Solid Dispersions of Gefitinib with D-<i>α</i>-Tocopherol Polyethylene Glycol-1000 Succinate and 2-Hydroxypropyl <i>β</i>-Cyclodextrin Complex Improved Their Solubility, Dissolution and Apoptosis against A549 Cells
This study focuses on the development and characterization of solid dispersions (SDs) of Gefitinib (GEF) to improve its aqueous solubility and therapeutic activity against lung cancer. SDs were prepared by the co-precipitation method with tocopheryl-polyethylene-glycol succinate-1000 (TPGS) (F1), so...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-09-01
|
| Series: | Applied Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-3417/13/19/10859 |
| _version_ | 1797576189653549056 |
|---|---|
| author | Mohd Abul Kalam Adel Ali Alhowyan Sulaiman S. Alhudaithi Mohd Shahnawaz Khan Abdullah K. Alshememry Musaed Alkholief |
| author_facet | Mohd Abul Kalam Adel Ali Alhowyan Sulaiman S. Alhudaithi Mohd Shahnawaz Khan Abdullah K. Alshememry Musaed Alkholief |
| author_sort | Mohd Abul Kalam |
| collection | DOAJ |
| description | This study focuses on the development and characterization of solid dispersions (SDs) of Gefitinib (GEF) to improve its aqueous solubility and therapeutic activity against lung cancer. SDs were prepared by the co-precipitation method with tocopheryl-polyethylene-glycol succinate-1000 (TPGS) (F1), sodium lauryl sulfate (SLS) (F2) and complexation of F1 with hydroxypropyl <i>β</i>-cyclodextrin (HP-<i>β</i>-CD) (F3). Optimal formulations (F1 and F3) were used against A549 cells to determine the apoptosis, expressions of p53 and caspases. F3 has shown the highest solubility (1271.21 µg/mL), followed by F1 (1003.69 µg/mL), F2 (707.81 µg/mL) and GEF pure (303.85 µg/mL) in 0.1N HCl. Dissolution at 1.2 pH significantly enhanced the release from F3 (99.19%), followed by F1 (94.76%), F2 (85.70%) and GEF pure (37.26%) during 120 min. Complexation of GEF–TPGS with HP-<i>β</i>-CD significantly improved drug release with high dissolution efficiency (78.57%) in 24.9 min of mean dissolution time. Differential scanning calorimetry revealed crystalline to amorphous conversion of GEF in SDs, which was confirmed by scanning electron microscopy. Fourier transform infrared and proton nuclear magnetic resonance spectral analysis revealed no interaction between GEF and excipients. The IC<sub>50</sub> values were 2.239, 3.135 and 4.471 µM for F3, F1 and GEF pure, respectively, against A549 cells. Increased expressions of p53 (5.9-, 4.6- and 3.04-fold), caspase-3 (5.38-, 3.78- and 3.01-fold) and caspase-9 (5.35-, 3.76- and 2.47-fold) in the case of F3, F1 and GEF pure, respectively, as compared to the untreated A549 cells indicated improved apoptotic potential of the SDs. TPGS SDs and their complexation with HP-<i>β</i>-CD improved the solubility, dissolution and efficacy of GEF against A549 cells. So, they can be a suitable alternative to the conventional GEF formulations against non-small-cell lung cancers. |
| first_indexed | 2024-03-10T21:49:41Z |
| format | Article |
| id | doaj.art-8864a880d94f4ae3a04a364aed5f6769 |
| institution | Directory Open Access Journal |
| issn | 2076-3417 |
| language | English |
| last_indexed | 2024-03-10T21:49:41Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Applied Sciences |
| spelling | doaj.art-8864a880d94f4ae3a04a364aed5f67692023-11-19T14:05:11ZengMDPI AGApplied Sciences2076-34172023-09-0113191085910.3390/app131910859Solid Dispersions of Gefitinib with D-<i>α</i>-Tocopherol Polyethylene Glycol-1000 Succinate and 2-Hydroxypropyl <i>β</i>-Cyclodextrin Complex Improved Their Solubility, Dissolution and Apoptosis against A549 CellsMohd Abul Kalam0Adel Ali Alhowyan1Sulaiman S. Alhudaithi2Mohd Shahnawaz Khan3Abdullah K. Alshememry4Musaed Alkholief5Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Biochemistry, College of Science, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaThis study focuses on the development and characterization of solid dispersions (SDs) of Gefitinib (GEF) to improve its aqueous solubility and therapeutic activity against lung cancer. SDs were prepared by the co-precipitation method with tocopheryl-polyethylene-glycol succinate-1000 (TPGS) (F1), sodium lauryl sulfate (SLS) (F2) and complexation of F1 with hydroxypropyl <i>β</i>-cyclodextrin (HP-<i>β</i>-CD) (F3). Optimal formulations (F1 and F3) were used against A549 cells to determine the apoptosis, expressions of p53 and caspases. F3 has shown the highest solubility (1271.21 µg/mL), followed by F1 (1003.69 µg/mL), F2 (707.81 µg/mL) and GEF