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<p>Coronary microcirculatory dysfunction, affecting over half of acute myocardial infarction (AMI) patients, correlates significantly with AMI prognosis. Nicorandil is an effective drug that markedly improves coronary microcirculation, but current clinical formulations of Nicorandil exhibit a relatively short half-life and lack cardiac selectivity. We formulated and synthesized a variety of mesoporous silica nanoparticles (MSNs) as a drug carrier for loading and delivering Nicorandil. We performed PEG modification on MSNs to enhance their biocompatibility. The SiO<sub>2</sub>@PEG showed good serum stability, maintained a uniform spherical structure with a particle size distribution centered within 200&#xa0;nm and exhibits good dispersibility. SiO<sub>2</sub>@PEG-Nicorandil showed no significant impact on AC 16 cells’ viability at concentrations up to 50&#xa0;µg/mL. SiO<sub>2</sub>@PEG-Nicorandil significantly enhanced the viability of AC16 cells under oxidative stress conditions, while concurrently reducing intracellular levels of reactive oxygen species (ROS) and Ca²⁺. For the rat coronary microvascular dysfunction model, the SiO<sub>2</sub>@PEG-Nicorandil group demonstrated a greater decrease in thrombus formation and the expression of inflammatory cytokines, outperforming the Nicorandil group. In vivo imaging revealed that within one hour post-injection of SiO<sub>2</sub>@PEG-Nicorandil-CY7, a notable increase in CY7 fluorescence intensity was observed in the cardiac region compared to surrounding tissues. Drug concentration measurements demonstrated that Nicorandil maintained a stable concentration in cardiac blood at 48&#xa0;h in the SiO<sub>2</sub>@PEG-Nicorandil group. Taken together, SiO<sub>2</sub>@PEG-Nicorandil had exhibited superior cardiac-targeting capabilities and sustained-release properties. Within a specific concentration range, it demonstrated enhanced therapeutic effects in the treatment of coronary microcirculation disorders in rats when compared to conventional Nicorandil formulations.</p>

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Improvement of coronary microcirculation in acute myocardial ischemia rats using a nanoscale carrier SiO2@PEG loaded with Nicorandil

  • 期刊论文

  • 发表日期：

    2025年3月7日

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  • Rui Wang,
  • Yujing Mo,
  • Yingcong Liang,
  • Yuanhui Liu,
  • Zhongchan Sun,
  • Wenting Shang,
  • Ling Xue

摘要

Coronary microcirculatory dysfunction, affecting over half of acute myocardial infarction (AMI) patients, correlates significantly with AMI prognosis. Nicorandil is an effective drug that markedly improves coronary microcirculation, but current clinical formulations of Nicorandil exhibit a relatively short half-life and lack cardiac selectivity. We formulated and synthesized a variety of mesoporous silica nanoparticles (MSNs) as a drug carrier for loading and delivering Nicorandil. We performed PEG modification on MSNs to enhance their biocompatibility. The SiO2@PEG showed good serum stability, maintained a uniform spherical structure with a particle size distribution centered within 200 nm and exhibits good dispersibility. SiO2@PEG-Nicorandil showed no significant impact on AC 16 cells’ viability at concentrations up to 50 µg/mL. SiO2@PEG-Nicorandil significantly enhanced the viability of AC16 cells under oxidative stress conditions, while concurrently reducing intracellular levels of reactive oxygen species (ROS) and Ca²⁺. For the rat coronary microvascular dysfunction model, the SiO2@PEG-Nicorandil group demonstrated a greater decrease in thrombus formation and the expression of inflammatory cytokines, outperforming the Nicorandil group. In vivo imaging revealed that within one hour post-injection of SiO2@PEG-Nicorandil-CY7, a notable increase in CY7 fluorescence intensity was observed in the cardiac region compared to surrounding tissues. Drug concentration measurements demonstrated that Nicorandil maintained a stable concentration in cardiac blood at 48 h in the SiO2@PEG-Nicorandil group. Taken together, SiO2@PEG-Nicorandil had exhibited superior cardiac-targeting capabilities and sustained-release properties. Within a specific concentration range, it demonstrated enhanced therapeutic effects in the treatment of coronary microcirculation disorders in rats when compared to conventional Nicorandil formulations.