Comparison of Drug Delivery Systems with Different Types of Nanoparticles in Terms of Cellular Uptake and Responses in Human Endothelial Cells, Pericytes, and Astrocytes
<b>Background/Objectives</b>: The key components of the blood–brain barrier (BBB) are endothelial cells, pericytes, astrocytes, and the capillary basement membrane. The BBB serves as the main barrier for drug delivery to the brain and is the most restrictive endothelial barrier in the bo...
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MDPI AG
2024-11-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/17/12/1567 |
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| author | Hakan Sahin Oguz Yucel Paul Holloway Eren Yildirim Serkan Emik Gulten Gurdag Gamze Tanriverdi Gozde Erkanli Senturk |
| author_facet | Hakan Sahin Oguz Yucel Paul Holloway Eren Yildirim Serkan Emik Gulten Gurdag Gamze Tanriverdi Gozde Erkanli Senturk |
| author_sort | Hakan Sahin |
| collection | DOAJ |
| description | <b>Background/Objectives</b>: The key components of the blood–brain barrier (BBB) are endothelial cells, pericytes, astrocytes, and the capillary basement membrane. The BBB serves as the main barrier for drug delivery to the brain and is the most restrictive endothelial barrier in the body. Nearly all large therapeutic molecules and over 90% of small-molecule drugs cannot cross the BBB. To overcome this challenge, nanotechnology, particularly drug delivery systems such as nanoparticles (NPs), have gained significant attention. <b>Methods</b>: Poly(lactide-<i>co</i>-glycolide) (PLGA) and albumin-based NPs (bovine/human), with or without transferrin (Tf) ligands (BSA, HSA, BSA-Tf, HSA-Tf), and nanolipid carriers (NLC) were synthesized. The interactions of these NPs with human brain microvascular endothelial cells (hBMECs), human brain vascular pericytes (hBVPs), and human astrocytes (hASTROs) were analyzed. <b>Results</b>: At doses of 15.62 µg/mL, 31.25 µg/mL, and 62.5 µg/mL, none of the NPs caused toxic effects on hBMECs, hBVPs, or hASTROs after 3 h of incubation. All NPs were internalized by the cells, but BSA-Tf and HSA-Tf showed significantly higher uptake in hBMECs in a dose-dependent manner. Ultrastructural analysis revealed notable differences between NP formulation and cell type. <b>Conclusions</b>: Our findings underscore the potential of ligand-targeted NPs to selectively interact with BBB endothelial cells. Ultrastructural analysis reveals distinct cellular processing pathways for various NP formulations across BBB-associated cell types, with autophagy emerging as a crucial mechanism for NP handling in pericytes and astrocytes. Changes in NP chemical properties upon biological exposure present significant challenges for nanomedicine design, emphasizing the need for further investigation into NP interactions at the cellular and subcellular levels. |
| format | Article |
| id | doaj-art-a3c07af45d3c4fd6a7c461c4f81e4295 |
| institution | Kabale University |
| issn | 1424-8247 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj-art-a3c07af45d3c4fd6a7c461c4f81e42952024-12-27T14:45:43ZengMDPI AGPharmaceuticals1424-82472024-11-011712156710.3390/ph17121567Comparison of Drug Delivery Systems with Different Types of Nanoparticles in Terms of Cellular Uptake and Responses in Human Endothelial Cells, Pericytes, and AstrocytesHakan Sahin0Oguz Yucel1Paul Holloway2Eren Yildirim3Serkan Emik4Gulten Gurdag5Gamze Tanriverdi6Gozde Erkanli Senturk7Department of Histology and Embryology, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul 34098, TurkeyDepartment of Chemical Engineering, Faculty of Engineering, Istanbul University-Cerrahpasa, Istanbul 34320, TurkeyRadcliffe Department of Medicine, University of Oxford, Oxford OX3 9DU, UKDepartment of Chemical Engineering, Faculty of Engineering, Istanbul University-Cerrahpasa, Istanbul 34320, TurkeyDepartment of Chemical Engineering, Faculty of Engineering, Istanbul University-Cerrahpasa, Istanbul 34320, TurkeyDepartment of Chemical Engineering, Faculty of Engineering, Istanbul University-Cerrahpasa, Istanbul 34320, TurkeyDepartment