Increased/Targeted Brain (Pro)Drug Delivery via Utilization of Solute Carriers (SLCs)

0558866 - ÚOCHB 2023 RIV CH eng J - Článek v odborném periodiku
Huttunen, J. - Adla, Santosh Kumar - Markowicz-Piasecka, M. - Huttunen, K. M.
Increased/Targeted Brain (Pro)Drug Delivery via Utilization of Solute Carriers (SLCs).
Pharmaceutics. Roč. 14, č. 6 (2022), č. článku 1234. E-ISSN 1999-4923
Institucionální podpora: RVO:61388963
Klíčová slova: blood-brain barrier (BBB) * brain drug delivery * prodrugs * solute carriers (SLCs)
Obor OECD: Biochemistry and molecular biology
Impakt faktor: 5.4, rok: 2022
Způsob publikování: Open access
https://doi.org/10.3390/pharmaceutics14061234

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.
Trvalý link: https://hdl.handle.net/11104/0332446