Department of Pharmaceutics, Crescent School of Pharmacy, B.S.Abdur Rahman Crescent Institute of Science & Technology, Chennai, Tamilnadu 600048, India.
Department of Pharmaceutics, Crescent School of Pharmacy, B.S.Abdur Rahman Crescent Institute of Science & Technology, Chennai, Tamilnadu 600048, India.
Eur J Pharm Biopharm. 2024 Oct;203:114459. doi: 10.1016/j.ejpb.2024.114459. Epub 2024 Aug 20.
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.
本研究的目的是制备并考察聚(乳酸-共-乙醇酸)(PLGA)作为载体促进硫酸依度沙班一水合物(ETM)靶向给药的潜力。采用纳米沉淀技术有效地制备了 ETM-PLGA-NPs。通过粒径、药物包封率、Zeta 电位、肠吸收评估、傅里叶变换红外光谱(FT-IR)、扫描电子显微镜(SEM)、药物溶出行为和组织病理学研究来描述 ETM-PLGA-NPs。所制备的 NPs 呈大致球形,粒径为 99.85 d.nm,PDI 为 0.478,Zeta 电位为 38.5 mV,最大药物包封率为 82.1%。FTIR 测量表明,药物在制备成纳米粒子后其化学稳定性保持完整。体外药物释放行为符合 Higuchi 模型,显示优化的 NPs 在 120 小时内早期释放 30%,持续释放 78%的药物。根据体外数据,ETM 与 PLGA 的比例为 1:10 可提供更长时间的 ETM 释放并提高包封效率。倒置荧光显微镜拍摄的图像表明,NPs 可能会大大增加 ETM 在肠道中的积累量,并使 ETM 更容易进入肠道细胞下方的膜。研究发现,使用 PLGA 纳米粒子包封 ETM 可延长 aPTT、PT、TT 的循环时间。体内研究发现,包封的纳米粒子对血液学参数、肺、肝、肾组织没有负面影响。综上所述,NPs 是一种潜在的给药方法,可以提高 ETM 的口服吸收和抗血栓活性。