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

作者 ： Monique Etnea Machado ¹ , Priscila de Souza Furtado ¹ , Cristina da Costa Bernardes Araújo ^1,2 , Alice Simon ² , Marcela Cristina de Moraes ³ , Luiz Cláudio Rodrigues Pereira da Silva ² , Flávia Almada do Carmo ² , Lucio Mendes Cabral ²  and Plínio Cunha Sathler ¹

¹  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

²  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

³  Fluminense Federal University, Department of Organic Chemistry, Outeiro de São João Batista s/n, Niterói, RJ, CEP 24210-240, Brazil

摘要： 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.

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