An insight to development and in-vitro, ex-vivo, in-vivo study of naringenin nanoparticles against letrozole induced polycystic ovarian syndrome in female wistar rats

Abstract

The biocompatible and biodegradable polymer polylactic-co-glycolic acid (PLGA) 50:50 was used to fabricate Naringenin Nanoparticles. Development of Nanoparticles were optimized by using 32 factorial designs to study the impact of the PLGA concentration and High-pressure homogenizer cycles on the particle size, Polydispersity index (PDI), and % entrapment efficiency (%EE). The optimized batch was examined for several characteristics, including DSC, SEM, in vitro drug release study, etc. Prepared nano-formulation was subjected to assess the animals PCOS induced by the letrozole. To assess the animals for PCOS, letrozole was first given to them. Five groups were created at random: Normal control, Let group (PCOS induced), Naringenin Nanoparticles 50 mg/kg (NAR1), Naringenin Nanoparticles 100 mg/kg (NAR2), Clomiphene citrate 1 mg/kg (Clomi citrate). The expression of SIRT1 and PGC-1α in the ovary was examined using the ELISA technique, as well as alterations to the estrus cycle, body weight, ovarian activity, serum levels of hormones such as testosterone (TTST), estradiol (E), luteinizing hormone (LH), follicle-stimulating hormone (FSH), glucose metabolism, and ovarian function. Additionally, the fecal microbiome's gut makeup was examined. To conclude, naringenin-loaded PLGA nanoparticles (NAR1 and NAR2) showed a protective impact on the concentrations of several sex hormones, the composition of the gut microbiota, as well as on MDA, SOD, and CAT, and GSH levels and avoided the ovarian morphological modification in the letrozole-induced PCOS. The use of NAR1 and NAR2 dispersion is a promising option for PCOS treatment, according to the current study's findings.