Gallic acid-loaded chitosomes: A promising strategy to improve metabolic and endocrine function in PCOS

Abstract

Polycystic ovarian syndrome (PCOS) is a prevalent endocrine–metabolic disorder characterized by insulin resistance, dyslipidemia, chronic inflammation, and impaired reproductive function. Gallic acid (GA), a naturally occurring polyphenol, exhibits potent anti-inflammatory and antioxidant effects; however, its therapeutic potential is limited by poor aqueous solubility and low bioavailability. This study reports the development of a novel GA delivery system based on chitosan-coated liposomes (chitosomes). The formulation was systematically optimized using an I-optimal experimental design, investigating the effects of chitosan concentration (X1), drug amount (X2), and chitosan molecular weight (X3) on entrapment efficiency % (Y1), particle size (Y2), and zeta potential (Y3). Furthermore, the optimized system was mechanistically evaluated in a PCOS rat model, representing a strategy for GA delivery that has not been previously reported.GA-loaded liposomes were prepared via thin-film hydration and subsequently coated with chitosan. The optimized formulation demonstrated high entrapment efficiency (68 ± 1.76%), nanoscale particle size (223.70 ± 1.34 nm), and a strong positive surface charge (+42.20 ± 2.11 mV). In-vitro studies showed sustained GA release compared to free GA. In vivo studies demonstrated that the optimized chitosomes significantly ameliorated metabolic and hormonal disturbances, including improved insulin sensitivity, normalization of the LH/FSH ratio, and reduction in serum cholesterol. These effects were further supported by decreased oxidative stress and suppression of the pro-inflammatory NLRP3/IL-1β signaling pathway. In conclusion, the optimized chitosomes represent a promising nanocarrier platform that enhances GA bioavailability and provides an effective strategy for managing the metabolic and inflammatory complications associated with PCOS.