Abstract：
Cardiovascular disease is a significant and ever-growing concern, causing high morbidity and mortality worldwide. Conventional therapy is often very precarious and requires long-term usage. Several phytochemicals, including Resveratrol (RSV) and Piperine (PIP), possess significant cardioprotection and may be restrained in clinical settings due to inadequate pharmacokinetic properties. Therefore, this study strives to develop an optimized RSV phytosomes (RSVP) and RSV phytosomes co-loaded with PIP (RPP) via solvent evaporation method using Box-Behnken design to enhance the pharmacokinetic properties in isoproterenol-induced myocardial infarction (MI). The optimized particle size (20.976 ± 0.39 and 176.53 ± 0.88 nm), zeta potential (-33.33 ± 1.5 and -48.7 ± 1.6 mV), drug content (84.57 ± 0.9 and 87.16 ± 0.6%), and %EE (70.56 ± 0.7 and 67.60 ± 0.57%) of the prepared RSVP and RPP, respectively demonstrated enhanced solubility and control release in diffusion media. The oral administration of optimized RSVP and RPP in myocardial infarction-induced rats exhibited significant (p < 0.001) improvement in heart rate, ECG, biomarker, anti-oxidant levels, and no inflammation than pure RSV. The pharmacokinetic assessment on healthy Wistar rats exhibited prolonged circulation (>24 h) of RSVP and RPP compared to free drug/s. The enhanced ability of RSVP and RPP to penetrate bio-membranes and enter the systemic circulation renders them a more promising strategy for mitigating MI.
摘要：
心血管疾病是一个重要且日益增长的问题，在世界范围内造成高发病率和死亡率。常规疗法通常非常不稳定，需要长期使用。几种植物化学物质，包括白藜芦醇（RSV）和胡椒碱（PIP），具有显着的心脏保护作用，并且由于药代动力学特性不足，可能在临床环境中受到限制。因此,本研究致力于使用Box-Behnken设计通过溶剂蒸发方法开发优化的RSV植物体（RSVP）和RSV植物体与PIP（RPP）共负载，以增强异丙肾上腺素诱导的心肌梗死（MI）的药代动力学特性。优化的粒径（20.976±0.39和176.53±0.88nm），zeta电位（-33.33±1.5和-48.7±1.6mV），药物含量（84.57±0.9和87.16±0.6%），和制备的RSVP和RPP的%EE(70.56±0.7和67.60±0.57%)，分别证明了在扩散介质中增强的溶解度和控制释放。在心肌梗死诱导的大鼠中口服优化的RSVP和RPP表现出显著(p<0.001)的心率改善,心电图,生物标志物，抗氧化剂水平，和没有炎症比纯RSV。与游离药物/s相比，健康Wistar大鼠的药代动力学评估显示RSVP和RPP的循环延长（>24小时）。RSVP和RPP穿透生物膜并进入体循环的增强能力使其成为减轻MI的更有希望的策略。
