{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T20:08:35Z","timestamp":1768680515174,"version":"3.49.0"},"reference-count":24,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T00:00:00Z","timestamp":1628726400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T00:00:00Z","timestamp":1628726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["INV-001227"],"award-info":[{"award-number":["INV-001227"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Inhalation of dry powder synthetic lung surfactant may assist spontaneous breathing by providing noninvasive surfactant therapy for premature infants supported with nasal continuous positive airway pressure. Surfactant was formulated using spray-drying with different phospholipid compositions (70 or 80 total weight% and 7:3 or 4:1 DPPC:POPG ratios), a surfactant protein B peptide analog (KL4, Super Mini-B, or B-YL), and Lactose or Trehalose as excipient. KL4 surfactant underperformed on initial adsorption and surface activity at captive bubble surfactometry. Spray-drying had no effect on the chemical composition of Super Mini-B and B-YL peptides and surfactant with these peptides had excellent surface activity with particle sizes and fine particle fractions that were well within the margins for respiratory particles and similar solid-state properties. Prolonged exposure of the dry powder surfactants with lactose as excipient to 40\u00a0\u00b0C and 75% humidity negatively affected hysteresis during dynamic cycling in the captive bubble surfactometer. Dry powder synthetic lung surfactants with 70% phospholipids (DPPC and POPG at a 7:3 ratio), 25% trehalose and 3% of SMB or B-YL showed excellent surface activity and good short-term stability, thereby qualifying them for potential clinical use in premature infants.<\/jats:p>","DOI":"10.1038\/s41598-021-95999-0","type":"journal-article","created":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T10:03:40Z","timestamp":1628762620000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Aerosol, chemical and physical properties of dry powder synthetic lung surfactant for noninvasive treatment of neonatal respiratory distress syndrome"],"prefix":"10.1038","volume":"11","author":[{"given":"Frans J.","family":"Walther","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Holly","family":"Chan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacob R.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mike","family":"Tauber","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan J.","family":"Waring","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,8,12]]},"reference":[{"key":"95999_CR1","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1542\/peds.2013-3443","volume":"133","author":"RA Polin","year":"2014","unstructured":"Polin, R. A., Carlo, W. A. & Committee on Fetus and Newborn & American Academy of Pediatrics. Surfactant replacement therapy for preterm and term neonates with respiratory distress. Pediatrics 133, 156\u2013163 (2014).","journal-title":"Pediatrics"},{"key":"95999_CR2","doi-asserted-by":"publisher","DOI":"10.1159\/000451076","author":"FJ Walther","year":"2016","unstructured":"Walther, F. J., Gordon, L. M. & Waring, A. J. Design of surfactant protein B peptide mimics based on the saposin fold for synthetic lung surfactants. Biomed. Hub. https:\/\/doi.org\/10.1159\/000451076 (2016).","journal-title":"Biomed. Hub."},{"key":"95999_CR3","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1126\/science.1948032","volume":"254","author":"CG Cochrane","year":"1991","unstructured":"Cochrane, C. G. & Revak, S. D. Pulmonary surfactant protein B (SP-B): Structure\u2013function relationships. Science 254, 566\u2013568 (1991).","journal-title":"Science"},{"issue":"39","key":"95999_CR4","doi-asserted-by":"publisher","first-page":"11047","DOI":"10.1021\/bi7011756","volume":"46","author":"M Sarker","year":"2007","unstructured":"Sarker, M., Waring, A. J., Walther, F. J., Keough, K. M. & Booth, V. Structure of mini-B, a functional fragment of surfactant protein B, in detergent micelles. Biochemistry 46(39), 11047\u201311056 (2007).","journal-title":"Biochemistry"},{"key":"95999_CR5","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0008672","volume":"5","author":"FJ Walther","year":"2010","unstructured":"Walther, F. J. et al. Critical structural and functional roles for the N-terminal insertion sequence in surfactant protein B analogs. PLoS ONE 5, e8672. https:\/\/doi.org\/10.1371\/journal.pone.0008672 (2010).","journal-title":"PLoS ONE"},{"key":"95999_CR6","doi-asserted-by":"publisher","first-page":"3113","DOI":"10.1016\/j.bbamem.2016.09.014","volume":"1858","author":"AJ Waring","year":"2016","unstructured":"Waring, A. J., Gupta, M., Gordon, L. M., Fujii, G. & Walther, F. J. Stability of an amphipathic helix-hairpin surfactant peptide in liposomes. Biochim. Biophys. Acta. 1858, 3113\u20133119 (2016).","journal-title":"Biochim. Biophys. Acta."