Naringenin-loaded niosomal vaginal in situ gel: preclinical study in polycystic ovary syndrome-induced female Wistar rats

Aim This study aims to develop and assess Naringenin-loaded niosomal vaginal in situ 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 Naringenin-loaded niosomes were formulated by ethanol injection method and a 33Box-Behnken design (DESIGN EXPERT® Software) with five center points was generated, yielding 17 experimental runs. They were characterized for globule size, percent entrapment efficiency, zeta potential, and polydispersity index. The optimized batch was incorporated into the in situ gel. Vaginal irritancy and in vivo studies were conducted in female Wistar rats to evaluate the therapeutic efficacy of the prepared formulation in the treatment of Polycystic Ovary Syndrome.Results An 18% concentration of Pluronic F-127 was identified as optimal for gel formulation, and various evaluations, including in vitro drug release, diffusion studies, in vivo vaginal irritancy, histopathological analysis and short-term stability studies, were performed. The optimized niosomal formulation exhibited a vesicle size of 158.1 nm, an entrapment efficiency of 71.68%, a zeta potential of −28.6 mV and a drug content of 70.79 ± 1.95%. Transmission Electron Microscopy confirmed the nanoscale globule size, while the in vitro drug release rate for the niosomal formulation was 74.104%. The gel showed a viscosity range from 192.71 ± 1.23 cps to 1756.43 ± 7.46 cps as the temperature increased from 25 ± 2.0 °C to 38 ± 2.0 °C. In vitro diffusion studies showed 84.67% drug release. In vivo 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 The Naringenin-loaded niosomal vaginal in situ gel offers significant potential in managing PCOS with enhanced drug delivery and safety profiles.