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  • Sodium montmorillonite/amine-containing drugs complexes: new insights on intercalated drugs arrangement into layered carrier material.

Sodium montmorillonite/amine-containing drugs complexes: new insights on intercalated drugs arrangement into layered carrier material.

PloS one (2015-03-25)
Murilo L Bello, Aridio M Junior, Bárbara A Vieira, Luiza R S Dias, Valéria P de Sousa, Helena C Castro, Carlos R Rodrigues, Lucio M Cabral
초록

Layered drug delivery carriers are current targets of nanotechnology studies since they are able to accommodate pharmacologically active substances and are effective at modulating drug release. Sodium montmorillonite (Na-MMT) is a clay that has suitable properties for developing new pharmaceutical materials due to its high degree of surface area and high capacity for cation exchange. Therefore Na-MMT is a versatile material for the preparation of new drug delivery systems, especially for slow release of protonable drugs. Herein, we describe the intercalation of several amine-containing drugs with Na-MMT so we can derive a better understanding of how these drugs molecules interact with and distribute throughout the Na-MMT interlayer space. Therefore, for this purpose nine sodium montmorillonite/amine-containing drugs complexes (Na-MMT/drug) were prepared and characterized. In addition, the physicochemical properties of the drugs molecules in combination with different experimental conditions were assessed to determine how these factors influenced experimental outcomes (e.g. increase of the interlayer spacing versus drugs arrangement and orientation). We also performed a molecular modeling study of these amine-containing drugs associated with different Na-MMT/drug complex models to analyze the orientation and arrangement of the drugs molecules in the complexes studied. Six amine-containing drugs (rivastigmine, doxazosin, 5-fluorouracil, chlorhexidine, dapsone, nystatin) were found to successfully intercalate Na-MMT. These findings provide important insights on the interlayer aspect of the molecular systems formed and may contribute to produce more efficient drug delivery nanosystems.

MATERIALS
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Sigma-Aldrich
2-Phenyl-5-benzimidazolesulfonic acid, 96%
Sigma-Aldrich
Chlorhexidine, ≥99.5%
Sigma-Aldrich
5-Fluorouracil, ≥99% (HPLC), powder
Sigma-Aldrich
Fluorouracil, meets USP testing specifications
Sigma-Aldrich
4-Aminobenzoic acid, ReagentPlus®, 99%
Sigma-Aldrich
4-Aminophenyl sulfone, 97%
Sigma-Aldrich
4-Aminobenzoic acid, ReagentPlus®, ≥99%
Sigma-Aldrich
4-Aminobenzoic acid, purified by sublimation, ≥99%