As the principal active ingredient of Scutellaria baicalensis Georgi, Baicalin demonstrates anti-inflammatory and neuroprotective activities with the potential to repair brain injury. Nonetheless, poor solubility in water and low bioavailability of Ba limits its clinical application. To enhance solubility, bioavailability, and lesion-site delivery of Ba to reactive oxygen species (ROS)-rich lesions, we developed a ROS-responsive liposomal delivery system using DSPE-SS-PEG. Thin-film hydration was utilized to prepare the Ba-loaded liposomes (Ba@DSPE-SS-PEG-Liposome), before optimization via response surface methodology. The liposomes were comprehensively characterized in vitro using drug loading, particle size, morphology, release behavior, and encapsulation efficiency. Under high ROS conditions, internalization of ROS-responsive (DSPE-SS-PEG-modified) formulation was improved based on findings of cellular uptake studies. At the ischemic site, liposomes promoted targeted accumulation and prolonged systemic circulation of the drug. Neurological deficits, cerebral edema, and neuronal apoptosis were significantly alleviated in a rat model of hemorrhagic stroke by the ROS-responsive liposomes, which outperformed conventional liposomes and free Ba. Synergistic regulation of inflammatory and oxidative stress pathways mediated these therapeutic benefits. Altogether, the therapeutic efficacy of BA in hemorrhagic stroke can be effectively enhanced by this ROS-responsive (stimuli-responsive) liposomal system.
Luo et al. (2026) studied this question.