Theranostic nanocarriers for drug delivery in central nervous system disorders

About this project

<p>Ischemic stroke is one of the major causes of death or long-term disabilities worldwide; thus, prevention and treatment of neurodegenerative diseases and stroke-related brain damage, being still largely unresolved problems of contemporary medicine, require new technologies for diagnostics and therapeutics. One of the major limitations to current neurodegenerative disease treatment is an inefficient delivery of neuroprotective drugs to the affected part of the brain due to the blood-brain barrier (BBB) that is permeable only by small, lipophilic molecules. Additionally, some of the orally delivered neuroprotective drugs may influence the whole organism, thus causing peripheral toxicity and numerous adverse reactions. Therefore, despite the progress in understanding molecular mechanisms of neuronal injury and preventing them, only few neuroprotective substances are used in the clinic and their efficiency in the treatment of stroke and neurodegenerations is still not satisfactory. The main project objective is to develop the new strategy of delivery of selected neuroprotectants by theranostic nanocarriers that can cross the blood-brain barrier without imposing side effects on its normal function. We will concentrate on developing methodology of encapsulation of neuroprotectants and fluorescent or MRI contrast agents in nanocarriers with the size below 150 nm and surfaces functionalized for targeted delivery. Immunosupressant drugs such as cyclosporine A (CsA) and FK506 are neuroprotective in animal models of brain ischemia. CsA inhibits the opening of the mitochondrial permeability transition pore, thereby maintaining mitochondrial homeostasis following brain ischemia by inhibiting calcium influx and preserving mitochondrial membrane potential. However, high systemic doses of these drugs result in undesired effects and toxicity.</p>

Bilateral cooperation results

Project was realized in collaboration between Polish and Norwegian istitutions as follow:  Polish partner (ICSC) was mainly involved in the development of multilayer nanocarriers containing oil-soluble neuroprotectants, Ederavone, Ebselen (EB), and carnosic acid (CA) and their synthesis was supported with the competence of Norwegian partner (SINTEF) concerning NMR analysis of PEG grafted polyelectrolytes;  SINTEF was responsible for synthesizing neuroprotective CeO2 nanoparticles and POSS-based contrast agents.  The synthesized nanoparticles were characterized by Polish partners: (i) biosafety and neuroprotection by Institute of Pharmacology) and (ii) MRI contrasting properties by the Institute of Nuclear Physics. The second Norwegian (OUH) partner provided their expertise in the fluorescence staining of nanocarriers, determination of fluorescent properties and the application of confocal microscopy for in-situ detection of nanocarriers. It is stated in the report, that the application for future funding will be realized when appropriate call is announced (ERA-NET, HORIZON EUROPE, NCN)

Project partners

• SINTEF AS Donor project partner· Norway
• Oslo University Hospital Donor project partner· Norway
• Maj Institute of Pharmacology Polish Academy of Sciences Project partner· Poland
• The Henryk Niewodniczański Institute of Nuclear Physics Polish Academy of Sciences Project partner· Poland