{"id":124,"date":"2020-05-13T13:55:17","date_gmt":"2020-05-13T10:55:17","guid":{"rendered":"https:\/\/sites.uef.fi\/drug-targeting\/?page_id=124"},"modified":"2026-07-03T09:15:39","modified_gmt":"2026-07-03T06:15:39","slug":"intra-brain-targeting","status":"publish","type":"page","link":"https:\/\/sites.uef.fi\/drug-targeting\/projects\/intra-brain-targeting\/","title":{"rendered":"Brain and Intra-Brain Targeting"},"content":{"rendered":"\n

Membrane transporters of the Solute Carrier (SLC) family are highly expressed in the brain and offer unique opportunities for targeted drug delivery. Transporters such as L-type Amino Acid Transporter 1 (LAT1), Organic Anion Transporting Polypeptides (OATPs), Monocarboxylate Transporters (MCTs), Organic Cation Transporters (OCTs), and Organic Anion Transporters (OATs) are expressed at the blood\u2013brain barrier (BBB) as well as in specific brain cell populations, including neurons, astrocytes, and microglia. These transport systems can therefore be exploited to deliver therapeutic agents not only into the brain but also selectively to distinct cell types within the central nervous system.<\/p>\n\n\n\n

Our research focuses on two complementary objectives:<\/p>\n\n\n\n

1. BBB-targeted drug delivery<\/h5>\n\n\n\n

Developing transporter-utilizing drugs and prodrugs that efficiently cross the blood\u2013brain barrier and enhance the brain delivery of neuroprotective and disease-modifying therapeutics<\/p>\n\n\n\n

2 . Cell-selective targeting within the brain<\/h5>\n\n\n\n

Harnessing transporter expression differences between brain cell populations to achieve selective delivery to neurons, astrocytes, microglia, and activated immune cells.<\/p>\n\n\n\n

By improving drug accumulation at the desired site of action, these strategies have the potential to increase therapeutic efficacy while reducing off-target exposure and adverse effects. Ultimately, our goal is to enable more precise treatments for central nervous system disorders in which neuroinflammation plays a key role, including Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, stroke, and acute brain infections.<\/em><\/p>\n\n\n\n

\"\"<\/figure>\n\n\n\n

Selected Publications<\/strong><\/h2>\n\n\n\n

Utilization of LAT1 as a carrier to Target (Pro)drugs into the Brain<\/u><\/strong><\/p>\n\n\n\n

Anamea, L.; Kr\u00e1lov\u00e1, A.; Tampio, J.; Shakirzyanova, A.; H\u00e4nninen, M.; Giniatullin, R.; Jalkanen, A.J.; Malm, T.; Lahtela-Kakkonen, M.; Huttunen K. M. Brain-targeted Jedi1 and Jedi2 derivatives as potent enhancers of Piezo1 ion channel activity. European Journal of Medicinal Chemistry<\/strong><\/em>, 2026<\/strong>, 302<\/em>, 118359. https:\/\/doi.org\/10.1016\/j.ejmech.2025.118359<\/a><\/p>\n\n\n\n

Kr\u00e1lov\u00e1, A.; Montaser, A. B.; Tampio, J.; Adla, S. K.; Jalkanen, A.; Rys\u00e4, J.; Huttunen, K. M. <\/strong>A novel paracetamol derivative alleviates lipopolysaccharide-induced neuroinflammation. European Journal of Pharmacology<\/em><\/strong>, 2025<\/strong>, 15<\/em>, 995, 177409. https:\/\/doi.org\/10.1016\/j.ejphar.2025.177409<\/a><\/p>\n\n\n\n

Hugele, A.; L\u00f6ffler, S.; Molina, B. H.; Guillon, M.; Montaser, A. B.; Auriola, S.; Huttunen, K. M.<\/strong> Aminopeptidase B Can Bioconvert L-Type Amino Acid Transporter 1 (LAT1)-Utilizing Amide Prodrugs in the Brain. Frontiers in Pharmacology<\/em><\/strong>, 2022<\/strong>, 13<\/em>, 1034964. https:\/\/doi.org\/10.3389\/fphar.2022.1034964<\/a><\/p>\n\n\n\n

