{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T04:46:14Z","timestamp":1785732374828,"version":"3.56.0"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007414","name":"Qassim University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007414","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    Pulmonary fibrosis (PF) requires delivery strategies that improve drug residence within lung tissue while limiting systemic exposure. Herein, roxadustat-loaded silk fibroin nanoparticles (RXS-SKNPs) were developed and coated with gelatin (GT) to produce an MMP-2-responsive pulmonary delivery platform. RXS-SKNPs were prepared by desolvation-assisted nanoprecipitation, followed by GT coating via electrostatic interactions. The optimized GT-RXS-SKNPs showed an increase in particle size from 145.72 \u00b1 2.74 nm to 194.26 \u00b1 2.94 nm, a zeta-potential shift from \u221230.28 \u00b1 1.01\u00a0mV to \u221215.19 \u00b1 2.38 mV, and an entrapment efficiency of 72.11% \u00b1 0.81%. FTIR analysis and the increased surface-accessible amino-group signal confirmed GT coating and RXS incorporation. GT-RXS-SKNPs exhibited MMP-2-triggered colloidal remodeling and enzyme-responsive release, with cumulative RXS release increasing to 59.93% \u00b1 1.30% after 24\u00a0h under MMP-2 exposure compared with 43.70% \u00b1 1.32% in enzyme-free medium. Release followed anomalous non-Fickian behavior, indicating combined diffusion and GT shell erosion\/relaxation.\n                    <jats:italic>In vivo<\/jats:italic>\n                    , GT-RXS-SKNPs reduced plasma exposure while increasing lung AUC\n                    <jats:sub>0<\/jats:sub>\n                    \u2013\n                    <jats:sub>24<\/jats:sub>\n                    by 3.58-fold and 1.71-fold compared with free RXS and uncoated RXS-SKNPs, respectively, and prolonged lung MRT to 42.13 \u00b1 8.34\u00a0h. In bleomycin-induced PF, GT-RXS-SKNPs produced the strongest attenuation of histopathological injury, collagen deposition, myofibroblast activation, BALF inflammatory cytokines, lung hydroxyproline, TGF-\u03b21, MMP-2, MMP-9, lipid peroxidation, and antioxidant depletion. Integrated recovery analysis showed the highest overall fibrosis recovery index for GT-RXS-SKNPs (85.3%), outperforming uncoated RXS-SKNPs (60.8%) and free RXS (34.1%). Overall, GT-RXS-SKNPs improved pulmonary retention and translated enhanced lung delivery into superior antifibrotic efficacy while limiting systemic exposure.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2026.1921860","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T04:25:59Z","timestamp":1785731159000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Bioresponsive gelatin-coated silk fibroin nanoparticles enhance roxadustat therapy in experimental pulmonary fibrosis"],"prefix":"10.3389","volume":"17","author":[{"given":"Elsayed A.","family":"Elmorsy","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University","place":["Buraidah, Saudi Arabia"]},{"name":"Department of Clinical Pharmacology, Faculty of Medicine, Mansoura University","place":["Mansoura, 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