GC-MS-GUIDED DEVELOPMENT AND PRECLINICAL EVALUATION OF A GLYCINE MAX-DERIVED PHYTOCOMPOUND-LOADED ZIRCONIA NANOCONSTRUCT IN LETROZOLE-INDUCED POLYCYSTIC OVARY SYNDROME

Abstract

Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine-metabolic disorder for which phytochemical and nanocarrier-based strategies are being explored as adjuncts to conventional therapy. This study integrated gas chromatography-mass spectrometry (GC-MS) profiling of polarity-based Glycine max (L.) Merr. seed extracts, physicochemical characterization of a carbonic acid, 2-dimethylaminoethyl isobutyl ester-loaded zirconia nanoconstruct (CADIE-ZrO₂), and comparative preclinical testing in letrozole-induced PCOS. GC-MS generated 325 library-matched phytochemical assignments, of which 30 compounds were retained in the finalized research dataset. CADIE-ZrO₂ showed an absorption maximum near 388 nm, FTIR bands compatible with an organic surface-associated layer and the zirconia core, preserved crystalline reflections at approximately 24.8°, 30.2°, 35.1°, 40.3°, 45.2°, 50.4° and 60.2° 2θ, irregular-to-sub-hexagonal morphology with mild agglomeration, a dominant hydrodynamic population near 86 nm, and a mean zeta potential of approximately 31.4 mV. Adult female Wistar rats were allocated to vehicle, letrozole-PCOS, positive-control, four seed extract, free-CADIE, ZrO₂ and CADIE-ZrO₂ groups. The PCOS group showed persistent diestrus, increased LH and testosterone, and reduced FSH, progesterone and estradiol. CADIE-ZrO₂ reduced LH (1.2 ± 0.4 vs 5.87 ± 0.31 mIU/mL) and testosterone (1.2 ± 0.4 vs 6.15 ± 1.2 ng/dL), while increasing FSH (6.03 ± 0.32 vs 0.03 ± 0.01 mIU/mL) and progesterone (9.72 ± 2.3 vs 4.1 ± 0.6 pg/dL). Ovarian histology showed a marked reduction in cystic pathology with restoration of corpus luteum-containing architecture in the loaded-nanoconstruct group, while uterine, pancreatic, renal and hepatic microarchitecture was largely preserved. Hepatorenal biochemical responses were mixed: urea and creatinine moved toward vehicle values, whereas AST remained elevated. Collectively, the findings support CADIE-ZrO₂ as an exploratory preclinical formulation with selective endocrine and histological benefit, release, pharmacokinetic, biodistribution and longer-term safety studies before translation.