Changcan Shi1, Hongjuan Wu2, Ke Xu3, Ting Cai3, Kunming Qin4, Li Wu1, Baochang Cai1,4. 1. School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210046, People's Republic of China. 2. Nanjing Jiangning District Hospital of Traditional Chinese Medicine, Nanjing 211100, People's Republic of China. 3. School of Pharmacy, China Pharmaceutical University, Nanjing 210009, People's Republic of China. 4. Nanjing Haichang Chinese Medicine Group Corporation, Nanjing 210061, People's Republic of China.
Abstract
BACKGROUND: The clinical use of doxorubicin (DOX) is severely limited due to its cardiotoxicity. Thus, there is a need for prophylactic and treatment strategies against DOX-induced cardiotoxicity. PURPOSE: The purpose of this study was to develop a liquiritigenin-loaded submicron emulsion (Lq-SE) with enhanced oral bioavailability and to explore its efficacy against DOX-induced cardiotoxicity. METHODS: Lq-SE was prepared using high-pressure homogenization and characterized using several analytical techniques. The formulation was optimized by central composite design response surface methodology (CCD-RSM). In vivo pharmacokinetic studies, biochemical analyses, reactive oxygen species (ROS) assays, histopathologic assays, and Western blot analyses were performed. RESULTS: Each Lq-SE droplet had a mean particle size of 221.7 ± 5.80 nm, a polydispersity index (PDI) of 0.106 ± 0.068 and a zeta potential of -28.23 ± 0.42 mV. The area under the curve (AUC) of Lq-SE was 595% higher than that of liquiritigenin (Lq). Lq-SE decreased the release of serum cardiac enzymes and ameliorated histopathological changes in the hearts of DOX-challenged mice. Lq-SE significantly reduced oxidative stress by adjusting the levels of ROS, increasing the activity of antioxidative enzymes and inhibiting the protein expression of NOX4 and NOX2. Furthermore, Lq-SE significantly improved the inflammatory response through the mitogen-activated protein kinase (MAPK)/nuclear factor-κB (NF-κB) signalling pathway and induced cardiomyocyte apoptosis. CONCLUSION: Lq-SE could be used as an effective cardioprotective agent against DOX in chemotherapy to enable better treatment outcomes.
BACKGROUND: The clinical use of doxorubicin (DOX) is severely limited due to its cardiotoxicity. Thus, there is a need for prophylactic and treatment strategies against DOX-induced cardiotoxicity. PURPOSE: The purpose of this study was to develop a liquiritigenin-loaded submicron emulsion (Lq-SE) with enhanced oral bioavailability and to explore its efficacy against DOX-induced cardiotoxicity. METHODS: Lq-SE was prepared using high-pressure homogenization and characterized using several analytical techniques. The formulation was optimized by central composite design response surface methodology (CCD-RSM). In vivo pharmacokinetic studies, biochemical analyses, reactive oxygen species (ROS) assays, histopathologic assays, and Western blot analyses were performed. RESULTS: Each Lq-SE droplet had a mean particle size of 221.7 ± 5.80 nm, a polydispersity index (PDI) of 0.106 ± 0.068 and a zeta potential of -28.23 ± 0.42 mV. The area under the curve (AUC) of Lq-SE was 595% higher than that of liquiritigenin (Lq). Lq-SE decreased the release of serum cardiac enzymes and ameliorated histopathological changes in the hearts of DOX-challenged mice. Lq-SE significantly reduced oxidative stress by adjusting the levels of ROS, increasing the activity of antioxidative enzymes and inhibiting the protein expression of NOX4 and NOX2. Furthermore, Lq-SE significantly improved the inflammatory response through the mitogen-activated protein kinase (MAPK)/nuclear factor-κB (NF-κB) signalling pathway and induced cardiomyocyte apoptosis. CONCLUSION: Lq-SE could be used as an effective cardioprotective agent against DOX in chemotherapy to enable better treatment outcomes.
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