Abstract 6239: A novel topical delivery system of carvedilol for skin cancer prevention
| Autor: | Mengbing Chen, Kaitlyn Coronel, Ying Huang, Ayaz Shahid, Abdullah Shamim, Steven Yeung, Bradley T. Andresen, Jeffrey Wang |
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| Rok vydání: | 2020 |
| Předmět: | |
| Zdroj: | Cancer Research. 80:6239-6239 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | Solar ultraviolet (UV) light-induced non-melanoma skin cancer is the most common type of cancer diagnosed in the United States and remains one of the major public health concerns. There is an urgent need to develop effective and safe skin cancer chemopreventive agents. We have previously demonstrated that carvedilol, an FDA approved β-blocker for cardiovascular diseases, could prevent UV-induced skin cancer 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. In this study, we designed a novel topical formulation, namely carvedilol-loaded transfersomes (T-CAR), to maintain cancer preventive properties of carvedilol while avoiding systemic cardiovascular effects. T-CAR formulations were prepared using different phospholipids and surfactants at various ratios by the thin-film hydration method. The formulations were characterized in terms of particle size, zeta potential, and encapsulation efficiency. An optimal formulation was identified that composes carvedilol, soy phosphatidylcholine (SPC), and Tween 80 at a ratio of 1:3:0.5 with the particle size of 95.84 ± 3.8 nm, the zeta potential of +11.34 ± 0.7 mV, and the encapsulation efficiency of 93.7 ± 5.1%. The in vitro drug release and ex vivo skin permeation studies were performed using Pur-A-Lyzer mini dialysis kit and Franz diffusion cells, respectively. The optimal formulation showed a relative slow in vitro release profile and it could permeate through the porcine ear skin to the same degree as free carvedilol dissolved in acetone. 200 uL of 10 uM carvedilol dissolved in acetone, T-CAR containing the same amount of carvedilol as in acetone group, or the plain transfersome were topically applied to SKH-1 hairless mice 30 minutes before and immediately after single-dose UV irradiation. Compared to carvedilol solution, T-CAR demonstrated the same inhibitory effects against UV-induced epidermis thickening but exhibited increased inhibitory effects against UV-induced cyclobutane pyrimidine dimer (CPD) formation and mRNA expression of pro-inflammatory cytokines IL-1β and IL-6. In addition, carvedilol was not detectable by LC-MS in plasma after topical administration. These findings suggest that T-CAR could be a promising topical carvedilol formulation to prevent UV-associated skin cancer, with enhanced photoprotective effects but neglectable systemic cardiovascular effects. Citation Format: Mengbing Chen, Steven Yeung, Md Abdullah Shamim, Kaitlyn Coronel, Ayaz Shahid, Bradley Andresen, Jeffrey Wang, Ying Huang. A novel topical delivery system of carvedilol for skin cancer prevention [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6239. |
| Databáze: | OpenAIRE |
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