Long-acting tunable release of amlodipine loaded PEG-PCL micelles for tailored treatment of chronic hypertension.
Long-acting tunable release of amlodipine loaded PEG-PCL micelles for tailored treatment of chronic hypertension.
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DOI：
10.1016/j.nano.2021.102417
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发表时间：
2021-10
期刊：
影响因子：
--
通讯作者：
Grattoni A
中科院分区：
文献类型：
--
作者：
Di Trani N;Liu HC;Qi R;Viswanath DI;Liu X;Chua CYX;Grattoni A
高血压是一种慢性疾病，需要终身治疗管理。严格遵守给药时间可以提高疗效，而依从性差则会导致安全性问题。鉴于这些挑战，我们提出了一种纳米流体技术，使长效药物输送与可调定时的药物管理使用埋栅电极在纳米通道。我们开发了一种聚乙二醇甲基醚-嵌段-聚（ε-己内酯）（PEG-PCL）为基础的胶束制剂的阿苯磺酸，钙通道阻滞剂治疗高血压。带静电的PEG-PCL胶束制剂增强了药物溶解度，并使其对纳米通道中的静电释放门控产生响应，以在临床相关治疗剂量下持续释放。使用低功率（<3 VDC）门控电位，我们证明了氨氯地平负载胶束的可调释放。此外，我们发现，释放的药物通过钙离子阻断体外保持生物活性。这项研究为我们的慢性高血压管理策略的潜在适用性提供了概念证明。在这里，我们开发了一种用于高血压的时间疗法，通过利用静电门控纳米流体膜与基于PEG-PCL的阿苯磺酸盐制剂。使用具有静电门控能力的纳米流体膜，我们调制了跨膜胶束的释放速率。该技术原则上可以实现循环输送，其可以被预编程以反映昼夜血压活动，并被远程控制以进行剂量调整。
Hypertension is a chronic condition that requires lifelong therapeutic management. Strict adherence to drug administration timing improves efficacy, while poor adherence leads to safety concerns. In light of these challenges, we present a nanofluidic technology that enables long-acting drug delivery with tunable timing of drug administration using buried gate electrodes in nanochannels. We developed a Poly(ethylene glycol) methyl ether-block-poly(ε-caprolactone) (PEG-PCL)-based micellar formulation of amlodipine besylate, a calcium channel blocker for hypertension treatment. The electrostatically charged PEG-PCL micellar formulation enhanced drug solubility and rendered amlodipine responsive to electrostatic release gating in nanochannels for sustained release at clinically relevant therapeutic dose. Using a low-power (<3 VDC) gating potential, we demonstrated tunable release of amlodipine-loaded micelles. Additionally, we showed that the released drug maintained biological activity via calcium ion blockade in vitro. This study represents a proof of concept for the potential applicability of our strategy for chronotherapeutic management of hypertension. Here we developed a chronotherapy for hypertension by leveraging electrostatic-gated nanofluidic membrane with PEG-PCL based formulation of amlodipine besylate. Using a nanofluidic membrane with electrostatic gating capabilities, we modulated the release rate of micellar amlodipine across the membrane. This technology could in principle achieve a cyclic delivery that can be pre-programmed to mirror the circadian blood pressure activity and remotely controlled for dose adjustment.
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