Considering that currently used anti-epileptic drugs (AEDs) in clinical practice can only suppress abnormal discharges without intervening in inflammatory microenvironment, combining anti-inflammatory and antioxidant agents with AEDs is probably an effective approach to overcoming the limitations of AEDs. Additionally, damaged neurons and blood-brain barrier (BBB) in epileptic foci require corresponding repair to minimize risks of triggering new epileptogenic events. Unfortunately, there are hardly any effective strategies that integrate inflammatory microenvironment regulation with epileptogenic focus restoration. Therefore, based on the conductive polymer polypyrrole (ppy), we have designed a multiple-stimuli-responsive macrophage membrane-coated drug delivery system, co-loaded with inflammation-regulating drug fingolimod (FTY) and lesion-repairing drug citicoline sodium (CTC). This biomimetic system enables selective accumulation and release of drugs in epileptic foci, exerting broad effects on various cells and damage factors within lesions (Figure 1). By comprehensively managing various pathological events in epileptic lesions, it holds promise for fully regulating and repairing epileptic focus microenvironment.
Figure 1. Scheme of design concept and therapeutic strategy of biomimetic macrophage membrane-coated dual-drug-loaded ppy nanoparticles. [1] After being encapsulated by macrophage membrane, dual-drug-loaded nanoparticles can recognize and bind to epileptic focus BBB under inflammatory conditions, subsequently crossing the BBB to reach diseased brain parenchyma. [2] Dual-drug-loaded nanoparticles are capable of responding to extracellular ROS and abnormal bioelectrical stimuli to accelerate the release of FTY, while also releasing CTC in response to acidic lysosomal environment inside cells. [3] Nanoparticles release both drugs while simultaneously scavenging ROS at lesion sites, ultimately achieving multiple therapeutic effects, including protecting and repairing damaged neurons, stabilizing glial microenvironment, and restoring BBB integrity.
Related research (DOI: 10.1002/adfm.202510305) has been available online powered by Advanced Functional Materials. Zheng Zhou, a doctoral student, is the first author of the paper, and Professor Chen Jiang is the corresponding author. Please kindly refer to https://advanced.onlinelibrary.wiley.com/doi/10.1002/adfm.202510305 for more information.
