of suitable delivery platforms. In this study, we aim to address this limitation by designing a novel bioinspired hybrid nanoparticle with a core-shell nanoarchitecture, consisting of a siRNA-loaded dextran nanogel (siNG) core and a pulmonary surfactant (Curosurf®) outer shell. The decoration of siNGs with a surfactant shell enhances the colloidal stability and prevents siRNA release in the presence of competing polyanions, which are abundantly present in biofluids...
May 28, 2015: Journal of Controlled Release: Official Journal of the Controlled Release Society
Celso Moura Rebello, Alexander Roberto Precioso, Renata Suman Mascaretti
OBJECTIVE: To compare the efficacy and safety of a new porcine-derived pulmonary surfactant developed by Instituto Butantan with those of animal-derived surfactants commercially available in Brazil, regarding neonatal mortality and the major complications of prematurity in preterm newborns with birth weight up to 1500g and diagnosed with respiratory distress syndrome. METHODS: Neonates diagnosed with respiratory distress syndrome were randomized to receive either Butantan surfactant (Butantan group) or one of the following surfactants: Survanta® or Curosurf®...
October 2014: Einstein
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