氩特异性丝氨酸蛋白酶靶向一水托沙班-聚(乳酸-共聚乙醇酸)纳米颗粒:通过体内外荧光可视化研究Stuart-Prower因子的靶向性和肠道分布。

IF 4.4 2区 医学 Q1 PHARMACOLOGY & PHARMACY
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引用次数: 0

摘要

本研究的目的是配制聚(乳酸-共聚乙酸)(PLGA)载体并考察其潜力,以促进一水托沙坦酯(ETM)的靶向给药。利用纳米沉淀技术有效地配制了 ETM-PLGA-NPs 。对 ETM-PLGA-NPs 的粒度、药物包载率、ZETA电位、肠道吸收评估、傅立叶变换红外光谱、扫描电镜、药物溶出行为和组织病理学研究进行了描述。制得的 NPs 外形大致呈球形,粒径为 99.85 d.nm,PDI 为 0.478,zeta 电位为 38.5 mV,最大药物包载率为 82.1%。傅立叶变换红外光谱测量结果表明,药物在预制成纳米颗粒后化学稳定性保持不变。体外药物释放行为遵循樋口模型,结果表明,优化后的纳米粒子的早期猝灭释放率为 30%,持续释放率为 78%,释放时间长达 120 小时。体外数据显示,ETM 与 PLGA 的比例为 1:10,ETM 释放更持久,封装效率更高。用倒置荧光显微镜拍摄的图像显示,NPs 既能大大增加肠道中 ETM 的积累量,又能使 ETM 更容易进入肠道细胞膜下。研究发现,使用 PLGA 纳米粒子包裹 ETM 可延长循环时间(aPTT、PT、TT)。体内研究发现,封装的纳米颗粒对血液学参数、肺、肝或肾组织没有负面影响。综上所述,纳米粒子是一种潜在的给药方法,可增加 ETM 的口服吸收和抗血栓活性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Arg-Specific serine Protease-Targeted edoxaban tosylate monohydrate-Poly (lactic-co-glycolic acid) Nanoparticles: Investigating Stuart-Prower factor targeting and intestinal distribution through Ex-Vivo fluorescent visualization

Arg-Specific serine Protease-Targeted edoxaban tosylate monohydrate-Poly (lactic-co-glycolic acid) Nanoparticles: Investigating Stuart-Prower factor targeting and intestinal distribution through Ex-Vivo fluorescent visualization

The goal of the current study was to formulate and examine the potential of poly (lactic-co-glycolic acid) (PLGA) as carriers to facilitate the targeted administration of edoxaban tosylate monohydrate (ETM). ETM-PLGA-NPs were effectively formulated using the nanoprecipitation technique. Particle size, drug entrapment percentage, zeta potential, assessment of intestinal absorption, FT-IR, SEM, drug dissolution behavior, and histopathology investigations were used to describe ETM-PLGA-NPs. The produced NPs had a roughly spherical shape with a particle size of 99.85 d.nm, a PDI of 0.478, and a zeta potential of 38.5 mV with a maximum drug entrapment of 82.1 %. FTIR measurements showed that the drug’s chemical stability remained intact after preapred into nanoparticles. In vitro drug release behavior followed the Higuchi model and revealed an early burst release of 30 % and persistent drug release of 78 % from optimized NPs for up to 120 hrs. According to in vitro data, a 1:10 ratio of ETM to PLGA provided longer-lasting ETM release and improved encapsulation efficiency. Images captured with an inverted fluorescent microscope exhibited that NPs may both greatly increase the amount of ETM accumulated in the intestinal tract and make it easier for ETM to enter the membrane beneath the cells of the intestines. The study found that using PLGA nanoparticles to encapsulate the ETM resulted in longer circulation duration (aPTT, PT, TT). In vivo investigations found that nanoparticles encapsulated had no negative impact on hematological parameters, lung, liver, or kidney tissues. All things considered, the NPs are a potential delivery method to increase the oral absorption and antithrombotic activity of ETM.

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来源期刊
CiteScore
8.80
自引率
4.10%
发文量
211
审稿时长
36 days
期刊介绍: The European Journal of Pharmaceutics and Biopharmaceutics provides a medium for the publication of novel, innovative and hypothesis-driven research from the areas of Pharmaceutics and Biopharmaceutics. Topics covered include for example: Design and development of drug delivery systems for pharmaceuticals and biopharmaceuticals (small molecules, proteins, nucleic acids) Aspects of manufacturing process design Biomedical aspects of drug product design Strategies and formulations for controlled drug transport across biological barriers Physicochemical aspects of drug product development Novel excipients for drug product design Drug delivery and controlled release systems for systemic and local applications Nanomaterials for therapeutic and diagnostic purposes Advanced therapy medicinal products Medical devices supporting a distinct pharmacological effect.
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