Novel rivaroxaban—loaded poly(lactic-co-glycolic acid)/poloxamer nanoparticles: preparation, physicochemical characterization, in vitro evaluation of time-dependent anticoagulant activity and toxicological profile. (8th January 2021)

• Record Type: Journal Article
• Authors: Machado, Monique Etnea; de Souza Furtado, Priscila; da Costa Bernardes Araújo, Cristina; Simon, Alice; de Moraes, Marcela Cristina; Rodrigues Pereira da Silva, Luiz Cláudio; do Carmo, Flávia Almada; Cabral, Lucio Mendes; Sathler, Plínio Cunha
• Is Part Of: Nanotechnology. Volume 32:Number 13(2021)
• Publication Date: 2021-01-08
• Subjects: hemostasis -- thrombosis -- rivaroxaban -- pharmaceutical nanotechnology -- polymeric nanoparticles; Nanotechnology -- Periodicals; Nanotechnology -- Periodicals; Nanotechnology; Publications périodiques; Nanotechnologies; Periodicals; 620.5
• DOI: 10.1088/1361-6528/abd0b5
• Languages: English
• ISSNs: 0957-4484

Abstract

Abstract: 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.