LRP-1 functionalized polymersomes enhance the efficacy of carnosine in experimental stroke
| Autor: | Eun Sun Kim, Minyeong Kim, Saurabh A. Jain, Young-Jun Shin, Ali Ali, Eun-Hye Kim, Sophie Nyberg, Arshad Majid, Alessandro Poma, Jessica Redgrave, Donghyun Kim, Giuseppe Battaglia, Jin-Ki Kim, Thorsten R. Doeppner, Denis Cecchin, Seung-Hoon Baek, Kyeong-A Kim, Ok-Nam Bae |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Time Factors Dependent manner Drug Compounding lcsh:Medicine Carnosine Pharmacology Molecular neuroscience Neuroprotection Article Brain Ischemia 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine medicine Animals lcsh:Science Receptor Stroke Brain Chemistry Drug Carriers Multidisciplinary business.industry lcsh:R medicine.disease Orders of magnitude (mass) 3. Good health Rats Disease Models Animal 030104 developmental biology Treatment Outcome chemistry Polymersome lcsh:Q business Peptides 030217 neurology & neurosurgery Preclinical imaging Low Density Lipoprotein Receptor-Related Protein-1 |
| Zdroj: | Scientific Reports Scientific Reports, Vol 10, Iss 1, Pp 1-8 (2020) |
| ISSN: | 2045-2322 |
| Popis: | Stroke is one of the commonest causes of death with limited treatment options. L-Carnosine has shown great promise as a neuroprotective agent in experimental stroke, but translation to the clinic is impeded by the large doses needed. We developed and evaluated the therapeutic potential of a novel delivery vehicle which encapsulated carnosine in lipoprotein receptor related protein-1 (LRP-1)-targeted functionalized polymersomes in experimental ischemic stroke. We found that following ischemic stroke, polymersomes encapsulating carnosine exhibited remarkable neuroprotective effects with a dose of carnosine 3 orders of magnitude lower than free carnosine. The LRP-1-targeted functionalization was essential for delivery of carnosine to the brain, as non-targeted carnosine polymersomes did not exhibit neuroprotection. Using Cy3 fluorescence in vivo imaging, we showed that unlike non-targeted carnosine polymersomes, LRP-1-targeted carriers accumulated in brain in a time dependent manner. Our findings suggest that these novel carriers have the ability to deliver neuroprotective cargo effectively to the brain. |
| Databáze: | OpenAIRE |
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