of Histology and Embryology, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul 34098, TurkeyDepartment of Histology and Embryology, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul 34098, Turkey<b>Background/Objectives</b>: The key components of the blood–brain barrier (BBB) are endothelial cells, pericytes, astrocytes, and the capillary basement membrane. The BBB serves as the main barrier for drug delivery to the brain and is the most restrictive endothelial barrier in the body. Nearly all large therapeutic molecules and over 90% of small-molecule drugs cannot cross the BBB. To overcome this challenge, nanotechnology, particularly drug delivery systems such as nanoparticles (NPs), have gained significant attention. <b>Methods</b>: Poly(lactide-<i>co</i>-glycolide) (PLGA) and albumin-based NPs (bovine/human), with or without transferrin (Tf) ligands (BSA, HSA, BSA-Tf, HSA-Tf), and nanolipid carriers (NLC) were synthesized. The interactions of these NPs with human brain microvascular endothelial cells (hBMECs), human brain vascular pericytes (hBVPs), and human astrocytes (hASTROs) were analyzed. <b>Results</b>: At doses of 15.62 µg/mL, 31.25 µg/mL, and 62.5 µg/mL, none of the NPs caused toxic effects on hBMECs, hBVPs, or hASTROs after 3 h of incubation. All NPs were internalized by the cells, but BSA-Tf and HSA-Tf showed significantly higher uptake in hBMECs in a dose-dependent manner. Ultrastructural analysis revealed notable differences between NP formulation and cell type. <b>Conclusions</b>: Our findings underscore the potential of ligand-targeted NPs to selectively interact with BBB endothelial cells. Ultrastructural analysis reveals distinct cellular processing pathways for various NP formulations across BBB-associated cell types, with autophagy emerging as a crucial mechanism for NP handling in pericytes and astrocytes. Changes in NP chemical properties upon biological exposure present significant challenges for nanomedicine design, emphasizing the need for further investigation into NP interactions at the cellular and subcellular levels.https://www.mdpi.com/1424-8247/17/12/1567drug delivery systempoly(lactide-<i>co</i>-glycolide)bovine serum albuminhuman serum albuminnanolipid carriersendothelial cell |
| spellingShingle | Hakan Sahin Oguz Yucel Paul Holloway Eren Yildirim Serkan Emik Gulten Gurdag Gamze Tanriverdi Gozde Erkanli Senturk Comparison of Drug Delivery Systems with Different Types of Nanoparticles in Terms of Cellular Uptake and Responses in Human Endothelial Cells, Pericytes, and Astrocytes Pharmaceuticals drug delivery system poly(lactide-<i>co</i>-glycolide) bovine serum albumin human serum albumin nanolipid carriers endothelial cell |
| title | Comparison of Drug Delivery Systems with Different Types of Nanoparticles in Terms of Cellular Uptake and Responses in Human Endothelial Cells, Pericytes, and Astrocytes |
| title_full | Comparison of Drug Delivery Systems with Different Types of Nanoparticles in Terms of Cellular Uptake and Responses in Human Endothelial Cells, Pericytes, and Astrocytes |
| title_fullStr | Comparison of Drug Delivery Systems with Different Types of Nanoparticles in Terms of Cellular Uptake and Responses in Human Endothelial Cells, Pericytes, and Astrocytes |
| title_full_unstemmed | Comparison of Drug Delivery Systems with Different Types of Nanoparticles in Terms of Cellular Uptake and Responses in Human Endothelial Cells, Pericytes, and Astrocytes |
| title_short | Comparison of Drug Delivery Systems with Different Types of Nanoparticles in Terms of Cellular Uptake and Responses in Human Endothelial Cells, Pericytes, and Astrocytes |
| title_sort | comparison of drug delivery systems with different types of nanoparticles in terms of cellular uptake and responses in human endothelial cells pericytes and astrocytes |
| topic | drug delivery system poly(lactide-<i>co</i>-glycolide) bovine serum albumin human serum albumin nanolipid carriers endothelial cell |
| url | https://www.mdpi.com/1424-8247/17/12/1567 |
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