Curcumin-Loaded Long-Circulation Liposomes Ameliorate Insulin Resistance in Type 2 Diabetic Mice

Int J Nanomedicine. 2024 Nov 19:19:12099-12110. doi: 10.2147/IJN.S487519. eCollection 2024.

Abstract

Introduction: Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterised by insulin resistance, hyperglycaemia, and inflammation, with oxidative stress contributing to its progression. Curcumin (CUR), known for its anti-inflammatory, antioxidant, and insulin sensitising effects, has shown potential for the treatment of T2DM but is limited by low solubility and bioavailability. This study investigated long-circulating curcumin-loaded liposomes (CUR-LPs) to improve curcumin stability, solubility, and circulation and assessed their effect on insulin resistance in a murine model of T2DM.

Methods: CUR-LPs were prepared using the ethanol injection method and characterized for morphology, particle size, zeta potential, encapsulation efficiency, drug-loading capacity, and in vitro release. Cell viability was tested on murine L929 cells. In a T2DM murine model, after four weeks of CUR-LP treatment, inflammatory markers TNF-α and IL-6 were measured by real-time polymerase chain reaction, and liver tissues were analyzed for glutathione (GSH) and superoxide dismutase (SOD) via colorimetry.

Results: CUR-LPs were spherical, with an average diameter of (249 ± 2.3) nm and a zeta potential of (-33.5 ± 0.8) mV. They exhibited an encapsulation efficiency of (99.2 ± 0.5) %and a drug-loading capacity of (1.63 ± 0.02) %. CUR embedding in liposomes significantly maintained CUR release. In L929 cells, over 80% viability was maintained at 12 uM CUR concentration after 24 h. In HFD/STZ-induced T2DM mice, CUR-LPs improved blood glucose and insulin levels more efficiently than free CUR, and CUR-LPs also reduced hepatic inflammation (TNF-α, IL-6), enhanced hepatic GSH and SOD, and attenuated liver injury.

Conclusion: CUR-LPs improved glucose metabolism and insulin resistance in HFD/STZ-induced T2DM mice, which may be associated with a decrease in liver inflammation and oxidative stress.

Keywords: T2DM; curcumin; glucose metabolism; insulin resistance; liposomes; oxidative stress.

MeSH terms

  • Animals
  • Blood Glucose / analysis
  • Blood Glucose / drug effects
  • Cell Line
  • Cell Survival / drug effects
  • Curcumin* / administration & dosage
  • Curcumin* / chemistry
  • Curcumin* / pharmacokinetics
  • Curcumin* / pharmacology
  • Diabetes Mellitus, Experimental / drug therapy
  • Diabetes Mellitus, Type 2* / drug therapy
  • Glutathione / metabolism
  • Insulin Resistance*
  • Interleukin-6 / blood
  • Interleukin-6 / metabolism
  • Liposomes* / administration & dosage
  • Liposomes* / chemistry
  • Liposomes* / pharmacology
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Oxidative Stress / drug effects
  • Particle Size
  • Superoxide Dismutase / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Curcumin
  • Liposomes
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Blood Glucose
  • Glutathione
  • Superoxide Dismutase

Grants and funding

This project was supported by the grants given to Shu-Lan Qin from Guangdong Provincial Administration of Traditional Chinese Medicine Bureau, China (20222141), Guangdong Pharmaceutical Association of Clinical Drug Research Fund, China (2022JZ19). Kang-Xin Li (Project grant202201011087) funded this project at a later stage.