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Phloretin Transfersomes for Transdermal Delivery: Design, Optimization, and In Vivo Evaluation
Background: Phloretin (Phl) is a flavonoid compound that contains multiple phenolic hydroxyl groups. It is found in many plants, such as apple leaves, lychee pericarp, and begonia, and has various biological activities, such as antioxidant and anticancer effects. The strong hydrogen bonding between...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10574780/ https://www.ncbi.nlm.nih.gov/pubmed/37836633 http://dx.doi.org/10.3390/molecules28196790 |
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author | Wang, Jiawen Zhao, Yuanyuan Zhai, Bingtao Cheng, Jiangxue Sun, Jing Zhang, Xiaofei Guo, Dongyan |
author_facet | Wang, Jiawen Zhao, Yuanyuan Zhai, Bingtao Cheng, Jiangxue Sun, Jing Zhang, Xiaofei Guo, Dongyan |
author_sort | Wang, Jiawen |
collection | PubMed |
description | Background: Phloretin (Phl) is a flavonoid compound that contains multiple phenolic hydroxyl groups. It is found in many plants, such as apple leaves, lychee pericarp, and begonia, and has various biological activities, such as antioxidant and anticancer effects. The strong hydrogen bonding between Phl molecules results in poor water solubility and low bioavailability, and thus the scope of the clinical application of Phl is limited. Therefore, it is particularly important to improve the water solubility of Phl for its use to further combat or alleviate skin aging and oxidative damage and develop antioxidant products for the skin. The purpose of this study was to develop and evaluate a phloretin transfersome gel (PTG) preparation for transdermal drug delivery to improve the bioavailability of the drug and delay aging. Methods: Phloretin transfersomes (Phl-TFs) were prepared and optimized by the thin-film dispersion–ultrasonication method. Phl-TFs were characterized by transmission electron microscopy (TEM), differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy, and X-ray diffraction (XRD). The Log P method was used to determine the solubility of the Phl-TFs. The skin penetration ability of the prepared PTG was evaluated using the Franz diffusion cell method. In addition, the in vivo pharmacokinetics of PTG were studied in rats, and an antioxidant activity investigation was conducted using a D-gal rat model. Results: Phl-TFs were successfully prepared with a Soybean Phosphatidylcholine (SPC)/CHOL ratio of 2.7:1 w/v, a phloretin concentration of 1.3 mg/mL, a hydration time of 46 min, an ultrasound time of 5 min, and an ultrasound power of 180 W. The Log P was 2.26, which was significantly higher than that of phloretin (p < 0.05, paired t test). The results of the in vitro penetration test demonstrated that the cumulative skin penetration of the Phl-TFs after 24 h was 842.73 ± 20.86 μg/cm(2). The data from an in vivo pharmacokinetic study showed that the C(max) and AUC of PTG were 1.39- and 1.97-fold higher than those of the phloretin solution gel (PSG), respectively (p < 0.05, paired t test). The experimental results in aging rats showed that PTG had a better antioxidant effect. Conclusions: Phl-TFs and PTG preparations with a good shape, safety, and stability were successfully prepared. In vivo pharmacokinetics and preliminary antioxidant experiments further verified the transdermal penetration and antioxidant activity of the phloretin transdermal drug delivery preparation, providing an experimental basis for its further development. |
format | Online Article Text |
id | pubmed-10574780 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-105747802023-10-14 Phloretin Transfersomes for Transdermal Delivery: Design, Optimization, and In Vivo Evaluation Wang, Jiawen Zhao, Yuanyuan Zhai, Bingtao Cheng, Jiangxue Sun, Jing Zhang, Xiaofei Guo, Dongyan Molecules Article Background: Phloretin (Phl) is a flavonoid compound that contains multiple phenolic hydroxyl groups. It is found in many plants, such as apple leaves, lychee pericarp, and begonia, and has various biological activities, such as antioxidant and anticancer effects. The strong hydrogen bonding between Phl molecules results in poor water solubility and low bioavailability, and thus the scope of the clinical application of Phl is limited. Therefore, it is particularly important to improve the water solubility of Phl for its use to further combat or alleviate skin aging and oxidative damage and develop antioxidant products for the skin. The purpose of this study was to develop and evaluate a phloretin transfersome gel (PTG) preparation for transdermal drug delivery to improve the bioavailability of the drug and delay aging. Methods: Phloretin transfersomes (Phl-TFs) were prepared and optimized by the thin-film dispersion–ultrasonication method. Phl-TFs were characterized by transmission electron microscopy (TEM), differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy, and X-ray diffraction (XRD). The Log P method was used to determine the solubility of the Phl-TFs. The skin penetration ability of the prepared PTG was evaluated using the Franz diffusion cell method. In addition, the in vivo pharmacokinetics of PTG were studied in rats, and an antioxidant activity investigation was conducted using a D-gal rat model. Results: Phl-TFs were successfully prepared with a Soybean Phosphatidylcholine (SPC)/CHOL ratio of 2.7:1 w/v, a phloretin concentration of 1.3 mg/mL, a hydration time of 46 min, an ultrasound time of 5 min, and an ultrasound power of 180 W. The Log P was 2.26, which was significantly higher than that of phloretin (p < 0.05, paired t test). The results of the in vitro penetration test demonstrated that the cumulative skin penetration of the Phl-TFs after 24 h was 842.73 ± 20.86 μg/cm(2). The data from an in vivo pharmacokinetic study showed that the C(max) and AUC of PTG were 1.39- and 1.97-fold higher than those of the phloretin solution gel (PSG), respectively (p < 0.05, paired t test). The experimental results in aging rats showed that PTG had a better antioxidant effect. Conclusions: Phl-TFs and PTG preparations with a good shape, safety, and stability were successfully prepared. In vivo pharmacokinetics and preliminary antioxidant experiments further verified the transdermal penetration and antioxidant activity of the phloretin transdermal drug delivery preparation, providing an experimental basis for its further development. MDPI 2023-09-24 /pmc/articles/PMC10574780/ /pubmed/37836633 http://dx.doi.org/10.3390/molecules28196790 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Wang, Jiawen Zhao, Yuanyuan Zhai, Bingtao Cheng, Jiangxue Sun, Jing Zhang, Xiaofei Guo, Dongyan Phloretin Transfersomes for Transdermal Delivery: Design, Optimization, and In Vivo Evaluation |
title | Phloretin Transfersomes for Transdermal Delivery: Design, Optimization, and In Vivo Evaluation |
title_full | Phloretin Transfersomes for Transdermal Delivery: Design, Optimization, and In Vivo Evaluation |
title_fullStr | Phloretin Transfersomes for Transdermal Delivery: Design, Optimization, and In Vivo Evaluation |
title_full_unstemmed | Phloretin Transfersomes for Transdermal Delivery: Design, Optimization, and In Vivo Evaluation |
title_short | Phloretin Transfersomes for Transdermal Delivery: Design, Optimization, and In Vivo Evaluation |
title_sort | phloretin transfersomes for transdermal delivery: design, optimization, and in vivo evaluation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10574780/ https://www.ncbi.nlm.nih.gov/pubmed/37836633 http://dx.doi.org/10.3390/molecules28196790 |
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