Tailored delivery of analgesic ziconotide across a blood brain barrier model using viral nanocontainers.
Tailored delivery of analgesic ziconotide across a blood brain barrier model using viral nanocontainers.
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DOI：
10.1038/srep12497
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发表时间：
2015-08-03
影响因子：
4.6
通讯作者：
Holford M
中科院分区：
文献类型：
--
作者：
Anand P;O'Neil A;Lin E;Douglas T;Holford M
血脑屏障(BBB)往往是包括多肽、抗生素和化疗药物在内的大量候选药物难以逾越的障碍。设计一种巧妙的跨血脑屏障的给药方法对于解锁多肽疗法的广泛应用至关重要。本文介绍了一种用于通过血脑屏障运送多肽药物的工程纳米容器，该容器封装了止痛海洋蜗牛多肽(Prialt®)。我们开发了一种基于鼠伤寒沙门氏菌P22噬菌体衣壳的双功能病毒纳米容器，在衣壳的内腔中遗传地掺入齐康肽，并在衣壳的外部化学附着穿透HIV-TAT肽的细胞。通过一种可循环的非细胞毒性内皮细胞途径，成功地在大鼠和人脑微血管内皮细胞(BMVEC)的血脑屏障模型中转运了含有zicone的P22病毒样颗粒(VLP)。这项工作证明了使用可调节的VLP药物输送纳米容器穿过血脑屏障，开发一种可能的替代鞘内注射齐康肽的方法的原则证据。
The blood brain barrier (BBB) is often an insurmountable obstacle for a large number of candidate drugs, including peptides, antibiotics, and chemotherapeutic agents. Devising an adroit delivery method to cross the BBB is essential to unlocking widespread application of peptide therapeutics. Presented here is an engineered nanocontainer for delivering peptidic drugs across the BBB encapsulating the analgesic marine snail peptide ziconotide (Prialt®). We developed a bi-functional viral nanocontainer based on the Salmonella typhimurium bacteriophage P22 capsid, genetically incorporating ziconotide in the interior cavity, and chemically attaching cell penetrating HIV-Tat peptide on the exterior of the capsid. Virus like particles (VLPs) of P22 containing ziconotide were successfully transported in several BBB models of rat and human brain microvascular endothelial cells (BMVEC) using a recyclable noncytotoxic endocytic pathway. This work demonstrates proof in principle for developing a possible alternative to intrathecal injection of ziconotide using a tunable VLP drug delivery nanocontainer to cross the BBB.