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

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 prolo...

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Detalles Bibliográficos
Autores: Pérez de la Luz, Alexander, Jiménez-Mondragón, Alfredo, Soriano-Santiago, Miriam, Alva-Ensastegui, J. C., Soto-Estrada, Ana María, Ortiz-Quiñonez, Jose Luis, Campos-Fernandez, Linda Verónica, Barrientos-Salcedo, Carolina, Lara, Víctor Hugo, Herrera-Valencia, Edtson Emilio, Soriano-Correa, Catalina, Sainz-Díaz, C. Ignacio
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2026
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/417506
Acceso en línea:http://hdl.handle.net/10261/417506
https://doi.org/10.1016/j.clay.2026.108142
Access Level:acceso abierto
Palabra clave:Trypanosoma cruzi
Benznidazole
Nifurtimox
Clay-drug nanocomplexes
High toxicity
Molecular modeling
Clay minerals
DFT calculations
Intercalation
Descripción
Sumario: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.