Effect of Systemic Polyelectrolyte Microcapsule Administration on the Blood Flow Dynamics of Vital Organs

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. © 2019 American Chemical Society.

Sindeeva O.A. 1, 2 , Verkhovskii R.A.1, 3 , Abdurashitov A.S.1, 9 , Voronin D.V.1, 10 , Gusliakova O.I.1, 6 , Kozlova A.A.1 , Mayorova O.A.1 , Ermakov A.V.1 , Lengert E.V.1, 4 , Navolokin N.A.5 , Tuchin V.V.1, 10, 11 , Gorin D.A.6 , Sukhorukov G.B. 2, 6, 7 , Bratashov D.N.1, 8
American Chemical Society
  • 1 Saratov State University, 83 Astrakhanskaya st., Saratov, 410012, Russian Federation
  • 2 Peoples' Friendship University of Russia, 6 Mikluho-Maklaya St., Moscow, 117198, Russian Federation
  • 3 Yuri Gagarin State Technical University of Saratov, 77 Politekhnicheskaya st., Saratov, 410054, Russian Federation
  • 4 Ghent University, 653 Coupure Links, Ghent, 9000, Belgium
  • 5 Saratov State Medical University, 112 Bolshaya Kazachia st., Saratov, 410012, Russian Federation
  • 6 Skolkovo Institute of Science and Technology, 3 Nobelya st., Moscow, 121205, Russian Federation
  • 7 Queen Mary University of London, Mile End Road, London, E1 4NS, United Kingdom
  • 8 Moscow Institute of Physics and Technology, 9 Institutskiy per., Dolgoprudny, Moscow, 141701, Russian Federation
  • 9 Tomsk State University, 36 Lenin Ave., Tomsk, 634050, Russian Federation
  • 10 National University of Oil and Gas, Gubkin University, 65 Leninsky Prospekt, Moscow, 119991, Russian Federation
  • 11 Institute of Precision Mechanics and Control, Russian Academy of Sciences, 24 Rabochaya St., Saratov, 410028, Russian Federation
adaptation; autoregulation; blood flow; embolism; imaging flow cytometry; intravenous injection; microcapsules; microcirculation; physiological stress; speckle contrast imaging; systemic administration
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