Pharmacological Potentials and Delivery Strategies of Isoliquiritigenin: Challenges and Advances in Enhancing...

Isoliquiritigenin (ISLT), a bioactive and typical chalcones ingredient isolated from the root of licorice, has shown various pharmacological properties, including antitumor, anti-inflammatory and antioxidant activities. It is extensively utilized in the management of tumors, diabetes mellitus, dermatological disorders, and other therapeutic applications. Although ISLT has been globally recognized for its health benefits, its oral administration is still restricted by sparing water solubility, poor bioavailability, and slow dissolution in the intestine. For topical application, deficiencies include poor transdermal absorption and low skin permeability. Therefore, optimizing drug delivery systems and improving its bioavailability are considered a productive platform to solve these challenges of ISLT, but detailed strategies have not yet been systematically organized. This review first comprehensively summarizes the pharmacological activities, inherent mechanisms and therapeutic potentials of ISLT. Next, it describes programs to improve permeability and bioavailability in oral and transdermal drug delivery, such as nanocomposites, nanoemulsions, cyclodextrin complexes, and exosomes, as well as the use of chemical permeation enhancers. The applications of multiple administration routes and different formulations for enhanced bioavailability are exclusively compared. Additionally, new solutions such as ISLT derivatives and exosomes were proposed, aiming to address the limitations of ISLT and providing new ideas for its further application. In summary, this review offers comprehensive reference and theoretical support for the optimization and enhancement of the bioavailability for other natural flavonoid ingredients.