Increased/Targeted Brain (Pro)Drug Delivery via Utilization of Solute Carriers (SLCs)
Membrane transporters have a crucial role in compounds’ brain drug delivery. They allow not only the penetration of a wide variety of different compounds to cross the endothelial cells of the blood–brain barrier (BBB), but also the accumulation of them into the brain parenchymal cells. Solute carrie...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-06-01
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| Series: | Pharmaceutics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4923/14/6/1234 |
| _version_ | 1797483250157879296 |
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| author | Johanna Huttunen Santosh Kumar Adla Magdalena Markowicz-Piasecka Kristiina M. Huttunen |
| author_facet | Johanna Huttunen Santosh Kumar Adla Magdalena Markowicz-Piasecka Kristiina M. Huttunen |
| author_sort | Johanna Huttunen |
| collection | DOAJ |
| description | Membrane transporters have a crucial role in compounds’ brain drug delivery. They allow not only the penetration of a wide variety of different compounds to cross the endothelial cells of the blood–brain barrier (BBB), but also the accumulation of them into the brain parenchymal cells. Solute carriers (SLCs), with nearly 500 family members, are the largest group of membrane transporters. Unfortunately, not all SLCs are fully characterized and used in rational drug design. However, if the structural features for transporter interactions (binding and translocation) are known, a prodrug approach can be utilized to temporarily change the pharmacokinetics and brain delivery properties of almost any compound. In this review, main transporter subtypes that are participating in brain drug disposition or have been used to improve brain drug delivery across the BBB via the prodrug approach, are introduced. Moreover, the ability of selected transporters to be utilized in intrabrain drug delivery is discussed. Thus, this comprehensive review will give insights into the methods, such as computational drug design, that should be utilized more effectively to understand the detailed transport mechanisms. Moreover, factors, such as transporter expression modulation pathways in diseases that should be taken into account in rational (pro)drug development, are considered to achieve successful clinical applications in the future. |
| first_indexed | 2024-03-09T22:45:15Z |
| format | Article |
| id | doaj.art-2d786106ae254fe3805260edccb678c3 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T22:45:15Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-2d786106ae254fe3805260edccb678c32023-11-23T18:30:26ZengMDPI AGPharmaceutics1999-49232022-06-01146123410.3390/pharmaceutics14061234Increased/Targeted Brain (Pro)Drug Delivery via Utilization of Solute Carriers (SLCs)Johanna Huttunen0Santosh Kumar Adla1Magdalena Markowicz-Piasecka2Kristiina M. Huttunen3School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, FinlandSchool of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, FinlandDepartment of Pharmaceutical Chemistry, Drug Analysis and Radiopharmacy, Medical University of Lodz, ul. Muszyńskiego 1, 90-151 Lodz, PolandSchool of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, FinlandMembrane transporters have a crucial role in compounds’ brain drug delivery. They allow not only the penetration of a wide variety of different compounds to cross the endothelial cells of the blood–brain barrier (BBB), but also the accumulation of them into the brain parenchymal cells. Solute carriers (SLCs), with nearly 500 family members, are the largest group of membrane transporters. Unfortunately, not all SLCs are fully characterized and used in rational drug design. However, if the structural features for transporter interactions (binding and translocation) are known, a prodrug approach can be utilized to temporarily change the pharmacokinetics and brain delivery properties of almost any compound. In this review, main transporter subtypes that are participating in brain drug disposition or have been used to improve brain drug delivery across the BBB via the prodrug approach, are introduced. Moreover, the ability of selected transporters to be utilized in intrabrain drug delivery is discussed. Thus, this comprehensive review will give insights into the methods, such as computational drug design, that should be utilized more effectively to understand the detailed transport mechanisms. Moreover, factors, such as transporter expression modulation pathways in diseases that should be taken into account in rational (pro)drug development, are considered to achieve successful clinical applications in the future.https://www.mdpi.com/1999-4923/14/6/1234blood–brain barrier (BBB)brain drug deliveryprodrugssolute carriers (SLCs) |
| spellingShingle | Johanna Huttunen Santosh Kumar Adla Magdalena Markowicz-Piasecka Kristiina M. Huttunen Increased/Targeted Brain (Pro)Drug Delivery via Utilization of Solute Carriers (SLCs) Pharmaceutics blood–brain barrier (BBB) brain drug delivery prodrugs solute carriers (SLCs) |
| title | Increased/Targeted Brain (Pro)Drug Delivery via Utilization of Solute Carriers (SLCs) |
| title_full | Increased/Targeted Brain (Pro)Drug Delivery via Utilization of Solute Carriers (SLCs) |
| title_fullStr | Increased/Targeted Brain (Pro)Drug Delivery via Utilization of Solute Carriers (SLCs) |
| title_full_unstemmed | Increased/Targeted Brain (Pro)Drug Delivery via Utilization of Solute Carriers (SLCs) |
| title_short | Increased/Targeted Brain (Pro)Drug Delivery via Utilization of Solute Carriers (SLCs) |
| title_sort | increased targeted brain pro drug delivery via utilization of solute carriers slcs |
| topic | blood–brain barrier (BBB) brain drug delivery prodrugs solute carriers (SLCs) |
| url | https://www.mdpi.com/1999-4923/14/6/1234 |
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