New prodrug approach enhances drug delivery to brain cells

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A new study from the University of Eastern Finland shows that drug delivery to the brain, and especially to glial cells, can be temporarily enhanced by products that include thyroxine or thyroxine-like molecules. The transporter protein OATP1C1, which is found in the brain, can be used to deliver such products. Results are published Journal of Medicinal Chemistry.

For the first time, researchers have used organic anion-transporting polypeptide 1C1 (OATP1C1) to enhance drug delivery to the brain. In the study, the products were used to transport anti-inflammatory drugs into the brain, where they were efficiently delivered to glial cells. Glial cells are known to be activated in many brain diseases to produce mediators that support neurons and maintain inflammation. Therefore, to have an effect on chronic inflammation in the brain, it is crucial to deliver anti-inflammatory drugs to the right cell types. The concept is even completely new worldwide.

Researchers at the University of Eastern Finland School of Pharmacy have long been trying to enhance brain drug delivery using L-type amino acid transporter 1, ie, the LAT1 protein and products that use it, amino acid derivatives. However, the OATP1C1 transporter protein used in the new study proved to be much more efficient at transporting thyroxine derivatives than LAT1.

The research employed computational molecular modeling to create protein models that were used to design and synthesize new products.

Drug transport systems are surprisingly poorly understood


A surprising observation from our study was that increasing the molecular size of drugs enhances their delivery to the brain and glial cells. Until now, it has been thought that a large molecular size is not exactly conducive to brain drug delivery.”


Kristina Hutunen, Research Group Director, Associate Professor, University of Eastern Finland


“This study highlights how poorly we still understand the mechanism of drug transport in our system. It is also a big reason why many new drugs, especially those intended to affect the central nervous system, unfortunately do not make it to market. The more we know. “This transport systems, we can take their effects into account when influencing the distribution of drugs in our body. It should also be considered early in drug development.”

The study forms part of a research project funded by the Research Council of Finland.


Journal Reference:

Tonduru, AK, etc. (2023). Targeting of glial cells by organic anion-transporting polypeptide 1C1 (OATP1C1)-using l-thyroxine-derived products. Journal of Medicinal Chemistry.

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