4.7 Article

Renal Artery Catheterization for Microcapsules' Targeted Delivery to the Mouse Kidney

期刊

PHARMACEUTICS
卷 14, 期 5, 页码 -

出版社

MDPI
DOI: 10.3390/pharmaceutics14051056

关键词

renal artery catheterization; polyelectrolyte microcapsules; targeted delivery; mouse kidney; biodistribution; migration; blood flow; optoacoustic mesoscopy; laser speckle contrast imaging

资金

  1. Russian Science Foundation [19-75-10043]
  2. Russian Science Foundation [19-75-10043] Funding Source: Russian Science Foundation

向作者/读者索取更多资源

The problem of reducing side effects in drug distribution for kidney disease treatment can be solved with targeted drug delivery. This study focuses on using polyelectrolyte capsules injected through the renal artery to achieve prolonged local drug release and capillary retention. The method is non-invasive and suitable for long-term experiments in mice. The study also explores the effects of capsule size and dosage on target kidney blood flow, and suggests a combination of endovascular surgery and injection of polymer microcapsules as a successful strategy for treating nephropathies.
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 mu m) 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.

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