Biodegradable Therapeutic Microneedle Patch for Rapidly Antihypertensive Treatment.
Biodegradable Therapeutic Microneedle Patch for Rapidly Antihypertensive Treatment.
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DOI：
10.1021/acsami.9b09697
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发表时间：
2019-08
影响因子：
9.5
通讯作者：
Yan Li;Fanmao Liu;C. Su;Bing-bo Yu;Di Liu;Hui-Jiuan Chen;Di-an Lin;Chengduan Yang;Lingfei Zhou;Qianni Wu;Wen-hao Xia;Xi Xie;Jun Tao
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作者：
Yan Li;Fanmao Liu;C. Su;Bing-bo Yu;Di Liu;Hui-Jiuan Chen;Di-an Lin;Chengduan Yang;Lingfei Zhou;Qianni Wu;Wen-hao Xia;Xi Xie;Jun Tao
高血压急症可引起严重的心血管疾病并伴有急性靶器官损害，需要迅速平稳的降压。目前用于治疗高血压急症的药物，如硝普钠（SNP），需要仔细控制剂量以避免副作用（例如氰化物中毒）。SNP的临床给药方式为静脉注射或滴注，进一步限制了其在急救或急救中的应用。在这里，我们开发了一种抗高血压微针（aH-MN）技术，以无痛的方式经皮递送SNP与硫代硫酸钠（ST）作为氰化物解毒剂的组合。通过离心浇铸法制备了负载SNP和ST的可溶性微针，其中SNP稳定地包装在微针中，并且当aH-MN穿透皮肤时，SNP将立即通过皮下毛细血管释放到体循环中。在自发性高血压大鼠（SHR）模型上观察其降压作用。通过aH-MN治疗实现了快速有效的BP降低，满足了高血压急症的临床BP控制要求。评估了aH-MNs疗法的副作用，包括皮肤刺激和靶器官损伤，并且ST的组合递送有效地抑制了由连续摄入SNP引起的这些副作用。本研究介绍了一种有效和患者友好的抗高血压治疗，具有良好的副作用，特别是一种可控和自我管理的方法来治疗高血压急症。
Hypertensive emergency causes severe cardiovascular diseases accompanied with acute target organ damages, requiring rapid and smooth blood pressure (BP) reduction. Current medicine for treating hypertensive emergencies, such as sodium nitroprusside (SNP), requires careful dose control to avoid side effects (e.g. cyanide poisoning). The clinical administrations of SNP using intravenous injection or drip further restrict its usage for the first-aid or the self-aid of emergencies. Here we developed an antihypertensive microneedle (aH-MN) technique to transdermally deliver SNP in combination with sodium thiosulfate (ST) as a cyanide antidote in a painless way. Dissolvable microneedles loaded with SNP and ST were fabricated via centrifugation casting method, where the SNP were stably packaged in microneedles, and would be immediately released into the systemic circulation via subcutaneous capillaries when aH-MNs penetrated the skin. The antihypertensive effects were demonstrated on spontaneously hypertensive rats (SHRs) model. Rapid and potent BP reduction was achieved via aH-MNs treatment, fulfilling clinical BP-control requirements for hypertensive emergencies. The side effects include skin irritation and target organ damage of aH-MNs therapies were evaluated, and the combinative delivery of ST effectively suppressed these side effects induced by the consecutive intake of SNP. This study introduces an efficient and patient-friendly antihypertensive therapy with a favorable side effects profile, particularly a controllable and self-administrable approach to treat hypertensive emergency.