Publication

Abstract : Polycystic ovary syndrome (PCOS) develops from hormonal imbalances, hyperandrogenism, oligomenorrhea, and the presence of multiple cystic follicles in the ovaries. The combination of oral letrozole (LTZ) for ovulation induction, accompanied by intravaginal progesterone (PG) for luteal phase support, has gained clinical success due to the ability to target multiple pathways in the pathogenesis of PCOS. However, intravaginal 8 % w/w progesterone gel available in the market (MKTD 8 % w/w PG gel) is associated with weak mucoadhesive strength, and low permeation rate, in addition to vaginal blood discharge, coitus interruptus, and local side effects such as vaginal irritation and discharge. Therefore, in the present investigation, intravaginal progesterone emulgel (PG emulgel) was developed to offer superior permeation with desirable therapeutic efficacy for the treatment of experimental PCOS. Initially, PG-nanoemulsion (PG-NE) was optimized by Quality-by-Design (QbD) employing a risk assessment matrix. The PG-NE post-optimization yielded a globule diameter of 89.74 ± 1.6 nm, with a polydispersity index (PDI) of 0.131 ± 0.08 and a zeta potential (zeta P) of −6.95 ± 0.08 mV. Next, PG-NE was amalgamated with polycarbophil (3 % w/w) using the cold dispersion method for the laboratory scale-up of PG emulgel. Intravaginal PG emulgel exhibited notable textural characteristics, and optimum viscosity along with a markedly higher ex vivo permeation rate (456.42 ± 35.14 μμg/cm2) as compared to intravaginal MKTD 8 % w/w PG gel (35.14 ± 4.90 μμg/cm2) with statistically significant difference (P < 0.0001). The in vivo study demonstrated notable modulation of lipid and oxidative stress markers, followed by recruitment and development of normal follicles. Additionally, hormone levels in PCOS were normalized when treated with oral LTZ (5 mg/kg) and intravaginal PG emulgel (1.89 ± 0.07 % w/w), compared to oral LTZ (5 mg/kg) and intravaginal MKTD 8 % w/w PG gel. Therefore, intravaginal PG emulgel offered luteal support in experimental PCOS in the reduced dose regimen and warrants further testing and validation in a clinical setting to explore translational opportunities.