Liposomal formulation improves the bioactivity of usnic acid in RAW264.7 macrophage cells reducing its toxicity

Background: Reactive oxygen species (ROS) production and oxidative stress may be responsible for the onset of several chronic diseases. Usnic acid (UA) is a natural secondary metabolite of lichens with several healthful bioactivities, including antioxidant properties. However, UA is a hydrophobic compound known for its hepatic toxicity. These aspects limit its therapeutic applications. To overcome these drawbacks and improve the pharmacological use of hydrophobic compounds, nanotechnology is widely used. Therefore, the incorporation of UA into appropriate nanocarriers could enhance the bioactivity of UA by increasing its solubility. Objective: The aim of this work was to improve the solubility of UA and its bioactivity in the absence of cytotoxicity. Methods: In this study, UA loaded liposomes (UA-LP) were developed. The formulations were chemically and physically characterized, and an in vitro release study was performed. Free UA and UA-LP were tested on RAW 264.7 murine macrophages in terms of cytotoxicity, intracellular ROS production, and NO release in the absence or presence of pro-oxidant LPS stimulus. Results: UA-LP showed excellent physical and chemical stability during storage and improved solubility of UA. UA-LP showed an antioxidant effect in the absence of cytotoxicity compared with free UA on LPS-exposed macrophages. Conclusion: For the first time, liposomal formulation improved the beneficial action of UA in terms of solubility and antioxidant activity.