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王文鹏, 施丹, 李明锐.pH响应型芹菜素纳米颗粒靶向溃疡性结肠炎的增效研究[J].湖南中医药大学学报,2026,46(8):1535-1547[点击复制] |
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| pH响应型芹菜素纳米颗粒靶向溃疡性结肠炎的增效研究 |
| 王文鹏,施丹,李明锐 |
| (天津医科大学肿瘤医院, 国家肿瘤临床医学研究中心, 天津市恶性肿瘤临床医学研究中心, 天津市肿瘤防治重点实验室, 天津 300060;德国埃尔朗根-纽伦堡大学库斯毛尔医学研究园区, 巴伐利亚州 埃尔朗根 91052;天津医科大学南开临床学院, 天津市急腹症器官损伤与中西医修复重点实验室, 天津市中西医结合急腹症研究所, 天津 300100;达州市中心医院, 四川 达州 635000) |
| 摘要: |
| 目的 通过纳米技术改良芹菜素的递送系统，并评估其在溃疡性结肠炎（UC）治疗中的潜在疗效。方法 采用纳米沉淀法制备载芹菜素的聚乳酸-羟基乙酸共聚物（PLGA）纳米颗粒（PANPs）和PLGA联合pH敏感聚合物（ES100）复合纳米颗粒（PEANPs），并通过粒径、多分散性指数（PDI）、Zeta电位、包封率、扫描电子显微镜及体外释放实验对其理化性质进行表征。采用MTT、Transwell及共聚焦显微镜评价其细胞毒性、跨上皮渗透和细胞内化能力。建立��唑酮和硫酸葡聚糖钠盐（DSS）诱导的急性UC小鼠模型，通过内镜、活性成像系统（IVIS）-过氧化物酶（MPO）活性成像、组织病理学、MPO免疫荧光、RT-qPCR和ELISA评价其抗炎作用，并采用IVIS和共聚焦显微镜观察纳米制剂在结肠组织中的分布与定位。结果 成功制备了PANPs和PEANPs。与游离芹菜素相比，两种纳米颗粒的粒径均减小（P<0.001），PDI降低（P<0.001），PEANPs的Zeta电位负值最大（P<0.01）；PANPs和PEANPs的包封率分别为93.0%±3.0%和89.0%±3.5%。体外实验表明，与游离芹菜素相比，两种纳米颗粒均可跨越Caco-2细胞形成的致密肠上皮屏障，并能有效穿透SW480细胞质膜。体内实验进一步证实，与安慰剂组相比，PANPs和PEANPs均可显著改善��唑酮和DSS诱导的急性UC小鼠的疾病表型及炎症相关指标（P<0.05），并可在炎症结肠组织中形成较明显的荧光信号富集（P<0.05）。结论 本研究构建的PANPs和PEANPs能有效增强药物对肠屏障的穿透能力和病灶靶向性，显著提升其在UC模型中的抗炎疗效，展现出良好的治疗潜力。 |
| 关键词: 溃疡性结肠炎|芹菜素|纳米颗粒|pH敏感聚合物|聚乳酸-羟基乙酸共聚物 |
| DOI：10.3969/j.issn.1674-070X.2026.08.001 |
| 投稿时间：2026-01-25 |
| 基金项目:国家卫生健康委员会慢病管理基金项目（GWJJMB202510024049）；天津市医学重点学科（专科）建设项目（TJYXZDXK-009A）；河北省中医药管理局科研计划项目（T2026068）。 |
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| Synergistic effects of pH-responsive apigenin nanoparticles for targeted therapy of ulcerative colitis |
| WANG Wenpeng, SHI Dan, LI Mingrui |
| (Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Treatment, Tianjin 300060, China;Kussmaul Campus for Medical Research, University of Erlangen-Nürnberg, Erlangen, Bavaria 91052, Germany;Nankai Clinical Hospital of Tianjin Medical University, Tianjin Key Laboratory of Acute Abdomen Disease-Associated Organ Injury and ITCWM Repair, Tianjin Institute of Integrated Chinese and Western Medicine for Acute Abdominal Diseases, Tianjin 300100, China;Dazhou Central Hospital, Dazhou, Sichuan 635000, China) |
| Abstract: |
| Objective To develop the delivery system of apigenin using nanotechnology and evaluate its potential therapeutic efficacy in ulcerative colitis (UC). Methods Apigenin-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles (PANPs) and PLGA/pH-sensitive polymer (ES100) composite nanoparticles (PEANPs) were prepared by nanoprecipitation. Their physicochemical properties were characterized in terms of particle size, polydispersity index (PDI), zeta potential, encapsulation efficiency, scanning electron microscopy, and in vitro release assays. MTT assay, Transwell assay, and confocal microscopy were employed to evaluate cytotoxicity, transepithelial permeability, and cellular internalization. Mouse models with acute UC induced by oxazolone and dextran sulfate sodium (DSS) were established. The anti-inflammatory effects of the nanoformulations were evaluated by endoscopy, in vivo imaging system (IVIS)-based myeloperoxidase (MPO) activity imaging, histopathological examination, MPO immunofluorescence staining, reverse transcription quantitative polymerase chain reaction (RT-qPCR), and ELISA. IVIS and confocal microscopy were used to observe the distribution and localization of the nanoformulations in colonic tissues. Results PANPs and PEANPs were successfully prepared. Compared with free apigenin, both nanoparticles exhibited significantly reduced particle size (P<0.001) and lower PDI (P<0.001), while PEANPs showed the most negative zeta potential (P<0.01). Encapsulation efficiencies of PANPs and PEANPs were 93.0%±3.0% and 89.0%±3.5%, respectively. In vitro assays showed that, compared with free apigenin, both nanoparticles could traverse the tight intestinal epithelial barrier formed by Caco-2 cells and effectively penetrate the plasma membrane of SW480 cells. In vivo experiments further confirmed that, compared with the placebo group, both PANPs and PEANPs significantly ameliorated disease phenotypes and inflammation-related indicators in mice with oxazolone- and DSS-induced acute UC (P<0.05), and exhibited more pronounced accumulation of fluorescent signals in inflamed colonic tissues (P<0.05). Conclusion PANPs and PEANPs developed in this study can effectively enhance intestinal-barrier penetration and lesion-targeting ability of apigenin, and significantly improve anti-inflammatory efficacy in UC models, thereby exhibiting promising therapeutic potential. |
| Key words: ulcerative colitis|apigenin|nanoparticles|pH-sensitive polymer|poly(lactic-co-glycolic acid) |
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