Apamin-mediated actively targeted drug delivery for treatment of spinal cord injury: more than just a concept.
Apamin-mediated actively targeted drug delivery for treatment of spinal cord injury: more than just a concept.
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DOI：
10.1021/mp500393m
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发表时间：
2014-08
影响因子：
4.9
通讯作者：
Jin Wu;Hong Jiang;Q. Bi;Qin Luo;Jianjun Li;Yan Zhang;Zhang-bao Chen;Chong Li
中科院分区：
文献类型：
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作者：
Jin Wu;Hong Jiang;Q. Bi;Qin Luo;Jianjun Li;Yan Zhang;Zhang-bao Chen;Chong Li
面对脊髓损伤（SCI）所带来的复杂医学挑战，并考虑到缺乏任何可用的治愈性疗法，开发一种递送现有药物或候选药物的新方法可以被认为与开发新的治疗分子一样重要。通过结合目前临床使用或正在测试的三种成分，我们设计了一种基于apamin修饰的聚合物胶束（APM）的中枢神经系统靶向给药系统。蜂毒蛋白是蜂毒的主要成分之一，作为靶向部分，聚乙二醇（PEG）二硬脂酰磷脂酰乙醇胺（DSPE）作为载药材料，姜黄素作为治疗剂。将Apamin与NHS（N-羟基琥珀酰亚胺）-PEG-DSPE以位点特异性方式偶联，并通过薄膜水合法制备APM。包含0.5mol%的具有50 nm粒径的靶向配体的制剂在体内显示出强靶向效率，并在药效学测定中进行了评价。通过每日静脉内施用低剂量APM（对应于5 mg/kg姜黄素）进行7天治疗。与假处理组相比，SCI小鼠模型中发现恢复显著增强，存活期延长，且无明显毒性。单剂量的apamin缀合的聚合物比LD 50量低约700倍，表明APM和apamin具有作为脊髓靶向配体用于递送治疗中枢神经系统疾病的药剂的临床应用潜力。
Faced with the complex medical challenge presented by spinal cord injuries (SCI) and considering the lack of any available curative therapy, the development of a novel method of delivering existing drugs or candidate agents can be perceived to be as important as the development of new therapeutic molecules. By combining three ingredients currently in clinical use or undergoing testing, we have designed a central nervous system targeted delivery system based on apamin-modified polymeric micelles (APM). Apamin, one of the major components of honey bee venom, serves as the targeting moiety, poly(ethylene glycol) (PEG) distearoylphosphatidylethanolamine (DSPE) serves as the drug-loaded material, and curcumin is used as the therapeutic agent. Apamin was conjugated with NHS (N-hydroxysuccinimide)-PEG-DSPE in a site-specific manner, and APM were prepared by a thin-film hydration method. A formulation comprising 0.5 mol % targeting ligand with 50 nm particle size showed strong targeting efficiency in vivo and was evaluated in pharmacodynamic assays. A 7-day treatment by daily intravenous administration of low doses of APM (corresponding to 5 mg/kg of curcumin) was performed. Significantly enhanced recovery and prolonged survival was found in the SCI mouse model, as compared to sham-treated groups, with no apparent toxicity. A single dose of apamin-conjugated polymers was about 700-fold lower than the LD50 amount, suggesting that APM and apamin have potential for clinical applications as spinal cord targeting ligand for delivery of agents in treatment of diseases of the central nervous system.