Nano-cocrystals of piperine–succinic acid and its antihyperlipidemic effect in male Wistar rats

Background: Piperine, one of the alkaloid compounds from Piper nigrum L., has been renowned for its remarkable pharmacological effects, including its antihyperlipidemic activity. However, piperine exhibits poor solubility and impairs pharmacological effectiveness. Objectives: The aim of the study was to develop piperine–succinic acid nano-cocrystals and to investigate their efficacy in reducing serum cholesterol and triglyceride levels in male Wistar rats. Methods: Nano-cocrystals were prepared by the wet milling method and characterized for solid-state properties. Antihyperlipidemic activity was tested in 24 rats, which were randomly assigned into four groups: negative control group (NaCMC 0.5%), positive control group (simvastatin 0.18 mg/kgBW), intact piperine group and nano-cocrystals piperine–succinic acid group with a dose equivalent to 40 mg/kg of the body weight. Serum total cholesterol and triglyceride levels were measured enzymatically. Results: Thermal and X-ray diffraction analyses confirmed the formation of new crystalline structures. The average particle size was 245.5 nm with a polydispersity index of 0.447 and a zeta potential value of -2.51 mV, indicating limited colloidal stability. Despite this, the nano-cocrystals significantly reduced total cholesterol and triglyceride levels compared to intact piperine (p<0.05). The duration of treatment also influenced lipid reduction (p<0.05). Conclusion: Although the formulation demonstrated enhanced bioactivity, further optimization of stability parameters is warranted to ensure long-term efficacy.