International journal of nanomedicine · 2026
Surface-Engineered Breviscapine Nanocrystals for Enhanced Oral Absorption and Cardioprotection in Isoprenaline-Induced Myocardial Infarction.
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Li Fang, Yue Pengfei, Liu Yuling, Chen Liru, Hu Wenhui, Zou Haibin, Yu Quanda, Shi Wenli, Chen Yingchong
Аннотация
PURPOSE: Breviscapine (BRE) possesses excellent cardioprotective efficacy against myocardial infarction (MI). However, its oral application is severely hindered by BCS Class IV properties, including poor solubility and permeability, accompanied by P-glycoprotein (P-gp)-mediated drug efflux and gastrointestinal absorption barriers. Arginine-rich CPPs such as R8 can promote cellular uptake, whereas cationic surface characteristics may restrict particle mobility in gastrointestinal mucus. Conversely, hydrophilic and electro-neutral surfaces favor mucus penetration but may reduce epithelial uptake. This imposes challenges for balancing these two absorption barriers. To solve these problems, we developed surface-engineered nanocrystals with sequential barrier-crossing capability (R8-F127-VES@BRE-NCs).
METHODS: We engineered multifunctional nanocrystals (R8-F127-VES@BRE-NCs) featuring a sequential barrier-crossing design: nanocrystal technology increases saturation solubility, Pluronic F127 imparts mucus-penetrating capability, R8 peptide facilitates epithelial internalization, and Vitamin E Succinate (VES) may contribute to efflux modulation.
RESULTS: Comprehensive characterization and in vitro studies suggested that this integrated design helped address the trade-off between mucus diffusion and epithelial uptake. Pharmacokinetic studies revealed a marked enhancement in oral BRE absorption, with Cmax and AUC0-∞ increased to 185.76 ng/mL and 1418.34 ng·mL-1·h (4.27- and 7.37-fold over BRE-raw). Following establishment of the isoprenaline-induced myocardial injury model, 14-day oral treatment with R8-F127-VES@BRE-NCs showed enhanced cardioprotective effects, as evidenced by reduced infarct size and improved oxidative stress-related biochemical indicators.
CONCLUSION: R8-F127-VES-modified nanocrystals provide a promising strategy for overcoming oral delivery barriers and enhancing the cardioprotective effects of orally administered BRE.
METHODS: We engineered multifunctional nanocrystals (R8-F127-VES@BRE-NCs) featuring a sequential barrier-crossing design: nanocrystal technology increases saturation solubility, Pluronic F127 imparts mucus-penetrating capability, R8 peptide facilitates epithelial internalization, and Vitamin E Succinate (VES) may contribute to efflux modulation.
RESULTS: Comprehensive characterization and in vitro studies suggested that this integrated design helped address the trade-off between mucus diffusion and epithelial uptake. Pharmacokinetic studies revealed a marked enhancement in oral BRE absorption, with Cmax and AUC0-∞ increased to 185.76 ng/mL and 1418.34 ng·mL-1·h (4.27- and 7.37-fold over BRE-raw). Following establishment of the isoprenaline-induced myocardial injury model, 14-day oral treatment with R8-F127-VES@BRE-NCs showed enhanced cardioprotective effects, as evidenced by reduced infarct size and improved oxidative stress-related biochemical indicators.
CONCLUSION: R8-F127-VES-modified nanocrystals provide a promising strategy for overcoming oral delivery barriers and enhancing the cardioprotective effects of orally administered BRE.