},{"key":"95999_CR7","doi-asserted-by":"publisher","first-page":"13","DOI":"10.12688\/gatesopenres.12799.2","volume":"2","author":"FJ Walther","year":"2018","unstructured":"Walther, F. J. et al. A sulfur-free peptide mimic of surfactant protein B (B-YL) exhibits high in vitro and in vivo surface activities. Gates Open Res. 2, 13. https:\/\/doi.org\/10.12688\/gatesopenres.12799.2 (2018).","journal-title":"Gates Open Res."},{"key":"95999_CR8","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/0014-5793(96)00290-6","volume":"384","author":"M Gustafsson","year":"1996","unstructured":"Gustafsson, M., Vandenbussche, G., Curstedt, T., Ruysschaert, J. M. & Johansson, J. The 21-residue surfactant peptide (LysLeu4)4Lys(KL4) is a transmembrane alpha-helix with a mixed nonpolar\/polar surface. FEBS Lett. 384, 185\u2013188 (1996).","journal-title":"FEBS Lett."},{"key":"95999_CR9","doi-asserted-by":"publisher","first-page":"2055","DOI":"10.1152\/japplphysiol.00153.2003","volume":"95","author":"J Johansson","year":"2003","unstructured":"Johansson, J. et al. A synthetic surfactant based on a poly-Leu SP-C analog and phospholipids: effects on tidal volumes and lung gas volumes in ventilated immature newborn rabbits. J. Appl. Physiol. 95, 2055\u20132063 (2003).","journal-title":"J. Appl. Physiol."},{"key":"95999_CR10","doi-asserted-by":"publisher","first-page":"e485","DOI":"10.7717\/peerj.485","volume":"2","author":"FJ Walther","year":"2014","unstructured":"Walther, F. J. et al. Surfactant protein C peptides with salt-bridges (\u201cion-locks\u201d) promote high surfactant activities by mimicking the \u03b1-helix and membrane topography of the native protein. PeerJ 2, e485. https:\/\/doi.org\/10.7717\/peerj.485 (2014).","journal-title":"PeerJ"},{"key":"95999_CR11","doi-asserted-by":"publisher","first-page":"1860","DOI":"10.1172\/JCI117173","volume":"93","author":"LM Nogee","year":"1994","unstructured":"Nogee, L. M. et al. A mutation in the surfactant protein B gene responsible for fatal neonatal respiratory disease in multiple kindreds. J. Clin. Invest. 93, 1860\u20131863 (1994).","journal-title":"J. Clin. Invest."},{"key":"95999_CR12","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/0005-2736(92)90292-T","volume":"1110","author":"MA Oosterlaken-Dijksterhuis","year":"1992","unstructured":"Oosterlaken-Dijksterhuis, M. A., van Eijk, M., van Golde, L. M. G. & Haagsman, H. P. Lipid mixing is mediated by the hydrophobic surfactant protein SP-B but not by SP-C. Biochim. Biophys. Acta. 1110, 45\u201350 (1992).","journal-title":"Biochim. Biophys. Acta."},{"key":"95999_CR13","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1016\/j.jmr.2006.10.006","volume":"184","author":"M Tang","year":"2007","unstructured":"Tang, M., Waring, A. J. & Hong, M. Trehalose-protected lipid membranes for determining membrane protein structure and insertion. J. Magn. Reson. 184, 222\u2013227 (2007).","journal-title":"J. Magn. Reson."},{"key":"95999_CR14","doi-asserted-by":"publisher","first-page":"6","DOI":"10.12688\/gatesopenres.12899.2","volume":"3","author":"FJ Walther","year":"2019","unstructured":"Walther, F. J. et al. Aerosol delivery of dry powder synthetic lung surfactant to surfactant-deficient rabbits and preterm lambs on non-invasive respiratory support. Gates Open Res. 3, 6. https:\/\/doi.org\/10.12688\/gatesopenres.12899.2 (2019).","journal-title":"Gates Open Res."},{"key":"95999_CR15","doi-asserted-by":"publisher","first-page":"2957","DOI":"10.1016\/j.bpj.2011.10.050","volume":"101","author":"N Holten-Andersen","year":"2011","unstructured":"Holten-Andersen, N. et al. KL4 peptide induces reversible collapse structures on multiple length scales in model lung surfactant. Biophys. J. 101, 2957\u20132965 (2011).","journal-title":"Biophys. J."