Molecular delivery targeting the cerebral microvasculature
Crossing the blood brain barrier (BBB) in drug delivery is one of the most challenging pharmacological missions. We tackled this problem and designed lipid-based nanocarriers loaded with radical-scavenging agents able to target the endothelia of the cerebral microvasculature and to protect brain tissue against oxidative stress.
In advanced age, blood-brain barrier (BBB) breakdown and neurovascular uncoupling can lead to cerebral blood flow deficits, neuroinflammation and reduced cognitive function. Those neurodegenerative diseases are frequently caused by age-related oxidative stress. A promising pharmacological strategy against reactive oxygen species (ROS) is the application of radical scavenging agents, e.g. artificial or natural polyphenols. Due to their high reactivity and low stability, such drugs have to be protected before reaching their target organs. Therefore, the application of protecting carrier particles is essential for a successful treatment.
In cooperation with Reynold´s Oklahoma Center on Aging (ROCA, Oklahoma City, USA), we have developed a polyphenol-containing lipid-based molecular delivery system that can effectively target cerebromicrovascular endothelial cells both in vitro and in vivo, attenuating age-related oxidative stress and improving neurovascular coupling. Especially aged organisms benefit from the anti-oxidative effect of those drugs as shown by their significantly improved neurovascular coupling responses by increasing nitric-oxide-mediated vasodilation.
1. Wiedenhoeft, Tarantini, Nyúl-Tóth, Yabluchanskiy, Csipo, Balasubramanian, Lipecz, Kiss, Csiszár, Csiszar, Ungvari (2019) Fusogenic liposomes effectively deliver resveratrol to the cerebral microcirculation and improve endothelium-dependent neurovascular coupling responses in aged mice. Geroscience, 41(6): 711
2. Csiszár, Csiszar, Pinto, Gautam, Kleusch, Hoffmann, Tucsek, Toth, Sonntag, Ungvari (2015) Resveratrol encapsulated in novel fusogenic liposomes activates Nrf2 and attenuates oxidative stress in cerebromicrovascular endothelial cells from aged rates, J Gerontol A 70:303
3. Csiszár, Hersch, Dieluweit, Biehl, Merkel, and Hoffmann (2010) Novel Fusogenic Liposomes for Fluorescent Cell Labeling and Membrane Modification, Bioconjugate Chemistry21: 537-543
Dr. Agnes Csiszar
- Institute of Biological Information Processing (IBI)
- Mechanobiology (IBI-2)