Supramolecular self-assembly of amantadine hydrochloride with ferulic acidviadual optimization strategy establishes a precedent of synergistic antiviral drug-phenolic acid nutraceutical cocrystal
| Autor: | Cui-Wei Yan, Ling-Yang Wang, Yue-Ming Yu, Yuan-Yuan Niu, Zhi-Yong Wu, Yan-Tuan Li, Ming-Yu Zhao |
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| Rok vydání: | 2021 |
| Předmět: |
endocrine system
010405 organic chemistry medicine.drug_class Hydrogen bond Amantadine Hydrochloride Phenolic acid 010402 general chemistry 01 natural sciences Biochemistry Combinatorial chemistry Cocrystal 0104 chemical sciences Analytical Chemistry Ferulic acid chemistry.chemical_compound Nutraceutical chemistry In vivo Electrochemistry medicine Environmental Chemistry Antiviral drug Spectroscopy |
| Zdroj: | The Analyst. 146:3988-3999 |
| ISSN: | 1364-5528 0003-2654 |
| Popis: | To display the capability of the phenolic acid nutraceutical ferulic acid (FLA) in optimizing the in vitro/in vivo properties of the antiviral drug amantadine hydrochloride (AMH) and achieve synergistically enhanced antiviral effects, thereby gaining some new insights into pharmaceutical cocrystals of antiviral drugs with phenolic acid nutraceuticals, a cocrystallization strategy of dual optimization was created. Based on this strategy, the first drug-phenolic acid nutraceutical cocrystal of AMH with FLA, namely AMH-FLA-H2O, was successfully assembled and completely characterized by employing single-crystal X-ray diffraction and other analytical techniques. The cocrystal was revealed to be composed of AMH, FLA, and water molecules in the ratio of 3 : 1 : 1.5, and charge-assisted hydrogen bonds containing chloride ions crucially maintained the crystal lattice together with water molecules. The in vitro/in vivo properties of the cocrystal were systematically evaluated via both theoretical and experimental methods, and the results indicate that the dissolubility of AMH is down-regulated by two-thirds in the cocrystal, resulting in its potential for sustained pharmacokinetic release and the elimination of the adverse effects of AMH. More importantly, the enhanced antiviral effects of the current cocrystal were proven against four viral strains, and the pharmaceutical synergy between AMH and FLA was realized with a combination index (CI) of less than 1. Thus, the present work provides a novel crystalline product with bright commercial prospect for the classical antiviral drug AMH and also establishes an avenue for the synergetic antiviral application of nutraceutical phenolic acids via the cocrystallization strategy of dual optimization. |
| Databáze: | OpenAIRE |
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