{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T00:29:48Z","timestamp":1788654588501,"version":"build-2803163510"},"reference-count":83,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,11,26]],"date-time":"2021-11-26T00:00:00Z","timestamp":1637884800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007614","name":"Al Jouf University","doi-asserted-by":"publisher","award":["DSR2020-04-428"],"award-info":[{"award-number":["DSR2020-04-428"]}],"id":[{"id":"10.13039\/501100007614","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Pulmonary fibrosis is a serious ailment that may progress to lung remodeling and demolition, where the key participants in its incidence are fibroblasts responding to growth factors and cellular calcium swinging. Calcium channel blockers, like nifedipine (NFD), may represent auspicious agents in pulmonary fibrosis treatment. Unfortunately, NFD bears complicated pharmacodynamics and a diminished systemic bioavailability. Thus, the current study aimed to develop a novel, non-invasive nanoplatform for NFD for direct\/effective pulmonary targeting via intratracheal instillation. A modified solvent emulsification\u2013evaporation method was adopted for the fabrication of NFD-nanocomposites, integrating poly(D,L-lactide-co-glycolide) (PLGA), chitosan (CTS), and polyvinyl alcohol, and optimized for different physiochemical properties according to the 32 full factorial design. Additionally, the aerodynamic behavior of the nanocomposites was scrutinized through cascade impaction. Moreover, the pharmacokinetic investigations were conducted in rats. Furthermore, the optimum formulation was tested in bleomycin-induced pulmonary fibrosis in rats, wherein fibrotic and oxidative stress parameters were measured. The optimum nanocomposites disclosed a nanosized spherical morphology (226.46 nm), a high entrapment efficiency (61.81%) and a sustained release profile over 24 h (50.4%). As well, it displayed a boosted in vitro lung deposition performance with a mass median aerodynamic diameter of 1.12 \u00b5m. Pharmacokinetic studies manifested snowballed bioavailability of the optimal nanocomposites by 3.68- and 2.36-fold compared to both the oral and intratracheal suspensions, respectively. The intratracheal nanocomposites revealed a significant reduction in lung fibrotic and oxidative stress markers notably analogous to normal control besides repairing abnormality in TGF-\u03b2\/\u03b2-catenin pathway. Our results conferred a compelling proof-of-principle that NFD-CTS-PLGA nanocomposites can function as a promising nanoparadigm for pulmonary fibrosis management.<\/jats:p>","DOI":"10.3390\/ph14121225","type":"journal-article","created":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T23:22:56Z","timestamp":1638314576000},"page":"1225","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Intratracheally Inhalable Nifedipine-Loaded Chitosan-PLGA Nanocomposites as a Promising Nanoplatform for Lung Targeting: Snowballed Protection via Regulation of TGF-\u03b2\/\u03b2-Catenin Pathway in Bleomycin-Induced Pulmonary Fibrosis"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4083-6024","authenticated-orcid":false,"given":"Mohammed H.","family":"Elkomy","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, Jouf University, Sakaka 72388, Saudi Arabia"},{"name":"Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rasha A.","family":"Khallaf","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6737-8142","authenticated-orcid":false,"given":"Mohamed O.","family":"Mahmoud","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0503-685X","authenticated-orcid":false,"given":"Raghda R. S.","family":"Hussein","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt"},{"name":"Department of Clinical Pharmacy, Faculty of Pharmacy, Modern University for Technology and Information, Cairo 12055, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5686-9416","authenticated-orcid":false,"given":"Asmaa M.","family":"El-Kalaawy","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Beni-Suef University, Beni-Suef 62511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7982-5827","authenticated-orcid":false,"given":"Abdel-Razik H.","family":"Abdel-Razik","sequence":"additional","affiliation":[{"name":"Department of Histology, Faculty of Veterinary Medicine, Beni-Suef University, Beni-Suef 62511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6226-5192","authenticated-orcid":false,"given":"Heba M.","family":"Aboud","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"221","DOI":"10.5858\/arpa.2015-0288-SA","article-title":"Update on pulmonary fibrosis: Not all fibrosis is created equally","volume":"140","author":"Smith","year":"2016","journal-title":"Arch. 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