Native Cyclodextrins as Complexation Agents for Pterostilbene: Complex Preparation and Characterization in Solution and in the Solid State
Pterostilbene (3,5-dimethoxy-4′-hydroxystilbene, PTB) is a natural dietary stilbene, occurring primarily in blueberries and Pterocarpus marsupium heartwood. The interest in this compound is related to its different biological and pharmacological properties, such as its antioxidant, anti-inflammatory...
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MDPI AG
2021-12-01
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| Series: | Pharmaceutics |
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| author | Laura Catenacci Alexios I. Vicatos Milena Sorrenti Maria Cristina Bonferoni Mino R. Caira |
| author_facet | Laura Catenacci Alexios I. Vicatos Milena Sorrenti Maria Cristina Bonferoni Mino R. Caira |
| author_sort | Laura Catenacci |
| collection | DOAJ |
| description | Pterostilbene (3,5-dimethoxy-4′-hydroxystilbene, PTB) is a natural dietary stilbene, occurring primarily in blueberries and Pterocarpus marsupium heartwood. The interest in this compound is related to its different biological and pharmacological properties, such as its antioxidant, anti-inflammatory, and anticarcinogenic activities and its capacity to reduce and regulate cholesterol and blood sugar levels. Nevertheless, its use in therapy is hindered by its low aqueous solubility; to overcome this limitation we studied the feasibility of the use of cyclodextrins (CDs) as solubility-enhancing agents. CDs are natural macrocyclic oligomers composed of α-<span style="font-variant: small-caps;">d</span>-glucose units linked by α-1,4 glycosidic bonds to form torus-shaped molecules, responsible for inclusion complex formation with organic molecules. In particular, the aim of this study was to evaluate the feasibility of complexation between PTB and native CDs using various preparative methods. The isolated solid products were characterized using differential scanning calorimetry (DSC), simultaneous thermogravimetric/DSC analysis (TGA/DSC), Fourier transform infrared (FT-IR) spectroscopy, and X-ray diffraction (XRD) on powder and single crystals. The results indicated little or no evidence of the affinity of PTB to complex with α-CD using the kneading method. However, with β-CD and γ-CD thermal analysis revealed an interaction which was also corroborated by FT-IR and <sup>1</sup>H-NMR spectroscopy. With β-CD, a hydrated complex of PTB was isolated and its characterization by single-crystal XRD revealed, for the first time, the mode of inclusion of the PTB molecule in the cavity of a CD. To complement the solid-state data, liquid-phase studies were carried out to establish the effect of CDs on the aqueous solubility of PTB and to determine the complex stoichiometries and the association constants for complex formation. Phase-solubility studies showed A<sub>L</sub>-type profiles for α- and β-CD and a B<sub>S</sub> profile for γ-CD, with K<sub>1:1</sub> values of 1144, 4950, and 133 M<sup>−1</sup> for α-CD·PTB, β-CD·PTB, and γ-CD·PTB, respectively. The stoichiometry of CD·PTB complexes, determined by Job’s method, revealed for each system a 1:1 molar ratio. The dissolution rate of PTB was approximately doubled just by employing simple physical mixtures, but the best performance was achieved by products obtained via kneading and co-precipitation, which effected the complete dissolution of PTB in 40 and 20 min for β-CD and γ-CD, respectively. |
| first_indexed | 2024-03-10T00:44:42Z |
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| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T00:44:42Z |
| publishDate | 2021-12-01 |
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| spelling | doaj.art-fcc6b8ed5c834a79930d38501407b0722023-11-23T15:02:19ZengMDPI AGPharmaceutics1999-49232021-12-01141810.3390/pharmaceutics14010008Native Cyclodextrins as Complexation Agents for Pterostilbene: Complex Preparation and Characterization in Solution and in the Solid StateLaura Catenacci0Alexios I. Vicatos1Milena Sorrenti2Maria Cristina Bonferoni3Mino R. Caira4Department of Drug Sciences, University of Pavia, Viale Taramelli 12, 27100 Pavia, ItalyDepartment of Chemistry, University of Cape Town, Rondebosch 7701, South AfricaDepartment of Drug Sciences, University of Pavia, Viale