Federal University of Rio de Janeiro, Department of Clinical and Toxicological Analysis, Faculty of Pharmacy, Av. Carlos Chagas Filho, 373, CCS, Bloco A Subsolo, sl24, Rio de Janeiro, RJ, CEP 21941-902, Brazil.
Federal University of Rio de Janeiro, Department of Drugs and Pharmaceutics, Faculty of Pharmacy, Av. Carlos Chagas Filho, 373, CCS, Bloco L Subsolo, sl20, Rio de Janeiro, RJ, CEP 21941-902, Brazil.
Nanotechnology. 2021 Mar 26;32(13):135101. doi: 10.1088/1361-6528/abd0b5.
Rivaroxaban (RXB), an oral direct factor Xa inhibitor, presents innovative therapeutic profile. However, RXB has shown adverse effects, mainly due to pharmacokinetic limitations, highlighting the importance of developing more effective formulations. Therefore, this work aims at the preparation, physicochemical characterization and in vitro evaluation of time-dependent anticoagulant activity and toxicology profile of RXB-loaded poly(lactic-co-glycolic acid) (PLGA)/poloxamer nanoparticles (RXBNps). RXBNp were produced by nanoprecipitation method and physicochemical characteristics were evaluated. In vitro analysis of time-dependent anticoagulant activity was performed by prothrombin time test and toxicological profile was assessed by hemolysis and MTT reduction assays. The developed RXBNp present spherical morphology with average diameter of 205.5 ± 16.95 nm (PdI 0.096 ± 0.04), negative zeta potential (-26.28 ± 0.77 mV), entrapment efficiency of 91.35 ± 2.40%, yield of 41.81 ± 1.68% and 3.72 ± 0.07% of drug loading. Drug release was characterized by an initial fast release followed by a sustained release with 28.34 ± 2.82% of RXB available in 72 h. RXBNp showed an expressive time-dependent anticoagulant activity in human and rat blood plasma and non-toxic profile. Based on the results presented, it is possible to consider that RXBNp may be able to assist in the development of promising new therapies for treatment of thrombotic disorders.
利伐沙班（RXB）是一种口服直接 Xa 因子抑制剂，具有创新的治疗特性。然而，RXB 已显示出不良反应，主要是由于药代动力学限制，这凸显了开发更有效制剂的重要性。因此，本工作旨在制备、理化特性表征以及体外评估载利伐沙班的聚（乳酸-共-乙醇酸）（PLGA）/泊洛沙姆纳米粒（RXBNps）的时变抗凝活性和毒理学特征。通过纳米沉淀法制备了 RXBNp，并对其理化特性进行了评价。通过凝血酶原时间试验进行体外时变抗凝活性分析，通过溶血和 MTT 降低试验评估毒理学特征。所开发的 RXBNp 呈现出球形形态，平均直径为 205.5±16.95nm（PdI 0.096±0.04），负 ζ 电位（-26.28±0.77mV），包封效率为 91.35±2.40%，产率为 41.81±1.68%，载药量为 3.72±0.07%。药物释放表现为初始快速释放，随后持续释放，72 小时内有 28.34±2.82%的 RXB 可用。RXBNp 在人及大鼠血浆中表现出明显的时变抗凝活性和非毒性特征。基于所呈现的结果，可以认为 RXBNp 可能有助于开发治疗血栓性疾病的有前途的新疗法。
