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Nanostructured lipid carriers containing benznidazole: physicochemical, biopharmaceutical and cellular in vitro studies

Chagas disease is a neglected endemic disease prevalent in Latin American countries, affecting around 8 million people. The first-line treatment, benznidazole (BNZ), is effective in the acute stage of the disease but has limited efficacy in the chronic stage, possibly because current treatment regim...

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Autores principales: Muraca, Giuliana, Ruiz, María Esperanza, Gambaro, Rocío C, Scioli-Montoto, Sebastián, Sbaraglini, María Laura, Padula, Gisel, Cisneros, José Sebastián, Chain, Cecilia Yamil, Álvarez, Vera A, Huck-Iriart, Cristián, Castro, Guillermo R, Piñero, María Belén, Marchetto, Matias Ildebrando, Alba Soto, Catalina, Islan, Germán A, Talevi, Alan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Beilstein-Institut 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10390827/
https://www.ncbi.nlm.nih.gov/pubmed/37533841
http://dx.doi.org/10.3762/bjnano.14.66
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author Muraca, Giuliana
Ruiz, María Esperanza
Gambaro, Rocío C
Scioli-Montoto, Sebastián
Sbaraglini, María Laura
Padula, Gisel
Cisneros, José Sebastián
Chain, Cecilia Yamil
Álvarez, Vera A
Huck-Iriart, Cristián
Castro, Guillermo R
Piñero, María Belén
Marchetto, Matias Ildebrando
Alba Soto, Catalina
Islan, Germán A
Talevi, Alan
author_facet Muraca, Giuliana
Ruiz, María Esperanza
Gambaro, Rocío C
Scioli-Montoto, Sebastián
Sbaraglini, María Laura
Padula, Gisel
Cisneros, José Sebastián
Chain, Cecilia Yamil
Álvarez, Vera A
Huck-Iriart, Cristián
Castro, Guillermo R
Piñero, María Belén
Marchetto, Matias Ildebrando
Alba Soto, Catalina
Islan, Germán A
Talevi, Alan
author_sort Muraca, Giuliana
collection PubMed
description Chagas disease is a neglected endemic disease prevalent in Latin American countries, affecting around 8 million people. The first-line treatment, benznidazole (BNZ), is effective in the acute stage of the disease but has limited efficacy in the chronic stage, possibly because current treatment regimens do not eradicate transiently dormant Trypanosoma cruzi amastigotes. Nanostructured lipid carriers (NLC) appear to be a promising approach for delivering pharmaceutical active ingredients as they can have a positive impact on bioavailability by modifying the absorption, distribution, and elimination of the drug. In this study, BNZ was successfully loaded into nanocarriers composed of myristyl myristate/Crodamol oil/poloxamer 188 prepared by ultrasonication. A stable NLC formulation was obtained, with ≈80% encapsulation efficiency (%EE) and a biphasic drug release profile with an initial burst release followed by a prolonged phase. The hydrodynamic average diameter and zeta potential of NLC obtained by dynamic light scattering were approximately 150 nm and −13 mV, respectively, while spherical and well-distributed nanoparticles were observed by transmission electron microscopy. Fourier-transform infrared spectroscopy, differential scanning calorimetry, thermogravimetric analysis, and small-angle X-ray scattering analyses of the nanoparticles indicated that BNZ might be dispersed in the nanoparticle matrix in an amorphous state. The mean size, zeta potential, polydispersity index, and %EE of the formulation remained stable for at least six months. The hemolytic effect of the nanoparticles was insignificant compared to that of the positive lysis control. The nanoparticle formulation exhibited similar performance in vitro against T. cruzi compared to free BNZ. No formulation-related cytotoxic effects were observed on either Vero or CHO cells. Moreover, BNZ showed a 50% reduction in CHO cell viability at 125 µg/mL, whereas NLC-BNZ and non-loaded NLC did not exert a significant effect on cell viability at the same concentration. These results show potential for the development of new nanomedicines against T. cruzi.
