Log In

G-2385

Development of the flavonoid-loaded magnetic nanoparticles for the epilepsy treatment in animal models of rats

Project Status: 3 Approved without Funding
Duration in months: 24 months

Objective

Concern for biosafety and biosecurity is the only right strategy for the development of a civilized world. Focusing both on ecology and human health, biosafety is the prevention of large-scale loss of biological integrity. Nowadays biosafety is becoming a global concern which require multilevel resources and international collaboration to monitor, prevent and correct accidents from unintended and malicious release and also to prevent usage of biological sample by bioterrorists to create biological weapons of mass destruction.

Despite the fact that today's efforts in the biosafety sector are very high, the probability of using biological weapons is still high. There is doubt that the Biological Weapons Convention is not enough to prohibit the bacterial (biological) and toxic weapon. Still there is a danger that biological arms could be used by terrorists. It is clear that modernization of this Agreement urgently requires. On the other hand the Biological Weapons Convention do not prohibit the work on defense facilities. One such possibility is to develop an effective treatment strategy that is easy to use, is non-invasive, relatively inexpensive and has no side effects.

As already mention above the basic essence of the biological war is for military purposes using of biological methods (bacteria, viruses, biotoxins, etc.) to challenge and distribute human, animal and plant diseases. Bacterial, viral, fungal infections in the brain and spinal cord can cause dangerous inflammation. Inflammation of the brain- encephalitis mostly are induced by viruses and affects approximately 7.5 people/100 000 and carries a high rate of morbidity and mortality. Arthropod-borne (arbo) viruses are the leading cause of viral encephalitis in the world today, with between 10% and 35% of patients infected with these viruses displaying some form of seizure. Several neurotropic DNA viruses, including Herpes and cytomegalovirus also commonly cause seizures in infected patients. Most patients with viral encephalitis will develop some form of seizure during the infectious process, and of those who survive encephalitic disease, approximately 4–20% will develop epilepsy (Getts et al., 2008).

Epilepsy is a chronic neurological disease, which affects approximately 1% of the world’s population. Epilepsy is usually controlled, but not cured with medication. However, more than 35% of epilepsy is drug-resistant. Temporal lobe epilepsy (TLE) is the one of the common human seizure disorder (Engel, 2006) characterized by seizures poorly controlled with anticonvulsant medications. Considering the importance of oxidative stress in epilepsy disorders in recent years the studies for the determination of new treatment strategy for epilepsy focuses on flavonoids – plants antioxidants, because of their ability to scavenge reactive oxygen species (ROS) and to inhibit pathological nitric oxide (NO). Although most of flavonoids have many pharmacological effects such as antioxidant, antiradical, anti-inflamatory, antimutagenic, anticarcinogenic, antiangiogenic, antibacterial, antiviral and antiaging, stimulating antioxidant enzymes in the human body (see Pool et al., 2012) they are rarely used in clinics because it contains many free phenolic hydroxyl groups, which may be easily oxidized in the air. In addition, it 200(Guan et al., 2017, Abraham & Acree, 2014). So poor bioavailability limits their biological effects in vivo. The modern approach to solve problem is usage of nanoparticles (NP). It is shown that nanoparticles protect, control the release and increase the action of bioactive compounds. Thus, it is important to develop the flavonoid-loaded magnetic nanoparticles for the treatment of epilepsy and to investigate the antiepileptic potency of controlled by magnetic field drug- delivery- system in animal models of TLE.

The aim of our project is to assess the effects stimulated by Flavonoids -loaded-magnetic-NPs (FMNP)s in animal models of Temporal Lobe Epilepsy (TLE). Flavonoids (Quercetin, Catechins) will be attached with the magnetic-nanoparticles and targeting-treatment of epilepsy with FMNP (Q/C-MNP) after their injection in the carotid artery will be controlled by the magnetic field. Usage of magnetic-targeted-drug-delivery-system to apply the flavonoids precisely to the epileptic areas is innovative and will be performed for the first time. Comparative analysis of the effects of Quercetin, Catechins alone and Q/C-MNP will be accomplished, and, the range of antiepileptic potency of Q/C- MNP will be defined. Targeting-treatment of epilepsy with Q/C-MNP by magnetic field will be noninvasive and will promote to develop new, cost efficient treatment strategy for the epilepsy.

Obtained data will facilitate the execution of flavonoids in the clinic as well as new recommendations on human consumption ration. The outcomes of the project are on the side of the clinicians and the pharmaceutical industry, as the plant origin substances which are prophylactic or have healing efficiencies are characterized by a wider use.

Participating Institutions

LEADING

I. Javakhishvili Tbilisi State University (TSU)

COLLABORATOR

Kyushu University

COLLABORATOR

University of Washington / Department of Bioengineering (BIOE)