},{"key":"95999_CR16","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1016\/S0925-4439(98)00067-2","volume":"1408","author":"S Sch\u00fcrch","year":"1998","unstructured":"Sch\u00fcrch, S., Green, F. H. & Bachofen, H. Formation and structure of surface films: Captive bubble surfactometry. Biochim. Biophys. Acta. 1408, 180\u2013202 (1998).","journal-title":"Biochim. Biophys. Acta."},{"key":"95999_CR17","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/0304-4165(94)90169-4","volume":"1200","author":"WM Schoel","year":"1994","unstructured":"Schoel, W. M., Sch\u00fcrch, S. & Goerke, J. The captive bubble method for the evaluation of pulmonary surfactant: Surface tension, area, and volume calculations. Biochim. Biophys. Acta. 1200, 281\u2013290 (1994).","journal-title":"Biochim. Biophys. Acta."},{"key":"95999_CR18","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/S1095-6433(01)00316-6","volume":"129","author":"S Sch\u00fcrch","year":"2001","unstructured":"Sch\u00fcrch, S., Bachofen, H. & Possmayer, F. Surface activity in situ, in vivo, and in the captive bubble surfactometer. Comp. Biochem. Physiol. A. 129, 195\u2013207 (2001).","journal-title":"Comp. Biochem. Physiol. A."},{"key":"95999_CR19","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1002\/cjce.5450580203","volume":"58","author":"JD Malcolm","year":"1980","unstructured":"Malcolm, J. D. & Elliot, C. D. Interfacial tension from height and diameter of a single profile drop or captive bubble. Can. J. Chem. Eng. 58, 151\u2013153 (1980).","journal-title":"Can. J. Chem. Eng."},{"key":"95999_CR20","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/S0140-6736(81)90002-7","volume":"1","author":"CJ Morley","year":"1981","unstructured":"Morley, C. J., Bangham, A. D., Miller, N. & Davis, J. A. Dry artificial lung surfactant and its effect on very premature babies. Lancet 1, 64\u201368 (1981).","journal-title":"Lancet"},{"key":"95999_CR21","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1080\/17476348.2019.1589372","volume":"13","author":"FJ Walther","year":"2019","unstructured":"Walther, F. J., Gordon, L. M. & Waring, A. J. Advances in synthetic lung surfactant protein technology. Expert Rev. Respir. Med. 13, 499\u2013501 (2019).","journal-title":"Expert Rev. Respir. Med."},{"key":"95999_CR22","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1208\/s12249-021-02001-1","volume":"22","author":"S Boc","year":"2021","unstructured":"Boc, S., Momin, M. A. M., Farkas, D. R., Longest, W. & Hindle, M. Development and characterization of excipient enhanced growth (EEG) surfactant powder formulations for treating neonatal respiratory distress syndrome. AAPS Pharm. Sci. Technol. 22, 136. https:\/\/doi.org\/10.1208\/s12249-021-02001-1 (2021).","journal-title":"AAPS Pharm. Sci. Technol."},{"key":"95999_CR23","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1186\/s12931-019-1096-9","volume":"20","author":"F Bianco","year":"2019","unstructured":"Bianco, F. et al. From bench to bedside: In vitro and in vivo evaluation of a neonate-focused nebulized surfactant delivery strategy. Respir. Res. 20, 134. https:\/\/doi.org\/10.1186\/s12931-019-1096-9 (2019).","journal-title":"Respir. Res."},{"key":"95999_CR24","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.403","volume":"2","author":"FJ Walther","year":"2014","unstructured":"Walther, F. J., Hern\u00e1ndez-Juviel, J. M. & Waring, A. J. Aerosol delivery of synthetic lung surfactant. PeerJ 2, e403. https:\/\/doi.org\/10.7717\/peerj.403 (2014).","journal-title":"PeerJ"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-95999-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-95999-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-95999-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T12:25:12Z","timestamp":1670070312000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-95999-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,12]]},"references-count":24,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["95999"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-95999-0","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,12]]},"assertion":[{"value":"20 May 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 August 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 August 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"16439"}}