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spelling pubmed-103908272023-08-02 Nanostructured lipid carriers containing benznidazole: physicochemical, biopharmaceutical and cellular in vitro studies Muraca, Giuliana Ruiz, María Esperanza Gambaro, Rocío C Scioli-Montoto, Sebastián Sbaraglini, María Laura Padula, Gisel Cisneros, José Sebastián Chain, Cecilia Yamil Álvarez, Vera A Huck-Iriart, Cristián Castro, Guillermo R Piñero, María Belén Marchetto, Matias Ildebrando Alba Soto, Catalina Islan, Germán A Talevi, Alan Beilstein J Nanotechnol Full Research Paper Chagas disease is a neglected endemic disease prevalent in Latin American countries, affecting around 8 million people. The first-line treatment, benznidazole (BNZ), is effective in the acute stage of the disease but has limited efficacy in the chronic stage, possibly because current treatment regimens do not eradicate transiently dormant Trypanosoma cruzi amastigotes. Nanostructured lipid carriers (NLC) appear to be a promising approach for delivering pharmaceutical active ingredients as they can have a positive impact on bioavailability by modifying the absorption, distribution, and elimination of the drug. In this study, BNZ was successfully loaded into nanocarriers composed of myristyl myristate/Crodamol oil/poloxamer 188 prepared by ultrasonication. A stable NLC formulation was obtained, with ≈80% encapsulation efficiency (%EE) and a biphasic drug release profile with an initial burst release followed by a prolonged phase. The hydrodynamic average diameter and zeta potential of NLC obtained by dynamic light scattering were approximately 150 nm and −13 mV, respectively, while spherical and well-distributed nanoparticles were observed by transmission electron microscopy. Fourier-transform infrared spectroscopy, differential scanning calorimetry, thermogravimetric analysis, and small-angle X-ray scattering analyses of the nanoparticles indicated that BNZ might be dispersed in the nanoparticle matrix in an amorphous state. The mean size, zeta potential, polydispersity index, and %EE of the formulation remained stable for at least six months. The hemolytic effect of the nanoparticles was insignificant compared to that of the positive lysis control. The nanoparticle formulation exhibited similar performance in vitro against T. cruzi compared to free BNZ. No formulation-related cytotoxic effects were observed on either Vero or CHO cells. Moreover, BNZ showed a 50% reduction in CHO cell viability at 125 µg/mL, whereas NLC-BNZ and non-loaded NLC did not exert a significant effect on cell viability at the same concentration. These results show potential for the development of new nanomedicines against T. cruzi. Beilstein-Institut 2023-07-28 /pmc/articles/PMC10390827/ /pubmed/37533841 http://dx.doi.org/10.3762/bjnano.14.66 Text en Copyright © 2023, Muraca et al. https://creativecommons.org/licenses/by/4.0/This is an open access article licensed under the terms of the Beilstein-Institut Open Access License Agreement (https://www.beilstein-journals.org/bjnano/terms/terms), which is identical to the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0 (https://creativecommons.org/licenses/by/4.0/) ). The reuse of material under this license requires that the author(s), source and license are credited. Third-party material in this article could be subject to other licenses (typically indicated in the credit line), and in this case, users are required to obtain permission from the license holder to reuse the material.
spellingShingle Full Research Paper
Muraca, Giuliana
Ruiz, María Esperanza
Gambaro, Rocío C
Scioli-Montoto, Sebastián
Sbaraglini, María Laura
Padula, Gisel
Cisneros, José Sebastián
Chain, Cecilia Yamil
Álvarez, Vera A
Huck-Iriart, Cristián
Castro, Guillermo R
Piñero, María Belén
Marchetto, Matias Ildebrando
Alba Soto, Catalina
Islan, Germán A
Talevi, Alan
Nanostructured lipid carriers containing benznidazole: physicochemical, biopharmaceutical and cellular in vitro studies
title Nanostructured lipid carriers containing benznidazole: physicochemical, biopharmaceutical and cellular in vitro studies
title_full Nanostructured lipid carriers containing benznidazole: physicochemical, biopharmaceutical and cellular in vitro studies
title_fullStr Nanostructured lipid carriers containing benznidazole: physicochemical, biopharmaceutical and cellular in vitro studies
title_full_unstemmed Nanostructured lipid carriers containing benznidazole: physicochemical, biopharmaceutical and cellular in vitro studies
title_short Nanostructured lipid carriers containing benznidazole: physicochemical, biopharmaceutical and cellular in vitro studies
title_sort nanostructured lipid carriers containing benznidazole: physicochemical, biopharmaceutical and cellular in vitro studies
topic Full Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10390827/
https://www.ncbi.nlm.nih.gov/pubmed/37533841
http://dx.doi.org/10.3762/bjnano.14.66
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