The Study of Cyclosporin A Nanocrystals Uptake and Transport across an Intestinal Epithelial Cell Model
Cyclosporin A nanocrystals (CsA-NCs) interaction with Caco-2 cells were investigated in this study, including cellular uptake and transport across Caco-2 cell monolayers. CsA-NCs of 165 nm, 240 nm and 450 nm were formulated. The dissolution of CsA-NCs was investigated by paddle method. The effect of...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-05-01
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| Series: | Polymers |
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| Online Access: | https://www.mdpi.com/2073-4360/14/10/1975 |
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| author | Wenjun Sun Yang Tian Zengming Wang Hui Zhang Aiping Zheng |
| author_facet | Wenjun Sun Yang Tian Zengming Wang Hui Zhang Aiping Zheng |
| author_sort | Wenjun Sun |
| collection | DOAJ |
| description | Cyclosporin A nanocrystals (CsA-NCs) interaction with Caco-2 cells were investigated in this study, including cellular uptake and transport across Caco-2 cell monolayers. CsA-NCs of 165 nm, 240 nm and 450 nm were formulated. The dissolution of CsA-NCs was investigated by paddle method. The effect of size, concentration and incubation time on cellular uptake and dissolution kinetics of CsA-NCs in cells were studied. Uptake mechanisms were also evaluated using endocytotic inhibitors and low temperature (4 °C). The cell monolayers were incubated with each diameter CsA-NCs to evaluate the effect of size on the permeation characteristics of CsA across the intestinal mucosa. The results of dissolution study showed that 165 nm CsA-NC had the highest dissolution rate followed by 240 CsA-NC and finally 450 nm CsA-NC. The saturation of cell uptake of CsA-NCs was observed with the increase of incubation concentration and time. 240 nm and 450 nm CsA-NCs had the lowest and highest uptake efficiency at different time and drug concentration, respectively. The uptake of all three-sized CsA-NCs declined significantly in some different degree after the pre-treatment with different endocytosis inhibitors. 165 nm CsA-NC showed a highest transport capacity across monolayers at the same concentration and time. The results suggest that the size of CsA-NCs can not only affect the efficiency of cellular uptake, but also the type of endocytosis. Decreasing particle size of CsA-NCs can improve transport capacity of CsA through cell monolayer. |
| first_indexed | 2024-03-10T03:01:57Z |
| format | Article |
| id | doaj.art-9af26e275ddc4e2cb8352d9d1d77ab9e |
| institution | Directory Open Access Journal |
| issn | 2073-4360 |
| language | English |
| last_indexed | 2024-03-10T03:01:57Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Polymers |
| spelling | doaj.art-9af26e275ddc4e2cb8352d9d1d77ab9e2023-11-23T12:45:22ZengMDPI AGPolymers2073-43602022-05-011410197510.3390/polym14101975The Study of Cyclosporin A Nanocrystals Uptake and Transport across an Intestinal Epithelial Cell ModelWenjun Sun0Yang Tian1Zengming Wang2Hui Zhang3Aiping Zheng4Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, ChinaInstitute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, ChinaInstitute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, ChinaInstitute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, ChinaInstitute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, ChinaCyclosporin A nanocrystals (CsA-NCs) interaction with Caco-2 cells were investigated in this study, including cellular uptake and transport across Caco-2 cell monolayers. CsA-NCs of 165 nm, 240 nm and 450 nm were formulated. The dissolution of CsA-NCs was investigated by paddle method. The effect of size, concentration and incubation time on cellular uptake and dissolution kinetics of CsA-NCs in cells were studied. Uptake mechanisms were also evaluated using endocytotic inhibitors and low temperature (4 °C). The cell monolayers were incubated with each diameter CsA-NCs to evaluate the effect of size on the permeation characteristics of CsA across the intestinal mucosa. The results of dissolution study showed that 165 nm CsA-NC had the highest dissolution rate followed by 240 CsA-NC and finally 450 nm CsA-NC. The saturation of cell uptake of CsA-NCs was observed with the increase of incubation concentration and time. 240 nm and 450 nm CsA-NCs had the lowest and highest uptake efficiency at different time and drug concentration, respectively. The uptake of all three-sized CsA-NCs declined significantly in some different degree after the pre-treatment with different endocytosis inhibitors. 165 nm CsA-NC showed a highest transport capacity across monolayers at the same concentration and time. The results suggest that the size of CsA-NCs can not only affect the efficiency of cellular uptake, but also the type of endocytosis. Decreasing particle size of CsA-NCs can improve transport capacity of CsA through cell monolayer.https://www.mdpi.com/2073-4360/14/10/1975cyclosporin A nanocrystalsendocytosis inhibitorcellular uptakeCaco-2 cell monolayer |
| spellingShingle | Wenjun Sun Yang Tian Zengming Wang Hui Zhang Aiping Zheng The Study of Cyclosporin A Nanocrystals Uptake and Transport across an Intestinal Epithelial Cell Model Polymers cyclosporin A nanocrystals endocytosis inhibitor cellular uptake Caco-2 cell monolayer |
| title | The Study of Cyclosporin A Nanocrystals Uptake and Transport across an Intestinal Epithelial Cell Model |
| title_full | The Study of Cyclosporin A Nanocrystals Uptake and Transport across an Intestinal Epithelial Cell Model |
| title_fullStr | The Study of Cyclosporin A Nanocrystals Uptake and Transport across an Intestinal Epithelial Cell Model |
| title_full_unstemmed | The Study of Cyclosporin A Nanocrystals Uptake and Transport across an Intestinal Epithelial Cell Model |
| title_short | The Study of Cyclosporin A Nanocrystals Uptake and Transport across an Intestinal Epithelial Cell Model |
| title_sort | study of cyclosporin a nanocrystals uptake and transport across an intestinal epithelial cell model |
| topic | cyclosporin A nanocrystals endocytosis inhibitor cellular uptake Caco-2 cell monolayer |
| url | https://www.mdpi.com/2073-4360/14/10/1975 |
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