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Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, has beenrepurposed as an anticancer agent for NSCLC therapy. In the present study, celecoxib-loaded Soluplus\/zein composite nanoparticles coated with chitosan were successfully developed and evaluated as a promising pulmonary drug delivery system for NSCLC. The nanoparticles were prepared using an antisolvent precipitation technique and demonstrated favorable physicochemical properties. The optimized formulation exhibited a particle size of approximately 190 nm with high encapsulation efficiency (85.34%), and high drug-loading capacity (14.21%). The chitosan coating increased the zeta potential to nearly +30.42 mV, yielding enhanced stability and desirable mucoadhesive properties for pulmonary administration. In vitro release studies revealed sustained release under simulated physiological lung conditions, following diffusion- and swelling-controlled release mechanisms. Cytotoxicity evaluation using the MTT assay demonstrated significant anticancer activity against A549 lung cancer cells while maintaining good biocompatibility toward BEAS-2B normal human bronchial epithelial cells. The optimized nanoparticles also showed efficient transport across an air\u2013liquid interface (ALI) airway epithelial barrier, with a Papp value of 4.15 \u00d7 10\u20134 cm\u00b7s\u20131 and 0.38% translocation after 24 h. Furthermore, aerosolized nanoparticles displayed excellent aerodynamic performance, with a fine particle fraction (FPF) of 68.51% and a mass median aerodynamic diameter (MMAD) of 3.93 \u03bcm using the Next Generation Impactor (NGI). Overall, these findings highlight the potential of celecoxib-loaded Soluplus\/zein nanoparticles coated with chitosan as a promising pulmonary drug delivery system for NSCLC via nebulization.<\/jats:p>","DOI":"10.1021\/acsomega.6c07052","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T09:01:55Z","timestamp":1786352515000},"page":"50499-50516","source":"Crossref","is-referenced-by-count":1,"title":["Development and\nCharacterization of Celecoxib-Loaded Soluplus\/Zein Composite Nanoparticles\nCoated with Chitosan for Pulmonary Drug Delivery"],"prefix":"10.1021","volume":"11","author":[{"given":"Khin Cho","family":"Nyein","sequence":"first","affiliation":[{"name":"Chulalongkorn University , , ,","place":["Bangkok, Thailand, 10330"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maxius","family":"Gunawan","sequence":"additional","affiliation":[{"name":"Chulalongkorn University , , ,","place":["Bangkok, Thailand, 10330"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0595-982X","authenticated-orcid":true,"given":"Papon","family":"Muangsanit","sequence":"additional","affiliation":[{"name":"National Science and Technology Development Agency (NSTDA) , , ,","place":["Pathumthani, Thailand, 12120"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudartip","family":"Areecheewakul","sequence":"additional","affiliation":[{"name":"Chulalongkorn University , , ,","place":["Bangkok, Thailand, 10330"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jittima","family":"Chatchawalsaisin","sequence":"additional","affiliation":[{"name":"Chulalongkorn University , , ,","place":["Bangkok, Thailand, 10330"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2541-9201","authenticated-orcid":true,"given":"Nattika","family":"Nimmano","sequence":"additional","affiliation":[{"name":"Chulalongkorn University , , ,","place":["Bangkok, Thailand, 10330"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,10]]},"reference":[{"issue":"1","key":"2026083119131396300_cit1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/nrdp.2015.9","article-title":"Non-small-cell lung\ncancer","volume":"1","author":"Gridelli","year":"2015","journal-title":"Nat. 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