pure (303.85 µg/mL) in 0.1N HCl. Dissolution at 1.2 pH significantly enhanced the release from F3 (99.19%), followed by F1 (94.76%), F2 (85.70%) and GEF pure (37.26%) during 120 min. Complexation of GEF–TPGS with HP-<i>β</i>-CD significantly improved drug release with high dissolution efficiency (78.57%) in 24.9 min of mean dissolution time. Differential scanning calorimetry revealed crystalline to amorphous conversion of GEF in SDs, which was confirmed by scanning electron microscopy. Fourier transform infrared and proton nuclear magnetic resonance spectral analysis revealed no interaction between GEF and excipients. The IC<sub>50</sub> values were 2.239, 3.135 and 4.471 µM for F3, F1 and GEF pure, respectively, against A549 cells. Increased expressions of p53 (5.9-, 4.6- and 3.04-fold), caspase-3 (5.38-, 3.78- and 3.01-fold) and caspase-9 (5.35-, 3.76- and 2.47-fold) in the case of F3, F1 and GEF pure, respectively, as compared to the untreated A549 cells indicated improved apoptotic potential of the SDs. TPGS SDs and their complexation with HP-<i>β</i>-CD improved the solubility, dissolution and efficacy of GEF against A549 cells. So, they can be a suitable alternative to the conventional GEF formulations against non-small-cell lung cancers.https://www.mdpi.com/2076-3417/13/19/10859GefitinibTPGSsolid dispersionsHP <i>β</i>-CDlung cancerA549 cells |
| spellingShingle | Mohd Abul Kalam Adel Ali Alhowyan Sulaiman S. Alhudaithi Mohd Shahnawaz Khan Abdullah K. Alshememry Musaed Alkholief Solid Dispersions of Gefitinib with D-<i>α</i>-Tocopherol Polyethylene Glycol-1000 Succinate and 2-Hydroxypropyl <i>β</i>-Cyclodextrin Complex Improved Their Solubility, Dissolution and Apoptosis against A549 Cells Applied Sciences Gefitinib TPGS solid dispersions HP <i>β</i>-CD lung cancer A549 cells |
| title | Solid Dispersions of Gefitinib with D-<i>α</i>-Tocopherol Polyethylene Glycol-1000 Succinate and 2-Hydroxypropyl <i>β</i>-Cyclodextrin Complex Improved Their Solubility, Dissolution and Apoptosis against A549 Cells |
| title_full | Solid Dispersions of Gefitinib with D-<i>α</i>-Tocopherol Polyethylene Glycol-1000 Succinate and 2-Hydroxypropyl <i>β</i>-Cyclodextrin Complex Improved Their Solubility, Dissolution and Apoptosis against A549 Cells |
| title_fullStr | Solid Dispersions of Gefitinib with D-<i>α</i>-Tocopherol Polyethylene Glycol-1000 Succinate and 2-Hydroxypropyl <i>β</i>-Cyclodextrin Complex Improved Their Solubility, Dissolution and Apoptosis against A549 Cells |
| title_full_unstemmed | Solid Dispersions of Gefitinib with D-<i>α</i>-Tocopherol Polyethylene Glycol-1000 Succinate and 2-Hydroxypropyl <i>β</i>-Cyclodextrin Complex Improved Their Solubility, Dissolution and Apoptosis against A549 Cells |
| title_short | Solid Dispersions of Gefitinib with D-<i>α</i>-Tocopherol Polyethylene Glycol-1000 Succinate and 2-Hydroxypropyl <i>β</i>-Cyclodextrin Complex Improved Their Solubility, Dissolution and Apoptosis against A549 Cells |
| title_sort | solid dispersions of gefitinib with d i α i tocopherol polyethylene glycol 1000 succinate and 2 hydroxypropyl i β i cyclodextrin complex improved their solubility dissolution and apoptosis against a549 cells |
| topic | Gefitinib TPGS solid dispersions HP <i>β</i>-CD lung cancer A549 cells |
| url | https://www.mdpi.com/2076-3417/13/19/10859 |
| work_keys_str_mv | AT mohdabulkalam soliddispersionsofgefitinibwithdiaitocopherolpolyethyleneglycol1000succinateand2hydroxypropylibicyclodextrincompleximprovedtheirsolubilitydissolutionandapoptosisagainsta549cells AT adelalialhowyan soliddispersionsofgefitinibwithdiaitocopherolpolyethyleneglycol1000succinateand2hydroxypropylibicyclodextrincompleximprovedtheirsolubilitydissolutionandapoptosisagainsta549cells AT sulaimansalhudaithi soliddispersionsofgefitinibwithdiaitocopherolpolyethyleneglycol1000succinateand2hydroxypropylibicyclodextrincompleximprovedtheirsolubilitydissolutionandapoptosisagainsta549cells AT mohdshahnawazkhan soliddispersionsofgefitinibwithdiaitocopherolpolyethyleneglycol1000succinateand2hydroxypropylibicyclodextrincompleximprovedtheirsolubilitydissolutionandapoptosisagainsta549cells AT abdullahkalshememry soliddispersionsofgefitinibwithdiaitocopherolpolyethyleneglycol1000succinateand2hydroxypropylibicyclodextrincompleximprovedtheirsolubilitydissolutionandapoptosisagainsta549cells AT musaedalkholief soliddispersionsofgefitinibwithdiaitocopherolpolyethyleneglycol1000succinateand2hydroxypropylibicyclodextrincompleximprovedtheirsolubilitydissolutionandapoptosisagainsta549cells |