Evidence of Strong Guest–Host Interactions ...
Type de document :
Article dans une revue scientifique: Article original
URL permanente :
Titre :
Evidence of Strong Guest–Host Interactions in Simvastatin Loaded in Mesoporous Silica MCM-41
Auteur(s) :
Cordeiro, Teresa [Auteur]
Matos, Inês [Auteur]
Danède, Florence [Auteur]
Unité Matériaux et Transformations - UMR 8207 [UMET]
Sotomayor, João C. [Auteur]
Fonseca, Isabel M. [Auteur]
Corvo, Marta C. [Auteur]
Dionísio, Madalena [Auteur]
Viciosa, María Teresa [Auteur]
Affouard, Frédéric [Auteur]
Unité Matériaux et Transformations (UMET) - UMR 8207
Correia, Natália T. [Auteur]
Unité Matériaux et Transformations - UMR 8207 [UMET]
Matos, Inês [Auteur]
Danède, Florence [Auteur]
Unité Matériaux et Transformations - UMR 8207 [UMET]
Sotomayor, João C. [Auteur]
Fonseca, Isabel M. [Auteur]
Corvo, Marta C. [Auteur]
Dionísio, Madalena [Auteur]
Viciosa, María Teresa [Auteur]
Affouard, Frédéric [Auteur]
Unité Matériaux et Transformations (UMET) - UMR 8207
Correia, Natália T. [Auteur]
Unité Matériaux et Transformations - UMR 8207 [UMET]
Titre de la revue :
Pharmaceutics
Nom court de la revue :
Pharmaceutics
Numéro :
15
Pagination :
1320
Éditeur :
MDPI AG
Date de publication :
2023-04-22
ISSN :
1999-4923
Résumé en anglais : [en]
A rational design of drug delivery systems requires in-depth knowledge not only of the drug itself, in terms of physical state and molecular mobility, but also of how it is distributed among a carrier and its interactions ...
Lire la suite >A rational design of drug delivery systems requires in-depth knowledge not only of the drug itself, in terms of physical state and molecular mobility, but also of how it is distributed among a carrier and its interactions with the host matrix. In this context, this work reports the behavior of simvastatin (SIM) loaded in mesoporous silica MCM-41 matrix (average pore diameter ~3.5 nm) accessed by a set of experimental techniques, evidencing that it exists in an amorphous state (X-ray diffraction, ssNMR, ATR-FTIR, and DSC). The most significant fraction of SIM molecules corresponds to a high thermal resistant population, as shown by thermogravimetry, and which interacts strongly with the MCM silanol groups, as revealed by ATR-FTIR analysis. These findings are supported by Molecular Dynamics (MD) simulations predicting that SIM molecules anchor to the inner pore wall through multiple hydrogen bonds. This anchored molecular fraction lacks a calorimetric and dielectric signature corresponding to a dynamically rigid population. Furthermore, differential scanning calorimetry showed a weak glass transition that is shifted to lower temperatures compared to bulk amorphous SIM. This accelerated molecular population is coherent with an in-pore fraction of molecules distinct from bulklike SIM, as highlighted by MD simulations. MCM-41 loading proved to be a suitable strategy for a long-term stabilization (at least three years) of simvastatin in the amorphous form, whose unanchored population releases at a much higher rate compared to the crystalline drug dissolution. Oppositely, the surface-attached molecules are kept entrapped inside pores even after long-term release assays.Lire moins >
Lire la suite >A rational design of drug delivery systems requires in-depth knowledge not only of the drug itself, in terms of physical state and molecular mobility, but also of how it is distributed among a carrier and its interactions with the host matrix. In this context, this work reports the behavior of simvastatin (SIM) loaded in mesoporous silica MCM-41 matrix (average pore diameter ~3.5 nm) accessed by a set of experimental techniques, evidencing that it exists in an amorphous state (X-ray diffraction, ssNMR, ATR-FTIR, and DSC). The most significant fraction of SIM molecules corresponds to a high thermal resistant population, as shown by thermogravimetry, and which interacts strongly with the MCM silanol groups, as revealed by ATR-FTIR analysis. These findings are supported by Molecular Dynamics (MD) simulations predicting that SIM molecules anchor to the inner pore wall through multiple hydrogen bonds. This anchored molecular fraction lacks a calorimetric and dielectric signature corresponding to a dynamically rigid population. Furthermore, differential scanning calorimetry showed a weak glass transition that is shifted to lower temperatures compared to bulk amorphous SIM. This accelerated molecular population is coherent with an in-pore fraction of molecules distinct from bulklike SIM, as highlighted by MD simulations. MCM-41 loading proved to be a suitable strategy for a long-term stabilization (at least three years) of simvastatin in the amorphous form, whose unanchored population releases at a much higher rate compared to the crystalline drug dissolution. Oppositely, the surface-attached molecules are kept entrapped inside pores even after long-term release assays.Lire moins >
Langue :
Anglais
Comité de lecture :
Oui
Audience :
Internationale
Vulgarisation :
Non
Établissement(s) :
Université de Lille
CNRS
INRAE
ENSCL
CNRS
INRAE
ENSCL
Collections :
Équipe(s) de recherche :
Matériaux Moléculaires et Thérapeutiques
Date de dépôt :
2023-12-11T13:29:20Z