Drug delivery in the body is a true pharmacological challenge, especially when treating diseases of the central nervous system. Many molecules are metabolized and quickly eliminated. Furthermore, they diffuse poorly through the blood-brain barrier that isolates the brain and spinal cord from the general circulation. Adenosine, a neurocompetent compound that acts on several receptors of the central and peripheral nervous systems, is one of them. It has never been used in the treatment of cerebral pathologies, due to its very short half-life after its administration in the blood (less than one minute), its potential side effects, and its inability to diffuse across the blood-brain barrier.
The Institut Galien, Hacettepe University (Turkey), and the CEA-IBITECS have performed and tested the vectorization of adenosine with squalene, a natural and biocompatible lipid. This assembly, in the form of 120-nm nanoparticles, was tested in murine models of cerebral ischemia and spinal cord trauma. The path of nanoparticles was followed in the bloodstream using a radioactive labeling that was performed at the CEA-IBITECS. The circulation time of the nanoparticles in the blood before their metabolization was extended relative to the administration of adenosine by itself. In addition, the researchers observed a greater interaction with the neurovascular elements to be treated. The neuroprotective effect was thereby dramatically enhanced. Moreover, no toxic hematological, cardiovascular or hepatic effects were found; the tests did not reveal any side effects on the sleep cycle or the level of food intake, either.
This discovery opens new therapeutic perspectives in the neurosciences. The functionalization of rapidly metabolized active molecules by squalene will help extend their time spent in the body, as well as the targeting of poorly accessible areas.
Observation of the nano-drug (in green) in the cytoplasm of cells. The cell nucleus is shown in blue, while the cell membrane is in red. © Nature Nanotechnology