2. Academic Validation
  3. Nanocage encapsulation improves antiepileptic efficiency of phenytoin

Nanocage encapsulation improves antiepileptic efficiency of phenytoin

  • Biomaterials. 2020 May;240:119849. doi: 10.1016/j.biomaterials.2020.119849.
Jie Zhao 1,  Zesen Ye 2,  Jun Yang 3,  Qiang Zhang 1,  Wenjun Shan 1,  Xiumin Wang 4,  Zhanxiang Wang 5,  Shefang Ye 1,  Xi Zhou 1,  Zhicheng Shao 6,  Lei Ren 7
Affiliations

Affiliations

  • 1 Key Laboratory of Biomedical Engineering of Fujian Province University/Research Center of Biomedical Engineering of Xiamen, Department of Biomaterials, College of Materials, Xiamen University, Xiamen, 361005, PR China.
  • 2 Fujian Provincial Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, School of Medicine, Xiamen University, Xiamen, 361102, PR China; Department of Neurosurgery, the First Affiliated Hospital of Xiamen University, Xiamen, 361005, PR China.
  • 3 Department of Neurosurgery, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361102, PR China.
  • 4 School of Pharmaceutical Sciences, Xiamen University, Xiamen, 361102, PR China.
  • 5 Department of Neurosurgery, the First Affiliated Hospital of Xiamen University, Xiamen, 361005, PR China.
  • 6 Fujian Provincial Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, School of Medicine, Xiamen University, Xiamen, 361102, PR China. Electronic address: zcshao@xmu.edu.cn.
  • 7 Key Laboratory of Biomedical Engineering of Fujian Province University/Research Center of Biomedical Engineering of Xiamen, Department of Biomaterials, College of Materials, Xiamen University, Xiamen, 361005, PR China; State Key Lab of Physical Chemistry of Solid Surfaces, Xiamen University, Xiamen, 361005, PR China. Electronic address: renlei@xmu.edu.cn.
PMID: 32087458 DOI: 10.1016/j.biomaterials.2020.119849
Abstract

More than 30% of patients with epilepsy progress to drug-resistant epilepsy, leading to a significant increase in morbidity and mortality of epilepsy. The limitation of epileptic drug to reach the epileptogenic focus is the critical reason, and the blood-brain barrier (BBB) plays a crucial role. Here, we successfully constructed a hepatitis B core (HBc) protein nanocage (NC) with the insertion of brain target TGN peptide for facilitating epileptic drug phenytoin delivery to the brain. Our results demonstrated that this nanocage can specifically and efficiently target the brain tissue by 2.4 fold and increase the antiepileptic efficiency of phenytoin about 100 fold in pilocarpine induced models of epilepsy. Both in vivo mice and in vitro human neural three-dimensional cortical organoids demonstrated high penetration ability. These functions are achieved through the facilitation of brain target peptide TGN rather than disruption of brain blood barrier. In summary, we presented an efficient antiepileptic Drug Delivery nanocage for the treatment of refractory epilepsy. Moreover, this therapeutic modulation also provides promising strategy for other intractable Neurological Disease.

Keywords

Antiepileptic drug; Epilepsy; Human cortical organoids; Protein nanocage.

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