Effectivity and safety studying of microcapsules intra-arterial delivery in the kidney by the optical monitoring of hemodynamic
Olga A. Sindeeva‡,†, Arkady S. Abdurashitov‡, Ekaterina S. Prikhozhdenko†, Oksana A. Mayorova†, Olga I. Gusliakova†, Natalia A. Shushunova†, Valentina O. Plastun†, Valery V. Tuchin† and Gleb B. Sukhorukov‡,#
‡Skolkovo Institute of Science and Technology, Skolkovo Innovation Center, Building 3, Moscow, 143026, Russia.
†Saratov State University, 83 Astrakhanskaya str., Saratov 410012, Russia.
#School of Engineering and Materials Science, Queen Mary University of London, Mile End, Eng, 215, London E1 4NS, United Kingdom.
Abstract
Targeting drug delivery systems is one of the important keys to reducing the side effects of systemic therapy. Many of them can provide both prolonged and controlled release of the encapsulated substance, but all of them not effective for drug delivery in the kidney. It is due to the systemic dispersion in the organ’s vessels after vein injection and accumulation in the liver. Renal artery injection of micron-size drug carriers provides an effective local accumulation and even distribution in kidney glomeruli but may cause irreversible vessel blockage. Therefore, it is important to provide correct administration procedure and find the most effective and safe dose for the selected carrier type. In our work, we have shown that laser speckle contrast analysis in combination with optical coherence tomography is a good way for vital assessment of the hemodynamic changes in the superficial layers of the mouse kidney (glomeruli localization area) after renal artery injection of microcapsules. Injection of the 3-μm sized fluorescent capsules based on poly-L-arginine and dextran sulfate at doses not exceeding 20 million capsules per mouse was followed by a sharp decrease in blood flow (about 30-50%) with subsequent restoration after 24 hours. In this case, a pronounced vascular network was visualized before, 15, and 45 minutes after the capsules injection using optical coherence tomography. At the same time, increasing the dose up to 30 million per mouse resulted in the irreversible decrease in blood flow (by 80–90%) in most cases, which did not recover after 24 hours. At the same time, we observed only a weak signal from the vessels 15 minutes after the injection, which almost completely disappeared after 45 minutes, which indicates by total blockage of the vessels and circulatory arrest. Histological analysis also revealed extensive ischemic damages of renal tissue 5 days after intra-arterial injection of capsules only at the largest dose (30 million) and did not reveal any changes at the dose of 20 million or less. Thus, the control of hemodynamic parameters using optical methods allows to reliably judge the safety of the selected dosage.
This work was supported by Russian Science Foundation (project no. 19-75-10043).
Speaker
Olga Sindeeva
Skolkovo Institute of Science and Technology
Russia
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