Development of lipid nanoparticles containing the xanthone LEM2 for topical treatment of melanoma

• Published in: Journal of drug delivery science and technology Vol. 61; p. 102226
• Main Authors: Malta, Rafaela, Loureiro, Joana B., Costa, Paulo, Sousa, Emília, Pinto, Madalena, Saraiva, Lucília, Amaral, M. Helena
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.02.2021
• Subjects: LEM2; Lipid nanoparticles; Melanoma; Skin cancer; Topical anticancer therapy; Topical anticancer therapy; LEM2; Lipid nanoparticles; Melanoma; Skin cancer
• ISSN: 1773-2247
• DOI: 10.1016/j.jddst.2020.102226

Melanoma is the most aggressive form of skin cancer. Thus, it is important to improve skin cancer treatment efficacy. Topical treatment of skin diseases is a worthy strategy since avoids systemic side effects commonly associated with oral and parenteral drugs administration. The 1-carbaldehyde-3,4-dimethoxyxanthone (LEM2), previously reported as a TAp73 activator, has potent antiproliferative effect on melanoma A375 cell lines. However, it presents poor aqueous solubility and poor bioavailability. Thus, the use of lipid nanoparticles to encapsulate LEM2 seems to be a promising strategy for topical delivery of this drug. In this work, unloaded nanostructured lipid carriers (NLCs) were obtained by hot high-pressure homogenization (HPH) and ultrasonication. These lipid nanoparticles were characterized, and stability tests were performed for 60 days. NLCs were stable and ultrasonication showed to be an easier method to prepare these nanoparticles when compared to hot HPH. Thus, LEM2 was encapsulated in NLCs, using the ultrasonication method, and the final loaded NLCs had a mean particle size suitable for topical application and a high encapsulation efficiency. This formulation seemed to be more cytotoxic against melanoma A375 cell line than unloaded NLCs, which indicates the potential use of NLCs as a carrier to LEM2, improving its efficacy. [Display omitted]