Improved l-Type amino acid transporter 1 (LAT1)-mediated delivery of anti-inflammatory drugs into astrocytes and microglia with reduced prostaglandin production

Janne Tampio,Susanne Löffler,Melina Guillon,Agathe Hugele,Johanna Huttunen,Kristiina M Huttunen

International Journal of Pharmaceutics（2021）

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摘要

•l-Type amino acid transporter 1 (LAT1) can deliver drugs into the brain parenchyma.•Non-steroidal anti-inflammatory drugs (NSAIDs) could inhibit neuroinflammation.•Novel LAT1-utilizing ester prodrugs of 4 NSAIDs was synthesized and evaluated.•Prodrugs were uptaken into microglia/astrocytes and inhibited PGE2 production.•Prodrugs were bioconverted by CES and other enzymes with varable rates.

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关键词

Astrocytes,l-type amino acid transporter 1 (LAT1),Microglia,non-steroidal anti-inflammatory drugs (NSAIDs),Prodrugs,prostaglandin E2 (PGE2)

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