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Renal Artery Catheterization for Microcapsules’Targeted Delivery to the Mouse Kidney
Pharmaceutics ( IF 4.9 ) Pub Date : 2022-05-14 , DOI: 10.3390/pharmaceutics14051056
Olga I Gusliakova 1 , Ekaterina S Prikhozhdenko 1 , Valentina O Plastun 1 , Oksana A Mayorova 1 , Natalia A Shushunova 1 , Arkady S Abdurashitov 2 , Oleg A Kulikov 3 , Maxim A Abakumov 4 , Dmitry A Gorin 5 , Gleb B Sukhorukov 2, 6 , Olga A Sindeeva 1, 2
Affiliation  

The problem of reducing the side effects associated with drug distribution throughout the body in the treatment of various kidney diseases can be solved by effective targeted drug delivery. The method described herein involves injection of a drug encapsulated in polyelectrolyte capsules to achieve prolonged local release and long-term capillary retention of several hours while these capsules are administered via the renal artery. The proposed method does not imply disruption (puncture) of the renal artery or aorta and is suitable for long-term chronic experiments on mice. In this study, we compared how capsule size and dosage affect the target kidney blood flow. It has been established that an increase in the diameter of microcapsules by 29% (from 3.1 to 4.0 μm) requires a decrease in their concentration by at least 50% with the same suspension volume. The photoacoustic method, along with laser speckle contrast imaging, was shown to be useful for monitoring blood flow and selecting a safe dose. Capsules contribute to a longer retention of a macromolecular substance in the target kidney compared to its free form due to mechanical retention in capillaries and slow impregnation into surrounding tissues during the first 1–3 h, which was shown by fluorescence tomography and microscopy. At the same time, the ability of capillaries to perform almost complete “self-cleaning” from capsular shells during the first 12 h leads to the preservation of organ tissues in a normal state. The proposed strategy, which combines endovascular surgery and the injection of polymer microcapsules containing the active substance, can be successfully used to treat a wide range of nephropathies.

中文翻译:

肾动脉导管插入术将微胶囊靶向输送至小鼠肾脏

在治疗各种肾脏疾病时,通过有效的靶向药物输送可以解决减少与全身药物分布相关的副作用的问题。本文描述的方法涉及注射封装在聚电解质胶囊中的药物,以实现延长的局部释放和数小时的长期毛细血管滞留,同时这些胶囊通过肾动脉施用。所提出的方法并不意味着肾动脉或主动脉的破坏(穿刺),并且适用于小鼠的长期慢性实验。在这项研究中,我们比较了胶囊大小和剂量如何影响目标肾血流量。已证实微胶囊的直径增加了 29%(从 3.1 增加到 4.0)μm) 要求在相同的悬浮液体积下其浓度至少降低 50%。光声方法与激光散斑对比成像一起被证明可用于监测血流和选择安全剂量。荧光断层扫描和显微镜显示,由于毛细血管中的机械滞留和在前 1-3 小时内缓慢浸渍到周围组织中,与游离形式相比,胶囊有助于大分子物质在目标肾脏中的滞留时间更长。同时,毛细血管在最初的12小时内对囊壳进行几乎完全的“自清洁”的能力导致器官组织保持正常状态。所提出的策略结合了血管内手术和注射含有活性物质的聚合物微胶囊,可成功用于治疗多种肾病。
更新日期:2022-05-14
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