Chitosan/γ-polyglutamic acid-based Pickering emulsion gel: A promising transdermal carrier for crocetin

Crocetin (CT), a natural carotenoid dicarboxylic acid known for its high medicinal value, faces challenges such as poor water solubility, low bioavailability and instability, limiting its therapeutic applications. To overcome these challenges, this study introduces a novel Pickering emulsion gel stabilized by naturally sourced chitosan (CS) and γ -polyglutamic acid ( γ -PGA) nanoparticles (CS/ γ -PGA NPs) as a potential transdermal carrier for CT. The CS/ γ -PGA NPs were synthesized using an electrostatic crosslinking method pretreated by mechanical ball-milling, producing uniform and stable nanoparticles. These NPs stabilized a CT-loaded Pickering emulsion gel (CT-PE) with cornmint oil as the oil phase, achieving up to 98.53 % encapsulation efficiency. The CT-PE exhibited enhanced rheological properties, storage stability, sustained and targeted in vitro transdermal release, potent antioxidant activity, and effective antimicrobial effects with no cytotoxicity. Microstructural analysis revealed a dense network of aggregated particles forming a moderately strong gel structure, wherein encapsulated CT enhances emulsion stability through interaction with the gel network. The synergy between CS and γ -PGA facilitated a biocompatible and efficient carrier system, markedly boosting CT's therapeutic effectiveness. These results highlight CT-PE's potential as an effective transdermal carrier for CT, promising for future dermatological treatments and drug delivery systems.