{"title":"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。","authors":"Rui Wang, Yujing Mo, Yingcong Liang, Yuanhui Liu, Zhongchan Sun, Wenting Shang, Ling Xue","doi":"10.1007/s13346-025-01820-0","DOIUrl":null,"url":null,"abstract":"<p><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 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 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 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>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.7000,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Improvement of coronary microcirculation in acute myocardial ischemia rats using a nanoscale carrier SiO<sub>2</sub>@PEG loaded with Nicorandil.\",\"authors\":\"Rui Wang, Yujing Mo, Yingcong Liang, Yuanhui Liu, Zhongchan Sun, Wenting Shang, Ling Xue\",\"doi\":\"10.1007/s13346-025-01820-0\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><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 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 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 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>\",\"PeriodicalId\":11357,\"journal\":{\"name\":\"Drug Delivery and Translational Research\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":5.7000,\"publicationDate\":\"2025-03-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Drug Delivery and Translational Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s13346-025-01820-0\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Drug Delivery and Translational Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s13346-025-01820-0","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
Improvement of coronary microcirculation in acute myocardial ischemia rats using a nanoscale carrier SiO2@PEG loaded with Nicorandil.
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.
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.
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