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Here, we report a biomimetic platform based on pulmonary surfactant nanoparticles (PS\n                    <jats:sub>NPs<\/jats:sub>\n                    ) that preserves native surfactant proteins and biophysical functionality, resulting in enhanced pulmonary delivery. Microfluidic synthesis yielded highly uniform PS\n                    <jats:sub>NPs<\/jats:sub>\n                    with improved encapsulation efficiency and colloidal stability, while markedly increasing surfactant protein retention from 33% using conventional extrusion to 95% via microfluidics, corresponding to a 2.4\u2010fold improvement. Functionally, PS\n                    <jats:sub>NPs<\/jats:sub>\n                    exhibited superior interfacial activity compared to lipid\u2010only liposomes, increasing surface pressure from 5\u201310 mN\/m to 25\u201330 mN\/m, and achieved an approximately 80\u2010fold enhancement in alveolar cellular uptake. In vitro, nintedanib\u2010loaded PS\n                    <jats:sub>NPs<\/jats:sub>\n                    significantly reduced fibroblast migration, proliferation, collagen deposition, and TGF\u2010\u03b2 secretion relative to free drug and control formulations. In vivo, PS\n                    <jats:sub>NPs<\/jats:sub>\n                    demonstrated high pulmonary retention (95% injected dose per gram of lung tissue), efficient penetration into fibrotic regions, and minimal off\u2010target accumulation in the liver (0.5%). Therapeutic efficacy was confirmed in a bleomycin\u2010induced pulmonary fibrosis model, where PS\n                    <jats:sub>NPs<\/jats:sub>\n                    improved lung function and restored tissue architecture at doses as low as 0.5\u00a0mg\/kg. Collectively, these results establish PS\n                    <jats:sub>NPs<\/jats:sub>\n                    as a robust lung\u2010targeted nanotherapeutic platform, where microfluidic synthesis enables enhanced biomimicry, improved protein preservation, and superior therapeutic performance compared to conventional fabrication methods.\n                  <\/jats:p>","DOI":"10.1002\/adhm.202505871","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T04:37:34Z","timestamp":1779251854000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pulmonary Surfactant Nanoparticles for Lung\u2010Targeted and Dose\u2010Efficient Delivery"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8783-2330","authenticated-orcid":false,"given":"Laura","family":"Fern\u00e1ndez\u2010M\u00e9ndez","sequence":"first","affiliation":[{"name":"Center for Cooperative Research in 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