Delivery of local anaesthetics by a self-assembled supramolecular system mimicking their interactions with a sodium channel.
Delivery of local anaesthetics by a self-assembled supramolecular system mimicking their interactions with a sodium channel.
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DOI：
10.1038/s41551-021-00793-y
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发表时间：
2021-09
影响因子：
28.1
通讯作者：
Kohane DS
中科院分区：
文献类型：
--
作者：
Ji T;Li Y;Deng X;Rwei AY;Offen A;Hall S;Zhang W;Zhao C;Mehta M;Kohane DS
位点1钠通道阻滞剂（S1SCB）作为有效的局部麻醉剂，但它们可引起严重的全身毒性。递送系统可用于降低毒性，但S1SCB的亲水性使其封装具有挑战性。在这里，我们报告了一个自组装的S1SCBs的传输系统，其设计灵感来自于S1SCBs与钠通道上的两个肽序列的特异性相互作用。具体而言，用疏水结构域修饰肽，使得它们可以组装成促进与S1SCBs河豚毒素、石房蛤毒素和二氨基甲酰基石房蛤毒素特异性结合的纳米纤维。在大鼠坐骨神经注射携带S1SCB的纳米纤维导致神经阻滞延长，全身毒性降低，局部组织反应良性。通过超分子相互作用模拟分子结合位点的策略可能更广泛地适用于受体介导药物的药物递送系统的设计。
Site-1 sodium channel blockers (S1SCBs) act as potent local anaesthetics, but they can cause severe systemic toxicity. Delivery systems can be used to reduce the toxicity, but the hydrophilicity of S1SCBs makes their encapsulation challenging. Here, we report a self-assembling delivery system for S1SCBs whose design is inspired by the specific interactions of S1SCBs with two peptide sequences on the sodium channel. Specifically, the peptides were modified with hydrophobic domains so that they could assemble into nanofibres that facilitated specific binding with the S1SCBs tetrodotoxin, saxitoxin and dicarbamoyl saxitoxin. Injection of S1SCB-carrying nanofibres at the sciatic nerves of rats led to prolonged nerve blockade and to reduced systemic toxicity, with benign local-tissue reaction. The strategy of mimicking a molecular binding site via supramolecular interactions may be applicable more broadly to the design of drug delivery systems for receptor-mediated drugs.
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影响因子：
4.9
作者：
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DOI：
10.7883/yoken1952.50.133
发表时间：
1997-06-01
期刊：
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影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
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