Different Drug Mobilities in Hydrophobic Cavities of Host-Guest Complexes between ß-Cyclodextrin and 5-Fluorouracil at Different Stoichiometries: A Molecular Dynamics Study in Water.
Int J Mol Sci
; 25(11)2024 May 28.
Article
em En
| MEDLINE
| ID: mdl-38892075
ABSTRACT
Cyclodextrins (CDs) are cyclic oligosaccharides able to form noncovalent water-soluble complexes useful in many different applications for the solubilization, delivery, and greater bioavailability of hydrophobic drugs. The complexation of 5-fluorouracil (5-FU) with natural or synthetic cyclodextrins permits the solubilization of this poorly soluble anticancer drug. In this theoretical work, the complexes between ß-CD and 5-FU are investigated using molecular mechanics (MM) and molecular dynamics (MD) simulations in water. The inclusion complexes are formed thanks to the favorable intermolecular interactions between ß-CD and 5-FU. Both 11 and 12 ß-CD/5-FU stoichiometries are investigated, providing insight into their interaction geometries and stability over time in water. In the 12 ß-CD/5-FU complexes, the intermolecular interactions affect the drug's mobility, suggesting a two-step release mechanism a fast release for the more exposed and hydrated drug molecule, with greater freedom of movement near the ß-CD rims, and a slow one for the less-hydrated and well-encapsulated and confined drug. MD simulations study the intermolecular interactions between drugs and specific carriers at the atomistic level, suggesting a possible release mechanism and highlighting the role of the impact of the drug concentration on the kinetics process in water. A comparison with experimental data in the literature provides further insights.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Água
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Beta-Ciclodextrinas
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Simulação de Dinâmica Molecular
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Interações Hidrofóbicas e Hidrofílicas
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Fluoruracila
Idioma:
En
Revista:
Int J Mol Sci
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Itália