{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T02:20:20Z","timestamp":1788142820439,"version":"build-2803163510"},"reference-count":49,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T00:00:00Z","timestamp":1788048000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: The recent advances in pulmonary delivery have shifted the paradigm to the development of inhalable drug-loaded polysaccharide particles that can be positioned at the respiratory interface while reducing the systemic exposure. Quercetin has broad anticancer activity but remains difficult to translate because of its poor aqueous solubility, limited bioavailability and rapid metabolic loss. Here, we report quercetin-loaded chitosan\/Salvia hispanica polysaccharide nanoparticles as a natural polyelectrolyte nanocarrier for pulmonary delivery in lung cancer. Methods: Central composite design (CCD) and artificial neural network (ANN) models were used for mapping the factors to responses. Results: The models displayed a higher predictive accuracy and optimization reliability for identifying the optimized formulation. The optimized nanoparticles showed a quasi-spherical morphology (mean hydrodynamic diameter = 331 \u00b1 14.34 nm) with cationic \u03b6-potential of +36.3 \u00b1 2.56 mV and polydispersity index of 0.15. The optimized formulation showed acceptable powder-flow characteristics, an encapsulation efficiency of 73.8 \u00b1 0.73%, drug loading of 14.20 \u00b1 0.22%, and biphasic release with sustained quercetin release over 48 h. In A549 and H460 cell lines, nanoencapsulation increased the antiproliferative effect of quercetin relative to the free compound, yielding lower IC50 values after 48 h of exposure. The nanoparticles showed greater suppression of wound closure, increased reactive oxygen species fluorescence and clear cellular uptake. Blank nanoparticles produced only limited effects. Conclusions: These results indicate that CCD\/ANN-guided chitosan\/Salvia hispanica polysaccharide nanoparticles provide a promising nanodelivery tool for quercetin delivery and enhanced in vitro activity in lung cancer cells, while the observed aerosol performance advocates further investigation of their pulmonary delivery potential.<\/jats:p>","DOI":"10.3390\/pharmaceutics18091095","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T02:08:58Z","timestamp":1788142138000},"page":"1095","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Aerosolized Quercetin-Loaded Chia Seed Polysaccharide Nanoparticles: Design of Experiments and Machine-Learning-Guided Optimization for Enhanced Lung Cancer Cell Delivery"],"prefix":"10.3390","volume":"18","author":[{"given":"Sara","family":"Hasan","sequence":"first","affiliation":[{"name":"School of Chemistry and Physics, Queensland University of Technology (QUT), Brisbane, QLD 4000, Australia"},{"name":"Centre for Materials Science, Queensland University of Technology (QUT), 2 George Street, Brisbane, QLD 4000, Australia"},{"name":"Cancer & Ageing Research Program, Centre for Genomics and Personalised Health, Queensland University of Technology (QUT), 60 Musk Ave, Brisbane, QLD 4059, Australia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4000-3498","authenticated-orcid":false,"given":"Seyedeh Negin","family":"Kassaee","sequence":"additional","affiliation":[{"name":"Pharmacy Discipline, School of Clinical Sciences, Faculty of Health, Queensland University of Technology (QUT), Brisbane, QLD 4000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Derek J.","family":"Richard","sequence":"additional","affiliation":[{"name":"Cancer & Ageing Research Program, Centre for Genomics and Personalised Health, Queensland University of Technology (QUT), 60 Musk Ave, Brisbane, QLD 4059, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6751-6915","authenticated-orcid":false,"given":"Nazrul","family":"Islam","sequence":"additional","affiliation":[{"name":"Pharmacy Discipline, School of Clinical Sciences, Faculty of Health, Queensland University of Technology (QUT), Brisbane, QLD 4000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1353-6827","authenticated-orcid":false,"given":"Emad L.","family":"Izake","sequence":"additional","affiliation":[{"name":"School of Chemistry and Physics, Queensland University of Technology (QUT), Brisbane, QLD 4000, Australia"},{"name":"Centre for Materials Science, Queensland University of Technology (QUT), 2 George Street, Brisbane, QLD 4000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"conceptualization","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,30]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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