{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:31:31Z","timestamp":1790699491875,"version":"4.1.0"},"reference-count":63,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007471","name":"Northern Border University","doi-asserted-by":"publisher","award":["NBU-CRP-2026-2474"],"award-info":[{"award-number":["NBU-CRP-2026-2474"]}],"id":[{"id":"10.13039\/501100007471","id-type":"DOI","asserted-by":"publisher"}]},{"award":["NBU-CRP-2026-2474"],"award-info":[{"award-number":["NBU-CRP-2026-2474"]}],"id":[{"id":"https:\/\/ror.org\/03j9tzj20","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Polymers"],"abstract":"<jats:p>Background\/Objectives: Hepatocellular carcinoma, or liver cancer, is the sixth most common cancer worldwide and the third leading cause of cancer-related mortality. Therefore, this study aimed to develop and optimise etodolac-loaded sodium deoxycholate-stabilised shellac-based polymeric nanoparticles (ETD-SDS-SHNPs) to improve the pharmacokinetic profile of etodolac (ETD) in HepG2 human hepatocellular carcinoma (HCC) cells. Methods: The nanoprecipitation method was used to prepare ETD-SDS-SHNPs, which were then optimised using a Box\u2013Behnken design and evaluated for particle size (PS), zeta potential (ZP), entrapment efficiency (EE), solid-state characterization, and in vitro drug dissolution. Furthermore, in vivo oral bioavailability, cytotoxicity, cellular uptake, and cell cycle progression were assessed. Results: The optimised ETD-SDS-SHNPs formulation showed an average PS of 192 \u00b1 1.50 nm, ZP of \u221220.2 \u00b1 0.4 mV, and EE of 81.6 \u00b1 1.42%. Differential scanning calorimetry and X-ray diffraction confirmed the reduced crystallinity of ETD-SDS-SHNPs, indicating partial amorphisation of the drug in the formulation. Field-emission scanning electron microscopy revealed predominantly spherical nanoparticles with relatively smooth surfaces. The peak plasma concentration (Cmax) of ETD-SDS-SHNPs (11.86 \u00b1 0.12 \u00b5g\/mL) was significantly higher than that of the pure ETD (7.15 \u00b1 0.14 \u00b5g\/mL). Similarly, the AUC0\u2013t for ETD-SDS-SHNPs (351.63 \u00b1 4.59 \u00b5g\u00b7h\/mL) was approximately 1.48-fold greater than that of the pure drug (236.09 \u00b1 4.60 \u00b5g\u00b7h\/mL), indicating enhanced bioavailability. ETD-SDS-SHNPs demonstrated dose-dependent enhancement of cytotoxicity against HepG2 cells, accompanied by S-phase cell cycle arrest and increased cellular uptake. Conclusions: ETD-SDS-SHNPs formulation offers an enhanced passive, efficient, and safer nanocarrier platform for repurposing etodolac in liver cancer therapy, showing significant promise for improving clinical outcomes in HCC treatment.<\/jats:p>","DOI":"10.3390\/polym18151863","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T17:01:46Z","timestamp":1785344506000},"page":"1863","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Development and Optimization of Sodium Deoxycholate-Stabilised Shellac-Based Polymeric Nanoparticles for Enhanced Pharmacokinetics and Anticancer Activity of Etodolac in Hepatocellular Carcinoma"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1898-2957","authenticated-orcid":false,"given":"Ritesh A.","family":"Fule","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Science, Dadasaheb Balpande College of Pharmacy, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur 440037, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aishwarya S.","family":"Rangurwar","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Science, Dadasaheb Balpande College of Pharmacy, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur 440037, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0472-2679","authenticated-orcid":false,"given":"Pankaj D.","family":"Nagpure","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Science, Dadasaheb Balpande College of Pharmacy, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur 440037, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3843-1137","authenticated-orcid":false,"given":"Helal G.","family":"Alanazi","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2811-4387","authenticated-orcid":false,"given":"Mohammed M.","family":"Alruwaili","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Technology, College of Applied Medical Sciences, Northern Border University, Arar 73213, Saudi Arabia"},{"name":"Center for Health Research, Northern Border University, Arar 73213, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6372-890X","authenticated-orcid":false,"given":"Md Ali","family":"Mujtaba","sequence":"additional","affiliation":[{"name":"Center for Health Research, Northern Border University, Arar 73213, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gamal Osman","family":"Elhassan","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, Qassim University, Buraidah 51452, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siham","family":"Abdoun","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, Qassim University, Buraidah 51452, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1038\/nrclinonc.2015.169","article-title":"Drug repurposing in oncology\u2014Patient and health systems opportunities","volume":"12","author":"Bertolini","year":"2015","journal-title":"Nat. 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