Surface-Engineered Breviscapine Nanocrystals for Enhanced Oral Absorption and Cardioprotection in Isoprenaline-Induced Myocardial Infarction

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).