Naringenin-Loaded Niosomal Vaginal <i>In Situ</i> Gel: Preclinical Study in Polycystic Ovary Syndrome-Induced Female Wistar Rats

AIM: gel for the effective management of Polycystic Ovary Syndrome. The objectives include enhancing drug permeation, ensuring sustained release and mitigating the oral side effects associated with naringenin. METHOD: studies were conducted in female Wistar rats to evaluate the therapeutic efficacy of the prepared formulation in the treatment of Polycystic Ovary Syndrome. RESULTS: administration of the Naringenin loaded niosomal vaginal gel markedly lowered body weight and fasting blood glucose (p < 0.001) and reestablished hormonal, lipid, and antioxidant homeostasis by decreasing serum testosterone, triglycerides, total cholesterol, and low-density lipoprotein, while elevating progesterone, high-density lipoprotein, superoxide dismutase, catalase, and glutathione levels along with a concurrent decline in malondialdehyde (p < 0.001). Histopathological findings demonstrated fewer cystic follicles, restored folliculogenesis, and normalized adipocyte structure, and vaginal irritancy assessments verified the formulation's safety and therapeutic effectiveness against mifepristone-induced Polycystic Ovary Syndrome. Short-term stability studies demonstrated the optimized formulation's stability at 4 °C. CONCLUSION: gel offers significant potential in managing PCOS with enhanced drug delivery and safety profiles.