Adsorption and intercalation of benznidazole and nifurtimox in montmorillonite: An experimental-theoretical study


Por: Pérez de la Luz A., Jiménez-Mondragón A., Soriano-Santiago M., Alva-Ensastegui J.C., Soto-Estrada A.M., Ortiz-Quiñonez J.L., Campos-Fernández L., Barrientos-Salcedo C., Lara-Corona V.H., Herrera-Valencia E.E., Soriano-Correa C., Sainz-Díaz C.I.

Publicada: 1 ene 2026
Resumen:
© 2026 The Authors.American trypanosomiasis or Chagas disease, caused by Trypanosoma cruzi , remains a therapeutic challenge worldwide. Benznidazole (BNZ) and Nifurtimox (NFX) are drugs used for its treatment; however, they are not efficacy in the chronic phase of the disease, which leads to high toxicity due to prolonged use. This research addresses the use of nanomaterials (Nano clay and VHS) as natural systems capable of adsorbing drugs with low water solubility, allowing improved release to reduce adverse effects. The objectives were to study the crystal structures of NFX and BNZ at the atomic scale, using quantum mechanics calculations and experimental techniques (XRD, FTIR, TGA, SEM-EDS), to understand their physicochemical characteristics in the crystalline state, as well as to explore their hydration by molecular dynamics simulations. The intercalation of these drugs in the confined space between the montmorillonite layers was evaluated by DFT calculations to propose novel clay-drug nanocomplexes for enhancing the solubility and bioavailability. The results showed that NFX intercalation in both clays presented a loss of crystallinity, with a displacement of the (001) plane, while BNZ exhibited slight intercalation being adsorbed mainly on the external surfaces of clay mineral solids. Montmorillonite enhanced the stability of these drugs through interactions (hydrogen bonding, electrostatic interactions, and coordination with Na+ cations), adopting parallel orientations with the clay layers. The intercalation of NFX and BNZ into the interlaminar space of montmorillonite was energetically favorable. The design of clay-drug nanocomplexes could be a potential alternative for developing new, more effective and safer therapeutic schemes against Chagas disease.

Filiaciones:
Pérez de la Luz A.:
 Departamento de Química, Universidad Autónoma Metropolitana-Iztapalapa, Av. San Rafael Atlixco 186, Col. Vicentina, Ciudad de México 09340, Mexico

 Área de Química Computacional, Facultad de Estudios Superiores Zaragoza (FES Zaragoza), Carrera de QFB, Universidad Nacional Autónoma de México (UNAM), Iztapalapa, C.P., 09230 Ciudad de México, Mexico

 Instituto Andaluz de Ciencias de la Tierra, Consejo Superior de Investigaciones Científicas, IACT-CSIC, Av. de las Palmeras, 4, 18100-Armilla, Granada, Spain

Jiménez-Mondragón A.:
 Departamento de Química, Universidad Autónoma Metropolitana-Iztapalapa, Av. San Rafael Atlixco 186, Col. Vicentina, Ciudad de México 09340, Mexico

Soriano-Santiago M.:
 Departamento de Química, Universidad Autónoma Metropolitana-Iztapalapa, Av. San Rafael Atlixco 186, Col. Vicentina, Ciudad de México 09340, Mexico

Alva-Ensastegui J.C.:
 Universidad Autónoma del Estado de México, Facultad de Química, C.P. 50180, Toluca, Estado de México, Mexico

Soto-Estrada A.M.:
 Departamento de Química, Universidad Autónoma Metropolitana-Iztapalapa, Av. San Rafael Atlixco 186, Col. Vicentina, Ciudad de México 09340, Mexico

Ortiz-Quiñonez J.L.:
 Departamento de Química, Universidad Autónoma Metropolitana-Iztapalapa, Av. San Rafael Atlixco 186, Col. Vicentina, Ciudad de México 09340, Mexico

Campos-Fernández L.:
 Carrera de Ingeniería Química, FES-Zaragoza UNAM, Iztapalapa, C.P. 09230, Ciudad de México, Mexico

Barrientos-Salcedo C.:
 Laboratorio de Química Médica y Quimiogenómica, Universidad Veracruzana, C.P. 91700, Veracruz, Mexico

Lara-Corona V.H.:
 Departamento de Química, Universidad Autónoma Metropolitana-Iztapalapa, Av. San Rafael Atlixco 186, Col. Vicentina, Ciudad de México 09340, Mexico

Herrera-Valencia E.E.:
 Unidad de Bioingeniería, Carrera de Ingeniería Química, FES-Zaragoza, UNAM, Iztapalapa, C.P. 09230, Ciudad de México, Mexico

Soriano-Correa C.:
 Área de Química Computacional, Facultad de Estudios Superiores Zaragoza (FES Zaragoza), Carrera de QFB, Universidad Nacional Autónoma de México (UNAM), Iztapalapa, C.P., 09230 Ciudad de México, Mexico

 Instituto Andaluz de Ciencias de la Tierra, Consejo Superior de Investigaciones Científicas, IACT-CSIC, Av. de las Palmeras, 4, 18100-Armilla, Granada, Spain

Sainz-Díaz C.I.:
 Instituto Andaluz de Ciencias de la Tierra, Consejo Superior de Investigaciones Científicas, IACT-CSIC, Av. de las Palmeras, 4, 18100-Armilla, Granada, Spain
ISSN: 01691317
Editorial
Elsevier Ltd, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS, Países Bajos
Tipo de documento: Article
Volumen: 284 Número:
Páginas:
WOS Id: 001678280100001

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