Today, neurodegenerative diseases are affecting more and more individuals. A typical therapeutic target to treat the progression of the symptoms related to these diseases is the proinflammatory microglia. Diapocynin, the dimeric version of apocynin, is often the drug of choice. However, suitable carriers for its controlled delivery are currently lacking in the clinics. In fact, its high hydrophilicity hampers the development of a formulation enabling its sustained release in a biological environment. In this work, the possibility of modifying diapocynin is explored in order to synthesize a prodrug that can be chemically incorporated into biodegradable zwitterionic polymer nanoparticles (NPs). These NPs are synthesized via combination of ring opening polymerization and reversible addition–fragmentation chain transfer (RAFT) polymerization, allowing the incorporation of the desired number of diapocynin units into the carrier and thus to set the drug dosage a priori. The chemical binding of diapocynin avoids its premature release compared to its physical loading inside similar nanovectors. With this strategy, sustained diapocynin release can be achieved for more than 9 days, thus paving the way to a therapy with low number of repeated administrations.

中文翻译：

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用于从两性离子可生物降解纳米颗粒中延长释放的二夹竹桃麻素前药的合成

今天，神经退行性疾病正在影响越来越多的人。治疗与这些疾病相关的症状进展的典型治疗靶点是促炎性小胶质细胞。夹竹桃麻素的二聚体形式二夹竹桃麻素通常是首选药物。然而，目前临床上缺乏用于其控制递送的合适载体。事实上，其高亲水性阻碍了能够在生物环境中持续释放的制剂的开发。在这项工作中，探索了修饰二夹竹桃麻素的可能性，以合成一种前药，该前药可以化学结合到可生物降解的两性离子聚合物纳米粒子 (NPs) 中。这些NPs是通过开环聚合和可逆加成-断裂链转移（RAFT）聚合的组合合成的，允许将所需数量的二夹竹桃麻素单位掺入载体中，从而预先设定药物剂量。与类似纳米载体内的物理负载相比，二夹竹桃素的化学结合避免了其过早释放。通过这种策略，可以实现 9 天以上的持续释放二夹竹桃麻素，从而为重复给药次数少的疗法铺平道路。