Polymeric nanoparticles containing 4-methoxychalcone attenuates hyperglycemia in diabetes-induced mice

Objective(s): Diabetes mellitus is a chronic metabolic disorder characterized by persistent disturbances in glucose homeostasis. Novel therapeutic strategies are needed to improve glycemic control while minimizing toxicity. This study investigated the hypoglycemic potential of 4‑methoxychalcone (MPP), synthesized via the Claisen–Schmidt reaction, and evaluated the efficacy of its nanoencapsulation in diabetic mice.Methods: MPP was synthesized and subsequently nanoencapsulated (NCs) using ethanol, isopropyl palmitate, and organic phase surfactants. Nanocarriers were characterized by particle size, polydispersity index (PDI), zeta potential, and morphology through transmission electron microscopy (TEM). Diabetes was induced in CL57/6BL mice using streptozotocin/nicotinamide. Animals were treated for 28 days with free MPP (200 mg/kg), metformin (200 mg/kg), or NCs (10 mg/kg). Biochemical assays were performed on blood samples, and histological analyses were conducted on liver tissues.Results: NCs exhibited a mean particle size of 187 nm, zeta potential of −19.9 mV, and PDI of 0.21, demonstrating stability across varying temperatures and pH conditions. TEM confirmed spherical morphology and uniform distribution. Both metformin (176.33 ± 44.68 mg/dL, p < 0.0001) and NCs (163.2 ± 76.3 mg/dL, p < 0.0001) significantly reduced blood glucose levels. NCs further normalized glycated hemoglobin (HbA1c) without evidence of hepatotoxicity, as indicated by low malondialdehyde levels and preserved liver histology.Conclusion: Nanoencapsulation of MPP enhances its antidiabetic efficacy, enabling therapeutic effects at lower doses while reducing toxicity risks. This strategy represents a promising approach for the development of safer and more effective antidiabetic interventions.