Taramelli 12, 27100 Pavia, ItalyDepartment of Drug Sciences, University of Pavia, Viale Taramelli 12, 27100 Pavia, ItalyDepartment of Chemistry, University of Cape Town, Rondebosch 7701, South AfricaPterostilbene (3,5-dimethoxy-4′-hydroxystilbene, PTB) is a natural dietary stilbene, occurring primarily in blueberries and Pterocarpus marsupium heartwood. The interest in this compound is related to its different biological and pharmacological properties, such as its antioxidant, anti-inflammatory, and anticarcinogenic activities and its capacity to reduce and regulate cholesterol and blood sugar levels. Nevertheless, its use in therapy is hindered by its low aqueous solubility; to overcome this limitation we studied the feasibility of the use of cyclodextrins (CDs) as solubility-enhancing agents. CDs are natural macrocyclic oligomers composed of α-<span style="font-variant: small-caps;">d</span>-glucose units linked by α-1,4 glycosidic bonds to form torus-shaped molecules, responsible for inclusion complex formation with organic molecules. In particular, the aim of this study was to evaluate the feasibility of complexation between PTB and native CDs using various preparative methods. The isolated solid products were characterized using differential scanning calorimetry (DSC), simultaneous thermogravimetric/DSC analysis (TGA/DSC), Fourier transform infrared (FT-IR) spectroscopy, and X-ray diffraction (XRD) on powder and single crystals. The results indicated little or no evidence of the affinity of PTB to complex with α-CD using the kneading method. However, with β-CD and γ-CD thermal analysis revealed an interaction which was also corroborated by FT-IR and <sup>1</sup>H-NMR spectroscopy. With β-CD, a hydrated complex of PTB was isolated and its characterization by single-crystal XRD revealed, for the first time, the mode of inclusion of the PTB molecule in the cavity of a CD. To complement the solid-state data, liquid-phase studies were carried out to establish the effect of CDs on the aqueous solubility of PTB and to determine the complex stoichiometries and the association constants for complex formation. Phase-solubility studies showed A<sub>L</sub>-type profiles for α- and β-CD and a B<sub>S</sub> profile for γ-CD, with K<sub>1:1</sub> values of 1144, 4950, and 133 M<sup>−1</sup> for α-CD·PTB, β-CD·PTB, and γ-CD·PTB, respectively. The stoichiometry of CD·PTB complexes, determined by Job’s method, revealed for each system a 1:1 molar ratio. The dissolution rate of PTB was approximately doubled just by employing simple physical mixtures, but the best performance was achieved by products obtained via kneading and co-precipitation, which effected the complete dissolution of PTB in 40 and 20 min for β-CD and γ-CD, respectively.https://www.mdpi.com/1999-4923/14/1/8pterostilbenecyclodextrincomplexationthermal analysisX-ray diffraction |
| spellingShingle | Laura Catenacci Alexios I. Vicatos Milena Sorrenti Maria Cristina Bonferoni Mino R. Caira Native Cyclodextrins as Complexation Agents for Pterostilbene: Complex Preparation and Characterization in Solution and in the Solid State Pharmaceutics pterostilbene cyclodextrin complexation thermal analysis X-ray diffraction |
| title | Native Cyclodextrins as Complexation Agents for Pterostilbene: Complex Preparation and Characterization in Solution and in the Solid State |
| title_full | Native Cyclodextrins as Complexation Agents for Pterostilbene: Complex Preparation and Characterization in Solution and in the Solid State |
| title_fullStr | Native Cyclodextrins as Complexation Agents for Pterostilbene: Complex Preparation and Characterization in Solution and in the Solid State |
| title_full_unstemmed | Native Cyclodextrins as Complexation Agents for Pterostilbene: Complex Preparation and Characterization in Solution and in the Solid State |
| title_short | Native Cyclodextrins as Complexation Agents for Pterostilbene: Complex Preparation and Characterization in Solution and in the Solid State |
| title_sort | native cyclodextrins as complexation agents for pterostilbene complex preparation and characterization in solution and in the solid state |
| topic | pterostilbene cyclodextrin complexation thermal analysis X-ray diffraction |
| url | https://www.mdpi.com/1999-4923/14/1/8 |
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