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投稿时间：2021-12-08 网络发布日期：2022-05-20
投稿时间：2021-12-08 网络发布日期：2022-05-20
中文摘要: 目的 设计制备搭载麦醇溶蛋白（Gliadin）-雷帕霉素（Rapamycin，Rapa）的复合纳米颗粒，经结构表征、稳定性、缓释特性等研究优选处方，测试其对乳糜泻相关过敏反应的免疫耐受治疗作用。方法 本研究利用沉淀自组装法制备聚合物脂质杂化纳米粒（PLNs），载药后超滤离心法得到浓缩纳米药物水溶液；透射电镜观察其形态；激光粒度分析仪考察粒径、Zeta电位和稳定性；BCA蛋白定量测试及分光光度计考察包封率； 透析袋法考察其体外释药特性；迟发超敏反应考察其免疫抑制效应。结果 制备的 PLNGliadin、PLNRapa及PLNGliadin+Rapa纳米粒形态规整，分布良好，粒径分别为（198.04±10.98）nm、（70.73±6.51）nm、（200.98±0.77）nm；Zeta电位分别为（-29.71±5.67）mV、（-41.55±1.13）mV、（-44.80±4.93）mV；PLNGliadin及PLNGliadin+Rapa的Gliadin包封率分别为（43.05±3.35）%与（41.79±4.93）%；PLNRapa及PLNGliadin+Rapa的Rapa包封率分别为（38.05±6.26）%和（26.13±1.30）% 。三种PLNs纳米药物缓释特性明显；药效学试验结果表明三种PLNs纳米药物均能降低由Gliadin刺激造成的足底肿胀超敏反应，PLNGliadin+Rapa效果最显著，且两次预防治疗比单次预防治疗效果好。结论 搭载Gliadin-Rapa的PLNs递送体系结构稳定，缓释作用突出，能有效抑制乳糜泻相关的过敏反应，是治疗乳糜泻的潜在方法。
中文关键词: 麦醇溶蛋白 聚乳酸-羟基乙酸共聚物 缓释 雷帕霉素 乳糜泻 二硬脂酰基磷脂酰乙醇胺-聚乙二醇 聚合物脂质杂化纳米粒
Abstract:ObjectiveThe compound polymeric lipid hybrid nanoparticles (PLNs) loaded with gliadin-rapamycin (Rapa) were designed and prepared, and their immune tolerance effect on celiac disease related allergic reactions was tested by optimizing the prescription of structural characterization, stability, and sustained-release characteristics. Methods In this study, the composite PLN were prepared by precipitation self-assembly method, and the aqueous solution of nanoparticles was concentrated by ultrafiltration centrifugation after drug loading. The morphology was observed by transmission electron microscopy. Particle size, Zeta potential, and stability were investigated by laser particle size analyzer. The encapsulation rate was measured by BCA protein quantification Kit and spectrophotometer. In vitro release properties were investigated by dialysis bag. The immunosuppressive effect was investigated by delayed hypersensitivity. Results The prepared PLNGliadin, PLNRapa and PLNGliadin+Rapa had regular shape and good distribution, with particle sizes of (198.04±10.98) nm, (70.73±6.51) nm and (200.98±0.77) nm, respectively. Zeta potentials of PLNGliadin, PLNRapa and PLNGliadin+Rapa were (-29.71±5.67) mV, (-41.55±1.13) mV, (-44.8±4.93) mV, respectively. The gliadin encapsulation rates of PLNGliadin and PLNGliadin+Rapa were (43.05±3.35)% and (41.79±4.93)%, respectively. The rapamycin encapsulation rates of PLNRapa and PLNGliadin+Rapa were (38.05±6.26)% and (26.13±1.30)%, respectively. The sustained release characteristics of the three PLNs nano-drugs were obvious. Pharmacodynamic test results showed that all three PLNs nanodrugs could reduce plantar swelling hypersensitivity caused by gliadin stimulation, and PLNGliadin+Rapa had the most significant effect. At the same time, twice prophylactic treatments were better than once prophylactic treatment. Conclusion The composite nanoparticles-based drug delibery system loaded with gliadin-rapamycin has a stable structure and outstanding slow-release effect, which can effectively inhibit the allergic reactions related to Celiac disease and is a potential method for the treatment of celiac disease.
keywords: Gliadin Poly (lactic-co-glycolic acid) Slow release Rapamycin Celiac disease DSPE-PEG Polymeric lipid hybrid nanoparticle
文章编号： 中图分类号： 文献标志码：A
基金项目:国家自然科学基金（82000621）
引用文本：
范文涛，陶雨文，范志宁，赵黎黎.麦醇溶蛋白-雷帕霉素复合纳米颗粒治疗乳糜泻的探索研究[J].中国临床研究,2022,35(5):593-598,605.
范文涛，陶雨文，范志宁，赵黎黎.麦醇溶蛋白-雷帕霉素复合纳米颗粒治疗乳糜泻的探索研究[J].中国临床研究,2022,35(5):593-598,605.