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Dr. Zhong Chen/'s group published in Angewandte Chemie International Edition

Date Posted :2014-07-18    Source :系统管理员    Views :862

July 2014, a research group headed by Professor Chen Zhong at Institute of Pharmacology, College of pharmaceutical sciences, Zhejiang University has recently published a research paper “Angiopep-conjugated Electro-responsive Hydrogel Nanoparticles: Therapeutic Potential for Epilepsy” in the journal “Angewandte Chemie International Edition”. The article reported that Angiopep-conjugated Electro-responsive Hydrogel Nanoparticles greatly improve the therapeutic index of existing drugs in clinical.

Epilepsy is one of the most prevalent neurological disorders, affecting nearly 1% of the population. Epileptic seizure is a paroxysmal abnormality in the synchronization of the electrical activity in brain neurons, which reflect voltage fluctuations resulting from ionic current flows within the neurons of the brain, so constraining the paroxysmal abnormality in the synchronization of the electrical activity to the local site and further suppressing it in a timely manner are the key points for preventing epileptic seizures. For most patients, antiepileptic drugs (AEDs) are the mainstay of the management of epilepsy. However, the relatively narrow therapeutic window and low permeability across the blood brain barrier (BBB) of conventional AEDs, such as phenytoin sodium (PHT), result in intolerable side effects, drug resistance and further an inability to completely control the seizures.

In response to these thorny issues: we developed electro-responsive hydrogel nanoparticles, which are characterized by stimuli-sensitive drug release upon external electrical fields and nano order size, were designed and further modified with brain targeting angiopep-2 peptide, a ligand of the low-density lipoprotein receptor-relatedprotein (LPR), for better targeting central neural system and anti-epileptic therapy. The in-vivo epilepsy model show they were able to transport the anti-epileptic drugs into brain and release the drug under electroencephalograph epileptiform abnormalities to greatly improve the therapeutic index of existing drugs in clinical.

Studying the mechanism of epileptogenesis and treatment is one of the important research directions for Professor Chen’s research group. This study is a cooperative outcome with Institute of Pharmaceutical. Co-first authors of the article are Dr. Xiaoying Ying and Dr. Yi Wang. The study was funded by the National Natural Science Foundation of China and the Key Project of Zhejiang Provincial Natural Science Foundation.

The main results in the article are summarized as follow: