Triptolide (TPL) is a natural compound and active component of Tripterygium wilfordii Hook F., an Asian native woody vine widely used for over 200 years in Chinese medicine. Hot water, ethanol-ethyl acetate, and chloroform-methanol extracts are the first reported TPL preparations in the literature, and since then, several studies for application in inflammation processes and cancer are described due to the antitumor, anti-inflammatory, and immunosuppressive characteristics of the molecule. However, physicochemical properties such as poor solubility and bioavailability are the main concerns regarding the TPL safety and efficacy in clinical studies since trials have reported adverse side effects alongside the excellent TPL therapeutic effects. Here, we review the main TPL applications and issues related to the drug usage, and a comprehensive summary of diseases is provided. Special emphasis is given to drug delivery systems designed to overcome the TPL physicochemical characteristics such as poor drug solubility, and how to increase efficacy and obtain a safe drug profile. Graphical abstract.
Keywords: Cancer therapy; Drug delivery systems; Psoriasis; Rheumatoid arthritis; Tripterygium wilfordii; Triptolide.