Saratov State University, 83 Astrakhanskaya st., Saratov 410012, Russia.
Peoples' Friendship University of Russia, 6 Mikluho-Maklaya St., Moscow 117198, Russia.
ACS Biomater Sci Eng. 2020 Jan 13;6(1):389-397. doi: 10.1021/acsbiomaterials.9b01669. Epub 2019 Dec 19.
Polyelectrolyte microcapsules and other targeted drug delivery systems could substantially reduce the side effects of drug and overall toxicity. At the same time, the cardiovascular system is a unique transport avenue that can deliver drug carriers to any tissue and organ. However, one of the most important potential problems of drug carrier systemic administration in clinical practice is that the carriers might cause circulatory disorders, the development of pulmonary embolism, ischemia, and tissue necrosis due to the blockage of small capillaries. Thus, the presented work aims to find out the processes occurring in the bloodstream after the systemic injection of polyelectrolyte capsules that are 5 μm in size. It was shown that 1 min after injection, the number of circulating capsules decreases several times, and after 15 min less than 1% of the injected dose is registered in the blood. By this time, most capsules accumulate in the lungs, liver, and kidneys. However, magnetic field action could slightly increase the accumulation of capsules in the region-of-interest. For the first time, we have investigated the real-time blood flow changes in vital organs in vivo after intravenous injection of microcapsules using a laser speckle contrast imaging system. We have demonstrated that the organism can adapt to the emergence of drug carriers in the blood and their accumulation in the vessels of vital organs. Additionally, we have evaluated the safety of the intravenous administration of various doses of microcapsules.
聚电解质微胶囊和其他靶向药物输送系统可以显著降低药物的副作用和整体毒性。同时,心血管系统是一种独特的输送途径,可以将药物载体输送到任何组织和器官。然而,药物载体系统给药在临床实践中最重要的潜在问题之一是载体可能会由于小毛细血管阻塞而导致循环障碍、肺栓塞、缺血和组织坏死。因此,本工作旨在研究在全身注射 5μm 大小的聚电解质胶囊后血液中发生的过程。结果表明,注射后 1 分钟,循环胶囊的数量减少了几倍,15 分钟后,血液中的注射剂量不到 1%。此时,大多数胶囊积聚在肺、肝和肾中。然而,磁场作用可以略微增加感兴趣区域中胶囊的积累。我们首次使用激光散斑对比成像系统研究了微胶囊静脉注射后体内重要器官的实时血流变化。我们已经证明,机体可以适应血液中药物载体的出现及其在重要器官血管中的积累。此外,我们还评估了静脉给予不同剂量微胶囊的安全性。