Targeted Therapeutic Strategies for Polycystic Ovary Syndrome Using Polyphenolic Bioactive Compound-Loaded Polymeric Nanoparticles: A Systematic Review

Polycystic Ovary Syndrome (PCOS) is a complex endocrine–metabolic disorder affecting women of reproductive age, characterized by hyperandrogenism, ovulatory dysfunction, polycystic ovarian morphology, insulin resistance, oxidative stress, and chronic low-grade inflammation. Current pharmacological interventions predominantly provide symptomatic relief and are often limited by suboptimal efficacy, systemic side effects, and poor long-term adherence. In recent years, polyphenolic bioactive compounds have gained significant attention as potential multitarget therapeutic agents for PCOS due to their antioxidant, anti-inflammatory, insulin-sensitizing, and steroidogenesis-modulating properties. However, their clinical translation is constrained by poor solubility, low bioavailability, rapid metabolism, and limited ovarian targeting. This systematic review critically evaluates the emerging role of polyphenolic compound–loaded polymeric nanoparticles as advanced drug delivery systems for targeted PCOS therapy. A comprehensive literature search was conducted across major scientific databases to identify in-vitro, in-vivo, and translational studies investigating polymeric nanoparticle formulations encapsulating polyphenols for reproductive and endocrine applications. The review highlights nanoparticle design strategies, polymer selection, physicochemical characteristics, functional attributes, and mechanisms underlying improved therapeutic efficacy. Evidence from preclinical studies demonstrates that nanoencapsulation enhances polyphenol stability, bioavailability, and ovarian accumulation, leading to significant improvements in insulin resistance, oxidative stress, inflammation, hormonal imbalance, and follicular development in PCOS models. Furthermore, the review addresses safety, biocompatibility, and toxicological considerations of polymeric nanocarriers, emphasizing their favorable reproductive safety profiles when fabricated from biodegradable and biocompatible polymers. Regulatory challenges, clinical translation barriers, and future perspectives in PCOS nanomedicine are also discussed. Overall, polyphenolic compound–loaded polymeric nanoparticles represent a promising, mechanism-driven, and targeted therapeutic approach for PCOS management, with the potential to shift treatment paradigms toward precision nanomedicine pending robust clinical validation.