Development of optimized resveratrol/piperine-loaded phytosomal nanocomplex for isoproterenol-induced myocardial infarction treatment

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 � (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 (<i>p</i> &lt; 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 (&gt;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.