Description
the prevention and treatment of neurodegenerative diseases and stroke-related brain damage are major and unresolved problems of contemporary medicine. One of the major limitations to current neurodegenerative disease treatment is an inefficient delivery of neuroprotective drugs to the affected part of the brain. The main project objective is to develop the new strategy of delivery of neuroprotective drugs by the nanocarriers, which are able to cross the blood-brain barrier without imposing side effect on its normal function. The ultimate project outcome will be novel drug delivery systems as candidates for future therapies of stroke and neurodegenerative diseases as Alzheimer’s and Parkinson’s or schizophrenia. The project output is the development of methodologies of encapsulation of neuroprotective drug, adjusted to their physicochemical properties, by formation of nanocarriers with the size in the range 10 – 150 nm is considered. The final target groups are hospitals and patients suffering from neurodegenerative diseases and stroke-related brain damage. Norwegian partners will provide expertise in methods of nanocarriers synthesis and drug efficiency in-vitro and in-vivo testing. The project will advance encapsulation technology by opening new fields of scientific collaboration between Polish and Norwegian partners and strengthening of existing ones.
Summary of project results
A successful prevention and an effective treatment of the central nervous system disorders such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis represent a major challenge of contemporary medicine. Consequently, much emphasis has been placed on the search for drugs for patients suffering from neurodegenerative processes. Unfortunately, despite the progress in the development of new neuroprotective substances, their effectiveness is still very limited, mainly due to their poor solubility and stability and unfavorable pharmacological properties leading to their deficient absorption and distribution. Those occur because numerous potential neuroprotectants do not penetrate the blood-brain-barrier (BBB). Nanotechnology provides novel strategies to overcome these limitations. Colloidal drug delivery systems (nanocapsules, nanocontainers, etc.) can challenge undesirable properties of the drugs due to their unique physicochemical and pharmacological properties. These novel strategies show promise for the effective prevention and treatment of the central nervous system disorders. In the project a consortium of Polish and Norwegian researchers concentrated their efforts on developing various methodologies of encapsulation of neuroprotectants to form nanocarriers with the size in the range 10 – 150 nm that could be delivered to brain. As the result of the project four novel encapsulation methodologies were developed to enclose hydrophobic as hydrophilic neuroprotective drugs. Size of nanocontainers was between 10 – 150 nm and they surfaces were modified for effective delivery. Besides selected neuroprotective components, fluorescent dyes and gold nanoparticles were chemically attached to nanocarriers that allowed their visualisation in in-vitro and in-vivo experiments. The nanocontainers were non-toxic to the selected cell lines and were efficiently transferred through the model “Blood-Brain-Barrier” some of them even without specific targeting ligand. The selected neuroprotectants were tested in the free form and in nanoparticulate formulations for their efficiency for preventing cell damage induced by, e.g., hydrogen peroxide. The results indicated that the tested substances in the encapsulated form can have similar or even enhanced neuroprotective properties, while polydatin and clozapine being the most efficient agents in nanoformulations and the most promising candidates for further therapies of neurodegenerative diseases.
Summary of bilateral results
The project enabled the partners to establish and strengthen collaboration that resulted in achieving shared results and improved knowledge concerning methodology of encapsulation of neuroprotective drugs that could be tested on either in-vitro (Polish partners) or in-vivo (Norwegian) blood-brain-barrier models. The cooperation allowed access to the techniques and instrumentation available in partners’ labs and led to development of complementary techniques of formation and modification of nanocarriers as well as understanding of the mechanisms of their transfer through the barrier and their neuroprotective action. It also allowed PhD students participating in the project to work in the international milieu and present the results of their work at international conferences. The funding of the project contributed to the strengthening of bilateral relations between partners that will results in common publications and applications for future projects. Common participation in the project workshop organized with the frame of 2nd Central European Biomedical Congress „From emerging biochemical strategies to personalized medicine” contributed to the project visibility among European researchers.