Construction Of Brain-Targeting TGN-HBc/PHT Protein Nanoparticle For Epilepsy Treatment

Epilepsy is one of the most common central nervous system diseases,affecting 0.5%to 1%of the world's population,and the prevalence rate in China alone is as high as 7.0‰.Most people with epilepsy get effective treatment through surgery,but 30%of patients eventually escalate into refractory epilepsy,which affects their quality of life.As an anti-epileptic drug commonly used in clinical practice,phenytoin(PHT)has significant epileptic inhibition effects,but also has some insurmountable shortcomings,such as poor water solubility,difficulty in absorption,obvious side effects,etc.The most important is that due to many epilepsy patients need to regularly take phenytoin,so they develop resistance,leading to epilepsy drugs can't reach to the lesion areaOur research aimed to construct a nanocarrier for targeted delivery of the antiepileptic drug PHT.Hepatitis B virus core protein virus-like particle(HBc)is a novel nano drug carrier with excellent biocompatibility and biodegradable,and can be functionally modified by genetic engineering or chemical methods,compared to other inorganic nanocarriers or organic micelle nanocarriers.These unique advantages offered endless possibilities for their applications in the biomedical field.In some published papers,HBc VLP was widely used in anti-tumor related research.In this paper,based on HBc VLP,the brain targeting peptide TGN was added to the particle surface designed by genetic engineering.The sulfonated ?-cyclodextrin was used to increase the water solubility of PHT,then it was loaded into HBc VLP by electrostatic action.Later,the application of materials in overcoming the blood-brain barrier,brain targeting and treatment of epilepsy were explored.The experimental results showed that TGN-HBc/PHT had excellent brain targeting performance and significant anti-epileptic effect,and could improve the resistance problem to some extent.In addition,in order to explore the biological toxicity of TGN-HBc VLP to humans,we directed differentiation of human 3D brains and obtained neuronal cells.MTT results showed that even materials with concentrations up to 300?g/ml were not significantly toxic to cells.The results of infiltration experiments of 3D brains showed that TGN-HBc VLPs could reach the central part of the brain with a diameter of 1 mm within 4 h,which proved that TGN-HBc VLP has good cell penetrating ability.Therefore,TGN-HBc VLP has great potential in the field of drug delivery for diseases related to nervous system.