Novel rivaroxaban—loaded poly(lactic-co-glycolic acid)/poloxamer nanoparticles: preparation, physicochemical characterization, in vitro evaluation of time-dependent anticoagulant activity and toxicological profile
- 4 December 2020
- journal article
- research article
- Published by IOP Publishing in Nanotechnology
- Vol. 32 (13), 135101
- https://doi.org/10.1088/1361-6528/abd0b5
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 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 (PT) 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 72h. 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.Keywords
Funding Information
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro
This publication has 78 references indexed in Scilit:
- Cannabinoid derivate-loaded PLGA nanocarriers for oral administration: formulation, characterization, and cytotoxicity studiesInternational Journal of Nanomedicine, 2012
- Poly Lactic-co-Glycolic Acid (PLGA) as Biodegradable Controlled Drug Delivery CarrierPolymers, 2011
- Nanoparticles for drug delivery: The need for precision in reporting particle size parametersEuropean Journal of Pharmaceutics and Biopharmaceutics, 2008
- Etoposide-Loaded PLGA and PCL Nanoparticles I: Preparation and Effect of Formulation VariablesDrug Delivery, 2008
- In-vitro profile and ex-vivo anticoagulant activity of the direct thrombin inhibitor dabigatran and its orally active prodrug, dabigatran etexilateThrombosis and Haemostasis, 2007
- Effects of particle size and surface coating on cellular uptake of polymeric nanoparticles for oral delivery of anticancer drugsBiomaterials, 2005
- In vitro and in vivo studies of the novel antithrombotic agent BAY 59-7939—an oral, direct Factor Xa inhibitorJournal of Thrombosis and Haemostasis, 2005
- In Vitro and In Vivo Evaluation of Oral Heparin–Loaded Polymeric Nanoparticles in RabbitsCirculation, 2002
- Encapsulation of Hydrophilic and Lipophilic Drugs in PLGA Nanoparticles by the Nanoprecipitation MethodDrug Development and Industrial Pharmacy, 1999
- Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assaysJournal of Immunological Methods, 1983