Montaser, A. B.; Kuiri, J.; Natunen, T.; Hru\u0161ka, P.; Pot\u011b\u0161il, D.; Auriola, S.; Hiltunen, M.; Terasaki, T.; Lehtonen, M.; Jalkanen, A.; Huttunen, K. M.<\/strong> Enhanced drug delivery by a prodrug approach effectively relieves neuroinflammation in mice. Life Sciences<\/em><\/strong>, 2022<\/strong>, 310<\/em>, 121088. https:\/\/doi.org\/10.1016\/j.lfs.2022.121088<\/a><\/p>\n\n\n\n

Tampio, J.; L\u00f6ffler, S.; Guillon, M.; Hugele, A.; Huttunen, J.; Huttunen, K. M. Improved l-Type amino acid transporter 1 (LAT1)-mediated delivery of anti-inflammatory drugs into astrocytes and microglia with reduced prostaglandin production. International Journal of Pharmaceutics<\/em><\/strong>, 2021<\/strong>, 601<\/em>: 120565. https:\/\/doi.org\/10.1016\/j.ijpharm.2021.120565<\/a><\/p>\n\n\n\n

Montaser, A.; J\u00e4rvinen, J.; Loeffler, S.; Huttunen, J.; Auriola, S.; Lehtonen, M.; Jalkanen, A. J.; Huttunen, K. M. L-type amino acid transporter 1 enables the efficient brain delivery of small-sized prodrug across the blood-brain barrier and into human and mouse brain parenchymal cells. ACS Chemical Neuroscience<\/strong><\/em>, 2020<\/strong>, 11<\/em>(24): 4301-4315. https:\/\/doi.org\/10.1021\/acschemneuro.0c00564<\/a><\/p>\n\n\n\n

Tampio, J.; Huttunen J.; Montaser, A.; Huttunen, K. M. Targeting of Perforin Inhibitor into the Brain Parenchyma via Prodrug Approach Can Decrease Oxidative Stress and Neuroinflammation, and Improve Cell Survival. Molecular Neurobiology<\/em><\/strong>, 2020<\/strong>, 57<\/em>(11), 4563-4577. https:\/\/doi.org\/10.1007\/s12035-020-02045-7<\/a><\/p>\n\n\n\n

Montaser, A.; Lehtonen, M.; Gynther, M.; Huttunen, K. M. L-type amino acid transporter L-utilizing prodrugs of ketoprofen can efficiently reduce brain prostaglandin levels. Pharmaceutics<\/em><\/strong>, 2020<\/strong>, 12(4): E334 (1-12). https:\/\/doi.org\/10.3390\/pharmaceutics12040344<\/a><\/p>\n\n\n\n

Montaser, A.; Huttunen J.; Ibrahim, S. A; Huttunen, K. M. Astrocyte-Targeted Transporter-Utilizing Derivatives of Ferulic Acid Can Have Multifunctional Effects Ameliorating Inflammation and Oxidative Stress in the Brain. Oxidative Medicine and Cellular Longevity<\/em><\/strong>, 2019<\/strong>, 3528148<\/em>, 1-13. http:\/\/doi.org\/10.1155\/2019\/3528148<\/a><\/p>\n\n\n\n

Huttunen, J.; Peltokangas, S.; Gynther, M.; Natunen, T.; Hiltunen, M.; Auriola, S.; Ruponen, M.; Vellonen, K.-S.; Huttunen, K. M. L-Type Amino Acid Transporter 1 (LAT1\/Lat1)- Utilizing Prodrugs Can Improve the Delivery of Drugs into Neurons, Astrocytes and Microglia. Scientific Reports<\/em><\/strong>, 2019<\/strong>, 9 <\/em>(1): 12860-12872. http:\/\/doi.org\/10.1038\/s41598-019-49009-z<\/a><\/p>\n\n\n\n

Puris E, Gynther M, de Lange ECM, Auriola S, Hammarlund-Udenaes M, Huttunen KM, Loryan I. Mechanistic Study on the Use of the l-Type Amino Acid Transporter 1 for Brain Intracellular Delivery of Ketoprofen via Prodrug: A Novel Approach Supporting the Development of Prodrugs for Intracellular Targets. Molecular Pharmaceutics<\/em><\/strong>, 2019<\/strong>, 16 <\/em>(7), 3261-3274. http:\/\/doi.org\/10.1021\/acs.molpharmaceut.9b00502<\/a><\/p>\n\n\n\n

Puris E, Gynther M, Huttunen J, Auriola S, Huttunen KM. L-type amino acid transporter 1 utilizing prodrugs of ferulic acid revealed structural features supporting the design of prodrugs for brain delivery. European Journal of Pharmaceutical Sciences<\/em><\/strong>, 2019<\/strong>, 129<\/em>, 99-109. http:\/\/doi.org\/10.1016\/j.ejps.2019.01.002<\/a><\/p>\n\n\n\n

