Fluorescent liposomal nanocarriers for targeted drug delivery in ischemic stroke therapy.
Fluorescent liposomal nanocarriers for targeted drug delivery in ischemic stroke therapy.
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DOI：
10.1039/d3bm00951c
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发表时间：
2023-12-05
影响因子：
6.6
通讯作者：
中科院分区：
文献类型：
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缺血性脑卒中导致急性中枢神经系统损伤和长期残疾，治疗选择有限，例如手术清除血栓或溶栓药物。需要神经保护疗法来保护脆弱的脑区。嘌呤能受体P2X4在脑卒中期间被激活，并加剧脑卒中后的损伤。化合物5 - (3 - 溴苯基) - 1,3 - 二氢 - 2H - 苯并呋喃[3,2 - e] - 1,4 - 二氮杂卓 - 2 - 酮（5BDBD）抑制P2X4，并在啮齿动物中显示出神经保护作用。然而，将其配制成可全身递送至中枢神经系统的制剂很困难。当前的手稿首次报道了5BDBD聚乙二醇化脂质体制剂的合成与表征，并评估了它们在临床前小鼠模型中治疗脑卒中的可行性。合成并表征了一种5BDBD的聚乙二醇化脂质体制剂，其包封率>80%，并在48小时内释放。用尼罗红包封进行的体外和体内实验显示了纳米载体的细胞相容性和中枢神经系统浸润性。在脑卒中发作后4小时或28小时给药，该纳米制剂提供了显著的神经保护作用，与对照组相比，梗死体积减少了约50%。它以较低的剂量和较短的治疗时间优于口服给药的5BDBD，这表明纳米制剂的精确递送可改善治疗效果。荧光纳米制剂可作为递送和追踪治疗脑卒中的治疗药物的平台。
缺血性脑卒中导致急性中枢神经系统疾病。本文介绍了一种用于治疗缺血性脑卒中的5 - BDBD和尼罗红的可注射脂质体纳米颗粒制剂。
Ischemic stroke causes acute CNS injury and long-term disability, with limited treatment options such as surgical clot removal or clot-busting drugs. Neuroprotective therapies are needed to protect vulnerable brain regions. The purinergic receptor P2X4 is activated during stroke and exacerbates post-stroke damage. The chemical compound 5-(3-Bromophenyl)-1,3-dihydro-2H-Benzofuro[3,2-e]-1,4-diazepin-2-one (5BDBD) inhibits P2X4 and has shown neuroprotective effects in rodents. However, it is difficult to formulate for systemic delivery to the CNS. The current manuscript reports for the first time, the synthesis and characterization of 5BDBD PEGylated liposomal formulations and evaluates their feasibility to treat stroke in a preclinical mice model. A PEGylated liposomal formulation of 5BDBD was synthesized and characterized, with encapsulation efficacy of >80%, and release over 48 hours. In vitro and in vivo experiments with Nile red encapsulation showed cytocompatibility and CNS infiltration of nanocarriers. Administered 4 or 28 hours after stroke onset, the nanoformulation provided significant neuroprotection, reducing infarct volume by ∼50% compared to controls. It outperformed orally-administered 5BDBD with a lower dose and shorter treatment duration, suggesting precise delivery by nanoformulation improves outcomes. The fluorescent nanoformulations may serve as a platform for delivering and tracking therapeutic agents for stroke treatment. Ischemic Stroke causes acute CNS disorders. This article represents an injectable liposomal nanoparticle formulation of 5-BDBD and Nile red for treatment of Ischemic Stroke.
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DOI：
10.2147/dddt.s56071
发表时间：
2015
期刊：
Drug design, development and therapy
影响因子：
--
作者：
Fluri F;Schuhmann MK;Kleinschnitz C
通讯作者：
Kleinschnitz C
DOI：
10.1016/s1474-4422(17)30299-5
发表时间：
2017-11
期刊：
The Lancet. Neurology
影响因子：
--
作者：
GBD 2015 Neurological Disorders Collaborator Group
通讯作者：
GBD 2015 Neurological Disorders Collaborator Group
影响因子：
4.7
作者：
Achar A;Myers R;Ghosh C
通讯作者：
Ghosh C
DOI：
10.3390/molecules26092591
发表时间：
2021-04-29
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Duong TT;Isomäki A;Paaver U;Laidmäe I;Tõnisoo A;Yen TTH;Kogermann K;Raal A;Heinämäki J;Pham TM
通讯作者：
Pham TM
影响因子：
12.4
作者：
Al-Ahmady, Zahraa S.;Dickie, Ben R.;Aldred, Isabelle;Jasim, Dhifaf A.;Barrington, Jack;Haley, Michael;Lemarchand, Eloise;Coutts, Graham;Kaur, Satinderdeep;Bates, Jessica;Curran, Sarah;Goddard, Ruth;Walker, Megan;Parry-jones, Adrian;Kostarelos, Kostas;Allan, Stuart M.
通讯作者：
Allan, Stuart M.