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

IF 5.7 3区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Drug Delivery and Translational Research Pub Date : 2025-03-07 DOI:10.1007/s13346-025-01820-0

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

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Abstract

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.

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纳米级载体SiO2@PEG负载尼可地尔改善急性心肌缺血大鼠冠状动脉微循环。

冠状动脉微循环功能障碍影响半数以上的急性心肌梗死（AMI）患者，与AMI预后显著相关。尼可地尔是一种显著改善冠状动脉微循环的有效药物，但目前临床配方的尼可地尔半衰期相对较短，缺乏心脏选择性。我们配制并合成了多种介孔二氧化硅纳米颗粒（MSNs）作为药物载体，用于装载和递送尼可地尔。我们对msn进行PEG修饰以增强其生物相容性。SiO2@PEG具有良好的血清稳定性，保持均匀的球形结构，粒径分布以200 nm为中心，具有良好的分散性。SiO2@PEG-Nicorandil在浓度高达50µg/mL时对AC 16细胞的活力没有显著影响。SiO2@PEG-Nicorandil显著提高了氧化应激条件下AC16细胞的活力，同时降低了细胞内活性氧（ROS）和Ca 2 +的水平。对于大鼠冠状动脉微血管功能障碍模型，SiO2@PEG-Nicorandil组血栓形成和炎症细胞因子的表达均明显降低，优于Nicorandil组。体内成像显示，注射SiO2@PEG-Nicorandil-CY7后1小时内，心脏区域CY7荧光强度较周围组织明显增加。药物浓度测量表明，SiO2@PEG-Nicorandil组48小时内尼可地尔在心脏血液中保持稳定浓度。综上所述，SiO2@PEG-Nicorandil表现出优越的心脏靶向能力和持续释放特性。在特定的浓度范围内，与传统的尼可地尔制剂相比，它在治疗大鼠冠状动脉微循环疾病方面表现出增强的治疗效果。

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来源期刊

Drug Delivery and Translational Research MEDICINE, RESEARCH & EXPERIMENTALPHARMACOL-PHARMACOLOGY & PHARMACY

CiteScore

11.70

自引率

1.90%

发文量

160

期刊介绍： The journal provides a unique forum for scientific publication of high-quality research that is exclusively focused on translational aspects of drug delivery. Rationally developed, effective delivery systems can potentially affect clinical outcome in different disease conditions. Research focused on the following areas of translational drug delivery research will be considered for publication in the journal. Designing and developing novel drug delivery systems, with a focus on their application to disease conditions; Preclinical and clinical data related to drug delivery systems; Drug distribution, pharmacokinetics, clearance, with drug delivery systems as compared to traditional dosing to demonstrate beneficial outcomes Short-term and long-term biocompatibility of drug delivery systems, host response; Biomaterials with growth factors for stem-cell differentiation in regenerative medicine and tissue engineering; Image-guided drug therapy, Nanomedicine; Devices for drug delivery and drug/device combination products. In addition to original full-length papers, communications, and reviews, the journal includes editorials, reports of future meetings, research highlights, and announcements pertaining to the activities of the Controlled Release Society.