Freeze-Dried Softisan® 649-Based Lipid Nanoparticles for Enhanced Skin Delivery of Cyclosporine A
Maria Inês Silva, Ana Isabel Barbosa, Sofia A. Costa Lima, Paulo Costa, Tiago Torres, Salette Reis
Abstract
Inflammatory skin diseases, including psoriasis and atopic dermatitis, affect around one quarter to one third of the world population. Systemic cyclosporine A, an immunosuppressant agent, is included in the current therapeutic armamentarium of these diseases. Despite being highly effective, it is associated with several side effects, and its topical administration is limited by its high molecular weight and poor water solubility. To overcome these limitations, cyclosporine A was incorporated into solid lipid nanoparticles obtained from Softisan® 649, a commonly used cosmetic ingredient, aiming to develop a vehicle for application to the skin. The nanoparticles presented sizes of around 200 nm, low polydispersity, negative surface charge, and stability when stored for 8 weeks at room temperature or 4 °C. An effective incorporation of 88% of cyclosporine A within the nanoparticles was observed, without affecting its morphology. After the freeze-drying process, the Softisan® 649-based nanoparticles formed an oleogel. Skin permeation studies using pig ear as a model revealed low permeation of the applied cyclosporine A in the freeze-dried form of the nanoparticles in relation to free drug and the freshly prepared nanoparticles. About 1.0 mg of cyclosporine A was delivered to the skin with reduced transdermal permeation. These results confirm local delivery of cyclosporine A, indicating its promising topical administration.