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Nanoengineered on-demand drug delivery system improves efficacy of pharmacotherapy for epilepsy.

ABSTRACT: Long-term pharmacotherapy, serving as the main therapeutic approach for epilepsy prophylaxis, has suffered from limited efficacy and potential side effects because of the blood-brain barrier (BBB) and untimely medication. Here, we reported a nanoengineered drug delivery system for synergistic brain-targeting delivery and on-demand drug release of antiepileptic drugs (AEDs). The dopamine-pyrrole hybrid system can improve delivery efficiency through a combination of receptor-mediated transcytosis and BBB disruption–enabled transport induced by photothermal conversion of near-infrared light. Incorporation of polydopamine endowed the delivery system with enhanced conductivity and sensitivity, giving sustained (2 hours) and rapid (30 s) drug release in response to epileptiform discharges. Acute, continuous, and spontaneous seizure models validated that the delivery system could inhibit seizures upon epileptiform abnormalities, treated by one-fifth of the conventional dosage. Complemented with satisfactory biosafety results, this “smart” modality is promising to be an effective and safe strategy to improve the therapeutic index of AEDs for epilepsy.

SUBMITTER: Wu D

PROVIDER: S-EPMC8754409 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Nanoengineered on-demand drug delivery system improves efficacy of pharmacotherapy for epilepsy.

Wu Di D Fei Fan F Zhang Qi Q Wang Xia X Gong Yiwei Y Chen Xiaojie X Zheng Yuyi Y Tan Bei B Xu Cenglin C Xie Hujun H Fang Wenjun W Chen Zhong Z Wang Yi Y

Science advances 20220112 2

Long-term pharmacotherapy, serving as the main therapeutic approach for epilepsy prophylaxis, has suffered from limited efficacy and potential side effects because of the blood-brain barrier (BBB) and untimely medication. Here, we reported a nanoengineered drug delivery system for synergistic brain-targeting delivery and on-demand drug release of antiepileptic drugs (AEDs). The dopamine-pyrrole hybrid system can improve delivery efficiency through a combination of receptor-mediated transcytosis ...[more]

PMID: 35020438

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Project description:Introduction: When using portable oxygen, a demand oxygen delivery system (DODS), which senses the beginning of inhalation and delivers a bolus of oxygen, is often used. However, conventional DODS may not supply sufficient oxygen when reduced tidal flow fails to trigger the flow sensor. Recently, "auto-DODS," which detects the negative pressure of inhalation and switches among 3 trigger sensitivity levels (standard, high, and extra high), has been developed to improve the efficacy of oxygenation. An auto-DODS can also supply pulsed-flow oxygen when it detects apnea, whereas a conventional DODS has only standard sensitivity. This randomized, open-label, crossover pilot study compared the performance of an auto-DODS with that of a conventional DODS.Methods: We recruited patients with chronic obstructive pulmonary disease (COPD) or interstitial pneumonia receiving long-term oxygen therapy. Interventions were performed on 2 different days for each participant. On each day, an auto-DODS or a conventional DODS were tested at rest for 30 minutes and during the 6-minute walk test. The primary outcome was mean oxygen saturation (SpO2). Secondary outcomes were the ratios of time for each sensitivity level and pulsed-flow oxygen when using the auto-DODS, total time desaturated below SpO2 90%, percentage of time desaturated below SpO2 90%, minimum SpO2, mean and maximum pulse rate, six-minute walk distance, recovery time after 6-minute walk test, modified Borg scale, comfort, and discomfort index.Results: When using the auto-DODS at rest, a high or extra high sensitivity level was observed in addition to standard sensitivity in 6 of 8 participants. During the 6-minute walk test, only standard sensitivity was observed in 6 participants. Mean SpO2 differences between the auto-DODS and conventional DODS at rest and during the 6-minute walk test were -0.6 [-4.5, 3.4] and 0.0 [-2.5, 2.5] ([95% confidence interval]), respectively, neither of which were significant (P = .73 and P = .99). There were no significant differences in secondary outcomes. There were no adverse events when using the auto-DODS.Conclusions: This study showed that the auto-DODS did not show superiority in oxygenation either at rest or during exercise compared to a conventional DODS. The auto-DODS was shown to supply oxygen safely and detect inhalations with various trigger sensitivities.

Dataset Information

Nanoengineered on-demand drug delivery system improves efficacy of pharmacotherapy for epilepsy.

Publications

Nanoengineered on-demand drug delivery system improves efficacy of pharmacotherapy for epilepsy.

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