Abstract 2176: Topical delivery of carvedilol-loaded transfersomes for photoprotection and skin cancer prevention

Abstract

Abstract Ultraviolet (UV)-induced skin cancer is the most common cancer diagnosed in the United States and remains one of major public health concerns. Thus, there is an urgent need for the development of more effective strategies to prevent and treat skin cancer. We have previously demonstrated that carvedilol, an FDA approved β-blocker for cardiovascular diseases, could prevent UV-induced skin cancer both in vitro and in vivo. However, the β-adrenergic blockade effects of carvedilol might be a barrier for its repurposing as a cancer chemopreventive agent due to its cardiovascular side effects. In this work, we aimed to design a novel topical formulation, namely carvedilol-loaded transfersomes, which could maintain anti-cancer activities but avoid systemic cardiovascular effects. Carvedilol-loaded transfersomes were prepared using different phospholipids and surfactants at various ratios by a thin-film hydration method. Following optimization of preparation, the transfersomes were characterized in terms of particle size, zeta potential, and encapsulation efficiency. Skin permeation studies were performed using Franz vertical diffusion cells and skin dissected from SKH-1 hairless mice to examine the permeability of carvedilol. An optimal formulation was identified to compose carvedilol, Soy PC, and Tween-80 at a ratio of 1:3:0.5. The particle size, zeta potential and encapsulation efficiency for this formulation were determined to be 162.9±9.6 nm, 17.1±0.3 mV and 47.9±3.5%, respectively. Skin permeation studies showed that the specific carvedilol-loaded transfersomes could not penetrate through the skin layers in comparison with free carvedilol dissolved in acetone. Taken together, these results suggest that the transfersomal formulations of carvedilol may have desirable physical and biological characteristics for skin retention and local action. Ongoing studies are focused on further improvement of encapsulation efficiency and determination of its effectiveness against skin cancer. Citation Format: Mengbing Chen, Mengbing Chen. Topical delivery of carvedilol-loaded transfersomes for photoprotection and skin cancer prevention [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2176.