{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T03:05:27Z","timestamp":1789441527503,"version":"build-2803163510"},"reference-count":54,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2021,12,10]],"date-time":"2021-12-10T00:00:00Z","timestamp":1639094400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The study aimed to develop a new glutathione (GSH) oral formulation to enhance the delivery of GSH and counter the nephrotoxicity of the anticancer drug, cyclophosphamide (CP). A nanostructured lipid carrier glutathione formulation (GSH-NLCs) composed of glutathione (500 mg), stearic and oleic acid (300 mg, each), and Tween\u00ae 80 (2%, w\/v) was prepared through the emulsification-solvent-evaporation technique, which exhibited a 452.4 \u00b1 33.19 nm spheroidal-sized particulate material with narrow particle size distributions, \u221238.5 \u00b1 1.4 mV zeta potential, and an entrapment efficiency of 79.8 \u00b1 1.9%. The GSH formulation was orally delivered, and biologically tested to ameliorate the CP-induced renal toxicity in a rat model. Detailed renal morphology, before and after the GSH-NLCs administration, including the histopathological examinations, confirmed the ameliorating effects of the prepared glutathione formulation together with its safe oral delivery. CP-induced oxidative stress, superoxide dismutase depletion, elevation of malondialdehyde levels, depletion of Bcl-2 concentration levels, and upregulated NF-KB levels were observed and were controlled within the recommended and near normal\/control levels. Additionally, the inflammatory mediator marker, IL-1\u03b2, serum levels were marginally normalized by delivery of the GHS-NLCs formulation. Oral administration of the pure glutathione did not exhibit any ameliorating effects on the renal tissues, which suggested that the pure glutathione is reactive and is chemically transformed during the oral delivery, which affected its pharmacological action at the renal site. The protective effects of the GSH-NLCs formulation through its antioxidant and anti-inflammatory effects suggested its prominent role in containing CP-induced renal toxicity and renal tissue damage, together with the possibility of administrating higher doses of the anticancer drug, cyclophosphamide, to achieve higher and effective anticancer action in combination with the GSH-NLCs formulation.<\/jats:p>","DOI":"10.3390\/molecules26247491","type":"journal-article","created":{"date-parts":[[2021,12,13]],"date-time":"2021-12-13T01:29:33Z","timestamp":1639358973000},"page":"7491","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Nano-Structured Lipid Carrier-Based Oral Glutathione Formulation Mediates Renoprotection against Cyclophosphamide-Induced Nephrotoxicity, and Improves Oral Bioavailability of Glutathione Confirmed through RP-HPLC Micellar Liquid Chromatography"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9118-7752","authenticated-orcid":false,"given":"Adel M.","family":"Ahmad","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, South Valley University, Qena 83523, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2896-6790","authenticated-orcid":false,"given":"Hamdoon A.","family":"Mohammed","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, Qassim University, Buraydah 51452, Saudi Arabia"},{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Al-Azhar University, Cairo 11371, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5870-2676","authenticated-orcid":false,"given":"Tarek M.","family":"Faris","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics and Industrial Pharmacy, College of Pharmacy, Al-Azhar University, Cairo 11371, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abeer S.","family":"Hassan","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Faculty of Pharmacy, South Valley University, Qena 83523, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hebatallah B.","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Faculty of Pharmacy, South Valley University, Qena 83523, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmoud I.","family":"El Dosoky","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine, South Valley University, Qena 83523, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6309-847X","authenticated-orcid":false,"given":"Esam M.","family":"Aboubakr","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, South Valley University, Qena 83523, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.canep.2009.10.003","article-title":"Breast cancer as a global health concern","volume":"33","author":"Coughlin","year":"2009","journal-title":"Cancer Epidemiol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Lehmann, F., and Wennerberg, J. 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