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Targeted delivery of empagliflozin via glycyrrhetinic-acid-modified lipid nanoparticles for metabolic dysfunction–associated steatotic liver disease therapy
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DOI：10.1016/j.matdes.2025.115391.png)
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Abstract
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• Glycyrrhetinic-acid-modified lipid nanoparticles achieved 89 % encapsulation efficiency and roughly tripled the cellular uptake of empagliflozin by human hepatocytes in vitro. • The targeted formulation lowered intracellular lipid droplets and normalised the expression of sterol regulatory element binding protein-1c, fatty acid synthase, and sirtuin-1 in free-fatty-acid-challenged LO2 liver cells. • In a high-fat diet–induced hepatic steatosis mouse model relevant to metabolic dysfunction–associated steatotic liver disease (MASLD), the formulation restored serum triglyceride, total cholesterol, low-density- and high-density-lipoprotein cholesterol toward normal values and markedly relieved hepatic steatosis. • Treatment reduced circulating interleukin-6, interleukin-1β, and tumour necrosis factor-α, improved oral glucose tolerance and insulin tolerance test outcomes, and lowered the homeostatic model assessment of insulin-resistance index. • The delivery system provided sustained drug release, caused less than 5 % haemolysis, and produced no histological or biochemical toxicity in major organs, demonstrating excellent biosafety.
Keywords:
Metabolic Dysfunction–Associated Steatotic Liver Disease
Empagliflozin
Lipid nanoparticles
Glycyrrhetinic acid targeting
Metabolic dysfunction
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