Abstract

Baicalin (BA) is a potent flavonoid with antioxidant and anti-inflammatory properties; however, its clinical application is limited due to poor solubility and permeability. The present study aimed to develop an innovative baicalin-loaded essential oil-based lipid nanoparticle hydrogel (BA-NP-G) utilising rosemary oil (RO) as both an excipient and a therapeutic synergist for potential use in skin inflammatory disorders. BA-loaded lipid nanoparticles (BA-NPs) were formulated using a low-energy precipitation method. Following experimental optimisation for particle characteristics and encapsulation efficiency, nanoparticles were further embedded into a Carbopol-xanthan gum hydrogel. Characteristic results of BA-NPs, including size (174 ± 2.1 nm), PDI (0.25), ζ-potential (− 30.01 mV), and high entrapment efficiency (up to 69.6 ± 1.1%), were confirmed. Antioxidant efficacy was assessed in vitro in RAW264.7 cells, while ex vivo skin permeation determined Cskinmax and AUC. Stability was monitored for 90 days under multiple storage conditions, with the aim of predicting extended shelf life. Optimised BA-NP-G maintained chemical stability and > 90% drug content for up to one year at 4 °C. Ex vivo skin permeation studies revealed a ~ 3-fold increase in epidermal drug deposition and ~ 2.5-fold increase in total skin AUC in drug delivery for BA-NP-G when compared against BA solution, with notably higher Cskinmax and AUC values. Cellular response studies and antioxidant assays demonstrated superior free-radical scavenging activity when BA was encapsulated in NPs using RO as the liquid lipid, confirming a robust synergistic effect that markedly exceeded the activity of individual components. The BA-NP-G developed here combines the properties of both BA and RO, forming a synergistic blend within a nano-phytogel matrix to achieve significantly improved physical stability, enhanced skin bioavailability, and increased biological efficacy.