title: Angiopep-conjugated electro-responsive hydrogel nanoparticles: therapeutic potential for epilepsy.
abstract: A safe and effective therapy for epilepsy requires a drug delivery system that can penetrate the blood-brain barrier and subsequently release antiepileptic drugs rapidly to suppress neuronal discharges in a timely manner. We have developed electro-responsive hydrogel nanoparticles (ERHNPs) modified with angiopep-2 (ANG) to facilitate the delivery of the antiepileptic drug phenytoin sodium. The resulting ANG-ERHNPs had an average diameter of (102.3±16.8) nm and were electro-sensitive with regard to particle size and drug release in vitro. ANG-ERHNPs have the characteristics of penetrate the BBB easily, resulting in a higher distribution in the central system. The improved antiepileptic effects were investigated with the amygdala kindling model. The results demonstrate that the ANG-ERHNPs were able to transport antiepileptic drugs into the brain and release them under electroencephalograph epileptiform abnormalities to greatly improve the therapeutic index of existing drugs in clinical use.
authors.affiliation: Department of Pharmacology, Neurobiology of the Ministry of Health of China and Zhejiang Province Key Laboratory of Neurobiology, College of Pharmaceutical Sciences, School of Medicine, Zhejiang University, Hangzhou (China); Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058 (China).
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Ying
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Jiao
authors.initials: J
authors.lastname: Liang
authors.forename: Jiaxing
authors.initials: J
authors.lastname: Yue
authors.forename: Cenglin
authors.initials: C
authors.lastname: Xu
authors.forename: Lina
authors.initials: L
authors.lastname: Lu
authors.forename: Zhenghao
authors.initials: Z
authors.lastname: Xu
authors.forename: Jianqing
authors.initials: J
authors.lastname: Gao
authors.forename: Yongzhong
authors.initials: Y
authors.lastname: Du
authors.forename: Zhong
authors.initials: Z
authors.lastname: Chen
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000503:physiopathology; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001812:Blood-Brain Barrier / Q000378:metabolism; D002460:Cell Line; D016503:Drug Delivery Systems; D004560:Electricity; D004827:Epilepsy / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D010672:Phenytoin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: C531860:Angiopep-2; D000927:Anticonvulsants; D010455:Peptides; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D010672:Phenytoin
keywords: blood-brain barrier; drug delivery; epilepsy; hydrogels; nanoparticles