LRP-1 functionalized polymersomes enhance the efficacy of carnosine in experimental stroke

• Published in: Scientific reports Vol. 10; no. 1; p. 699
• Main Authors: Kim, Eun-Sun, Kim, Donghyun, Nyberg, Sophie, Poma, Alessandro, Cecchin, Denis, Jain, Saurabh A., Kim, Kyeong-A, Shin, Young-Jun, Kim, Eun-Hye, Kim, Minyeong, Baek, Seung-Hoon, Kim, Jin-Ki, Doeppner, Thorsten R., Ali, Ali, Redgrave, Jessica, Battaglia, Giuseppe, Majid, Arshad, Bae, Ok-Nam
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 20.01.2020; Nature Publishing Group
• Subjects: 14/28; 631/378/340; 64/60; 692/617/375/534; Animals; Brain Chemistry; Brain damage; Brain Ischemia - drug therapy; Carnosine; Carnosine - administration & dosage; Carnosine - chemistry; Carnosine - pharmacokinetics; Disease Models, Animal; Drug Carriers - chemistry; Drug Compounding; Drug dosages; Humanities and Social Sciences; Hydration; Ischemia; Low Density Lipoprotein Receptor-Related Protein-1 - metabolism; Male; Mice; Morphology; multidisciplinary; Neuroimaging; Neuroprotection; Peptides - chemistry; Peptides - metabolism; Pharmaceutical sciences; Pharmacy; Rats; Science; Science (multidisciplinary); Stroke; Stroke - drug therapy; Time Factors; Transmission electron microscopy; Treatment Outcome
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-57685-5

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.