Gynther M, Puris E, Peltokangas S, Auriola S, Kanninen KM, Koistinaho J, Huttunen KM, Ruponen M, Vellonen KS. Alzheimer’s Disease Phenotype or Inflammatory Insult Does Not Alter Function of L-Type Amino Acid Transporter 1 in Mouse Blood-Brain Barrier and Primary Astrocytes. Pharmaceutical Research<\/em><\/strong>, 2018<\/strong>, 36 <\/em>(1), 1-17. doi.org\/10.1007\/s11095-018-2546-7<\/a><\/p>\n\n\n\n

Huttunen K. M. Identification of Human, Rat and Mouse Hydrolyzing Enzymes Bioconverting Amino Acid Ester Prodrug of Ketoprofen. Bioorganic Chemistry<\/em><\/strong>, 2018<\/strong>, 81<\/em>, 494-503. https:\/\/doi.org\/10.1016\/j.bioorg.2018.09.018<\/a><\/p>\n\n\n\n

Puris, E.; Gynther, M.; Huttunen, J.; Petsalo, A.; Huttunen, K. M. L-Type Amino Acid Transporter 1 Utilizing Prodrugs: How to Achieve Effective Brain Delivery and Low Systemic Exposure of Drugs. Journal of Controlled Release<\/em><\/strong>, 2017<\/strong>, 261<\/em>, 93-104. https:\/\/doi.org\/10.1016\/j.jconrel.2017.06.023<\/a><\/p>\n\n\n\n

Gynther, M.; Pickering, D. S.; Spicer, J. A.; Denny, W. A.; Huttunen, K. M. Systemic and Brain Pharmacokinetics of Perforin Inhibitor Prodrugs. Molecular Pharmaceutics<\/em><\/strong>, 2016<\/strong>, 13<\/em> (7): 2484-2491. http:\/\/dx.doi.org\/10.1021\/acs.molpharmaceut.6b00217<\/a><\/p>\n\n\n\n

Gynther, M.; Peura, L.; Vernerov\u00e1, M.; Lepp\u00e4nen, J.; Lehtonen, M.; Rautio, J.; Huttunen, K. M. Improved Pharmacokinetics of Valproic Acid by Amino Acid Prodrugs. Neurochemical Research<\/strong><\/em>, 2016<\/strong>, 41<\/em> (10), 2797-2809. http:\/\/dx.doi.org\/10.1007\/s11064-016-1996-8<\/a><\/p>\n\n\n\n

Peura, L.; Malmioja, K.; Huttunen, K. M.; Lepp\u00e4nen, J.; H\u00e4m\u00e4l\u00e4inen, M.; Forsberg, M. M.; Rautio, J.; Laine, K. Design, Synthesis and Brain Uptake of LAT1-Targeted Amino Acid Prodrugs of Dopamine. Pharmaceutical Research<\/em><\/strong>, 2013<\/strong>, 30 <\/em>(10), 2523-2537. http:\/\/dx.doi.org\/10.1007\/s11095-012-0966-3<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

Membrane transporters of the Solute Carrier (SLC) family are highly expressed in the brain and offer unique opportunities for targeted drug delivery. Transporters such as L-type Amino Acid Transporter 1 (LAT1), Organic Anion Transporting Polypeptides (OATPs), Monocarboxylate Transporters (MCTs), Organic Cation Transporters (OCTs), and Organic Anion Transporters (OATs) are expressed at the blood\u2013brain barrier (BBB) […]<\/p>\n","protected":false},"author":140,"featured_media":0,"parent":43,"menu_order":1,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_acf_changed":false,"_monsterinsights_skip_tracking":false,"_monsterinsights_sitenote_active":false,"_monsterinsights_sitenote_note":"","_monsterinsights_sitenote_category":0,"footnotes":""},"class_list":["post-124","page","type-page","status-publish","hentry"],"acf":[],"yoast_head":"\nBrain and Intra-Brain Targeting - Transporter Targeted Drug Delivery<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/sites.uef.fi\/drug-targeting\/projects\/intra-brain-targeting\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Brain and Intra-Brain Targeting - Transporter Targeted Drug Delivery\" \/>\n<meta property=\"og:description\" content=\"Membrane transporters of the Solute Carrier (SLC) family are highly expressed in the brain and offer unique opportunities for targeted drug delivery. 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