Recent Advances in Nanodelivery Systems for Polyphenols in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): An update
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) represents the most prevalent chronic liver disorder worldwide, closely linked to obesity, insulin resistance, and type 2 diabetes mellitus. Despite its rising global burden, there are currently no approved pharmacological therapies targeting MASLD pathogenesis directly. Polyphenolic compounds have demonstrated promising hepatoprotective, antioxidant, and anti-inflammatory properties in preclinical models; however, their poor stability, limited solubility, and low bioavailability hinder clinical translation. This review summarizes the latest advances in nano-drug delivery systems (NDDSs) designed to enhance the therapeutic potential of polyphenols in MASLD. Various nanocarrier platforms, including inorganic, lipid-based, polymeric, and hybrid nanosystems, are discussed with emphasis on their mechanisms of action, pharmacokinetic advantages, hepatocyte-targeting strategies, and translational challenges. Emerging NDDSs markedly enhance polyphenol pharmacodynamics through enhanced intestinal absorption, controlled release, and targeted hepatic accumulation. Lipid-based carriers (liposomes, solid lipid nanoparticles, nanoemulsions, and nanostructured lipid carriers) demonstrate excellent oral bioavailability and safety, whereas polymeric and inorganic systems offer multifunctional therapeutic synergy by modulating oxidative stress, lipid metabolism, and inflammatory pathways. Recent clinical evidence, including nano-micellar curcumin formulations, suggests translational feasibility and safety in MASLD patients. Nevertheless, long-term biosafety, scalability, and interindividual variability remain key challenges for clinical application. Therefore, polyphenols loaded with nanocarrier systems offer a multifaceted therapeutic approach to address the complex metabolic, inflammatory, and fibrotic processes underlying MASLD. Future research should prioritize clinical validation, mechanistic standardization, and regulatory alignment to enable the transition from preclinical innovation to precision nanomedicine in metabolic liver diseases.
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9. Ajmera V, Cepin S, Tesfai K, Hofflich H, Cadman K, Lopez S, et al. A prospective study on the prevalence of NAFLD, advanced fibrosis, cirrhosis and hepatocellular carcinoma in people with type 2 diabetes. J Hepatol. 2023;78(3):471-8. https://doi.org/10.1016/j.jhep.2022.11.010.
10. Maher JJ, Leon P, Ryan JC. Beyond insulin resistance: Innate immunity in nonalcoholic steatohepatitis. Hepatology. 2008;48(2):670-8. https://doi.org/10.1002/hep.22399.
11. Sattari M, Ostadmohammadi K, Hajian H, Karimpour A, Sedghgou F, Sattari M, Panahi G. Fisetin as a Promising Agent in Non-Alcoholic Fatty Liver Disease: Insights into Pathogenic Mechanisms and Therapeutic Potential. Acta Biochim Iran. 2025. https://doi.org/10.18502/abi.v2i4.19106
12. Czaja MJ. JNK regulation of hepatic manifestations of the metabolic syndrome. Trends Endocrinol Metab. 2010;21(12):707-13. https://doi.org/10.1016/j.tem.2010.08.010.
13. Bednarz K, Kowalczyk K, Cwynar M, Czapla D, Czarkowski W, Kmita D, et al. The Role of Glp-1 Receptor Agonists in Insulin Resistance with Concomitant Obesity Treatment in Polycystic Ovary Syndrome. Int J Mol Sci. 2022;23(8). https://doi.org/10.3390/ijms23084334.
14. Welch RD, Billon C, Losby M, Bedia-Diaz G, Fang Y, Avdagic A, et al. Emerging Role of Nuclear Receptors for the Treatment of NAFLD and NASH. Metabolites. 2022;12(3). https://doi.org/10.3390/metabo12030238.
15. Ma K, Saha PK, Chan L, Moore DD. Farnesoid X receptor is essential for normal glucose homeostasis. J Clin Invest. 2006;116(4):1102-9. https://doi.org/10.1172/jci25604.
16. Staels B, Butruille L, Francque S. Treating NASH by targeting peroxisome proliferator-activated receptors. J Hepatol. 2023;79(5):1302-16. https://doi.org/10.1016/j.jhep.2023.07.004.
17. Wu CW, Chu ES, Lam CN, Cheng AS, Lee CW, Wong VW, et al. PPARgamma is essential for protection against nonalcoholic steatohepatitis. Gene Ther. 2010;17(6):790-8. https://doi.org/10.1038/gt.2010.41.
18. Dufour JF, Anstee QM, Bugianesi E, Harrison S, Loomba R, Paradis V, et al. Current therapies and new developments in NASH. Gut. 2022;71(10):2123-34. https://doi.org/10.1136/gutjnl-2021-326874.
19. Sberna AL, Bouillet B, Rouland A, Brindisi MC, Nguyen A, Mouillot T, et al. European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD) and European Association for the Study of Obesity (EASO) clinical practice recommendations for the management of non-alcoholic fatty liver disease: evaluation of their application in people with Type 2 diabetes. Diabet Med. 2018;35(3):368-75. https://doi.org/10.1111/dme.13565.
20. Sanyal AJ, Chalasani N, Kowdley KV, McCullough A, Diehl AM, Bass NM, et al. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med. 2010;362(18):1675-85. https://doi.org/10.1056/nejmc1006581.
21. Zeng J, Fan JG, Francque SM. Therapeutic management of metabolic dysfunction associated steatotic liver disease. United European Gastroenterol J. 2024;12(2):177-86. https://doi.org/10.1002/ueg2.12525.
22. Rinella ME, Neuschwander-Tetri BA, Siddiqui MS, Abdelmalek MF, Caldwell S, Barb D, et al. AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease. Hepatology. 2023;77(5):1797-835. https://doi.org/10.1097/hep.0000000000000323.
23. Keam SJ. Resmetirom: First Approval. Drugs. 2024;84(6):729-35. https://doi.org/10.1007/s40265-024-02045-0.
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| Files | ||
| Issue | Vol 3 No 3 (2025) | |
| Section | Review Article(s) | |
| Keywords | ||
| MASLD NAFLD polyphenols nano-drug delivery systems (NDDSs) Phytochemicals | ||
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How to Cite
1.
Ghaffari T, Bahramzadeh A, Meshkani R. Recent Advances in Nanodelivery Systems for Polyphenols in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): An update. ABI. 2025;3(3):133-149.
