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Pharmaceuticals
Volume 19
Issue 6
10.3390/ph19060898
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Article

Engineering Selenium–Chitosan Nanoparticles for Enhanced Hepatic Delivery of Sunitinib and Improved In Vitro Anticancer Activity in Hepatocellular Carcinoma Models

by
Ahmed S.G. Srag El-Din
1,*,
Eman Hamza
2,*,
Ahmed Y. Kira
1,
Sameh Saber
3,
Mona H. Zohny
4,
Ohoud Y. Alshehri
2,
Reham A. Al-Dhelaan
2,
Eslam Osama Mohamed
5 and
Heba I. Elagamy
1
1
Department of Pharmaceutics, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa 11152, Egypt
2
Department of Biochemistry, College of Medicine, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 13317, Saudi Arabia
3
Department of Pharmacology, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa 11152, Egypt
4
Department of Biochemistry, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa 11152, Egypt
5
Department of Biotechnology, Chemistry, and Pharmacy, University of Siena, 53100 Siena, Italy
*
Authors to whom correspondence should be addressed.
Pharmaceuticals 2026, 19(6), 898; https://doi.org/10.3390/ph19060898 (registering DOI)
Submission received: 5 May 2026 / Revised: 28 May 2026 / Accepted: 2 June 2026 / Published: 5 June 2026
(This article belongs to the Topic Advanced Nanotechnology in Drug Delivery Systems)
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Abstract

Background/Objectives: Hepatocellular carcinoma (HCC) remains difficult to treat because systemic therapy is constrained by limited selectivity, resistance, and toxicity. This study aimed to engineer selenium–chitosan nanoparticles loaded with sunitinib (SeNPs-Ch-SUN) to enhance hepatic delivery and improve anticancer activity against HCC. Methods: The developed system was characterized for particle size (PS), zeta potential (ZP), loading efficiency (LE%), in vitro release, and storage stability. Their cytotoxicity was evaluated in parental HepG2 and Huh-7 cells, multidrug-resistant HepG2 cells, SUN-resistant Huh-7 cells, and THLE-2 normal hepatocytes. In vivo hepatic distribution after intravenous administration was also assessed in rats. Results: SeNPs-Ch-SUN exhibited a mean PS of 93.62 ± 1.06 nm, positive ZP of +24.47 ± 1.31 mV, and LE of 83.8 ± 2.16%. FTIR supported drug association with the chitosan-stabilized selenium system. Compared with free sunitinib, SeNPs-Ch-SUN exhibited sustained drug release, with 51.17 ± 1.26% released at 24 h, whereas the free drug was almost completely released within 3 h. This controlled-release behavior translated in vivo into prolonged hepatic retention and superior liver exposure after intravenous administration. SeNPs-Ch-SUN significantly increased liver AUC0-24 to 77.23 ± 10.56 µg/g·h, compared with 36.39 ± 9.66 µg/g·h for free SUN, corresponding to an approximately 2.1-fold increase in hepatic exposure. SeNPs-Ch-SUN enhanced cytotoxicity in parental and resistant HCC models, lowered IC50 values, improved selectivity toward malignant cells, and reduced resistance index (RI) in MDR-HepG2 cells, while maintaining reduced toxicity toward normal hepatocytes relative to the free SUN. Conclusions: SeNPs-Ch-SUN represents a promising liver-directed nanoplatform for sunitinib delivery.
Keywords: sunitinib; selenium–chitosan nanoparticles; MDR-HepG2 cells; cytotoxicity; hepatic distribution; hepatocellular carcinoma sunitinib; selenium–chitosan nanoparticles; MDR-HepG2 cells; cytotoxicity; hepatic distribution; hepatocellular carcinoma
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MDPI and ACS Style

Srag El-Din, A.S.G.; Hamza, E.; Kira, A.Y.; Saber, S.; Zohny, M.H.; Alshehri, O.Y.; Al-Dhelaan, R.A.; Mohamed, E.O.; Elagamy, H.I. Engineering Selenium–Chitosan Nanoparticles for Enhanced Hepatic Delivery of Sunitinib and Improved In Vitro Anticancer Activity in Hepatocellular Carcinoma Models. Pharmaceuticals 2026, 19, 898. https://doi.org/10.3390/ph19060898

AMA Style

Srag El-Din ASG, Hamza E, Kira AY, Saber S, Zohny MH, Alshehri OY, Al-Dhelaan RA, Mohamed EO, Elagamy HI. Engineering Selenium–Chitosan Nanoparticles for Enhanced Hepatic Delivery of Sunitinib and Improved In Vitro Anticancer Activity in Hepatocellular Carcinoma Models. Pharmaceuticals. 2026; 19(6):898. https://doi.org/10.3390/ph19060898

Chicago/Turabian Style

Srag El-Din, Ahmed S.G., Eman Hamza, Ahmed Y. Kira, Sameh Saber, Mona H. Zohny, Ohoud Y. Alshehri, Reham A. Al-Dhelaan, Eslam Osama Mohamed, and Heba I. Elagamy. 2026. "Engineering Selenium–Chitosan Nanoparticles for Enhanced Hepatic Delivery of Sunitinib and Improved In Vitro Anticancer Activity in Hepatocellular Carcinoma Models" Pharmaceuticals 19, no. 6: 898. https://doi.org/10.3390/ph19060898

APA Style

Srag El-Din, A. S. G., Hamza, E., Kira, A. Y., Saber, S., Zohny, M. H., Alshehri, O. Y., Al-Dhelaan, R. A., Mohamed, E. O., & Elagamy, H. I. (2026). Engineering Selenium–Chitosan Nanoparticles for Enhanced Hepatic Delivery of Sunitinib and Improved In Vitro Anticancer Activity in Hepatocellular Carcinoma Models. Pharmaceuticals, 19(6), 898. https://doi.org/10.3390/ph19060898

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