Science Advances Zhejiang University of Traditional Chinese Medicine Wang Yi/Chen Zhong develops new nano-drug delivery system, on-demand drug delivery system is expected to improve the effect of epilepsy treatment

As the main treatment method for epilepsy prevention, iNature long-term drug treatment has limited efficacy and potential side effects due to the untimely blood-brain barrier (BBB) ​​and drug treatment
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On January 12, 2022, a research paper titled "Nanoengineered on-demand drug delivery system improves efficacy of pharmacotherapy for epilepsy" was published online in Science Advances by Wang Yi and Chen Zhong from Zhejiang University of Traditional Chinese Medicine.
Nanoengineered drug delivery systems for synergistic targeted brain delivery and on-demand drug release of antiepileptic drugs (AEDs)
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The dopamine-pyrrole hybrid system can enhance delivery efficiency by combining receptor-mediated endocytosis and BBB-disrupting transport induced by photothermal conversion via near-infrared light
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The addition of polydopamine imparted enhanced conductivity and sensitivity to the delivery system, giving sustained (2 hours) and rapid (30 seconds) drug release during epileptiform discharges
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Acute, continuous, and spontaneous seizure models validate the delivery system to suppress seizures in epileptiform abnormalities at a therapeutic dose that is only one-fifth of the conventional dose
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Coupled with satisfactory biosafety results, this "smart" modality holds promise as an effective and safe strategy to improve the treatment of epilepsy AEDs
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In addition, on August 13, 2021, Wang Yi and Chen Zhong of Zhejiang University of Traditional Chinese Medicine jointly published a research paper entitled "Thermo-sensitive micelles extend therapeutic potential for febrile seizures" in Signal Transduction and Targeted Therapy.
The small-molecule caspase-1 inhibitor CZL80 was loaded into thermosensitive micelles to report a thermally responsive strategy for effective FS treatment, allowing drug release under local thermal stimulation, thereby extending the therapeutic window of FS
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In conclusion, CZL80-loaded micelles may be used as a potent and effective FS-producing agent for individuals at high risk for seizures with fever, such as younger individuals, those with low peak thresholds or short seizure latencies, and/or those with a family history of FS.
Safety precautions
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This may in the future shift the therapeutic paradigm of drug therapy to an on-demand "smart" control of FS (click to read)
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Epilepsy is a chronic brain disorder that affects approximately 1% of the world's population and is characterized by unprovoked and recurrent seizures
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Seizures are caused by abnormal, excessive and synchronized neuronal activity in the brain
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If measures are not taken in time to suppress the discharges, epileptic discharges from the initial focal area can rapidly spread throughout the brain
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Antiepileptic drugs (AEDs) are considered treatments to control seizures
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Due to the recurrent nature of epileptic seizures, long-term drug therapy is essential to maintain AED plasma concentrations within a stable therapeutic dose range
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However, traditional AED drugs, such as phenytoin (PHT), suffer from a narrow therapeutic window and insufficient blood-brain barrier (BBB)-induced brain targeting
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In addition, prolonged exposure of the central nervous system (CNS) to AEDs can lead to adverse effects (eg, cognitive impairment, psychiatric problems, and impaired liver and kidney function) and drug-resistant epilepsy
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These conditions are exacerbated by treatment regimens for status epilepticus (SE), which require patients to take regular AEDs for timely control of persistent and repetitive seizures
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Failure to control SE results in severe neurological sequelae and short-term mortality of 15% to 20%
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Therefore, it is imperative to improve the efficacy and reduce side effects of AED treatment
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An ideal epilepsy drug therapy requires (i) on-demand drug release to suppress epileptic discharge and (ii) efficient penetration of the BBB
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Over the past few decades, efforts have been devoted to developing smart drug delivery systems (DDS) in order to increase drug concentrations in the brain
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Various nanoparticle-based DDSs for AEDs, including polymer nanoparticles, hydrogels, and protein nanocages with high encapsulation efficiency, have shown their advantages over epilepsy control
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However, bottlenecks still exist, which largely impair the efficacy of current DDS treatments for epilepsy
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Considering the pathogenic characteristics of SE, sustained drug release in response to epileptic discharges is considered a reliable strategy for suppressing persistent seizures
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Characterization of Electrically Responsive DDS for Enhanced Epilepsy Treatment (Image courtesy of Science Advances) Another challenge for AED drugs is crossing the BBB, which acts as a protective half-membrane of the CNS
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To improve BBB crossing, several brain-targeting strategies, including receptor-mediated endocytosis and BBB disruption-enabled transport, have been developed for BBB penetration
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It is hypothesized that a combined strategy of receptor-mediated transcytosis and NIR could synergistically improve the efficiency of AED targeting to epileptogenic regions
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During an epileptic seizure, AEDs can be released in a timely and sustained manner in response to subsequent epileptic discharges
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However, it begs the question: how can these functional motifs be integrated into a usable DDS for epilepsy treatment? This study reports a nanoengineered drug delivery system for synergistic targeted brain delivery and on-demand drug release of antiepileptic drugs (AEDs)
.

The dopamine-pyrrole hybrid system can enhance delivery efficiency by combining receptor-mediated endocytosis and BBB-disrupting transport induced by photothermal conversion via near-infrared light
.

The addition of polydopamine imparted enhanced conductivity and sensitivity to the delivery system, giving sustained (2 hours) and rapid (30 seconds) drug release during epileptiform discharges
.

Acute, continuous, and spontaneous seizure models validate the delivery system to suppress seizures in epileptiform abnormalities at a therapeutic dose that is only one-fifth of the conventional dose
.

Coupled with satisfactory biosafety results, this "smart" modality holds promise as an effective and safe strategy to improve the treatment of epilepsy AEDs
.

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