title: In Vitro and in Vivo Visualization and Trapping of Fluorescent Magnetic Microcapsules in a Bloodstream.
abstract: Remote navigation and targeted delivery of biologically active compounds is one of the current challenges in the development of drug delivery systems. Modern methods of micro- and nanofabrication give us new opportunities to produce particles and capsules bearing cargo to deploy and possess magnetic properties to be externally navigated. In this work we explore multilayer composite magnetic microcapsules as targeted delivery systems in vitro and in vivo studies under natural conditions of living organism. Herein, we demonstrate magnetic addressing of fluorescent composite microcapsules with embedded magnetite nanoparticles in blood flow environment. First, the visualization and capture of the capsules at the defined blood flow by the magnetic field are shown in vitro in an artificial glass capillary employing a wide-field fluorescence microscope. Afterward, the capsules are visualized and successfully trapped in vivo into externally exposed rat mesentery microvessels. Histological analysis shows that capsules infiltrate small mesenteric vessels whereas large vessels preserve the blood microcirculation. The effect of the magnetic field on capsule preferential localization in bifurcation areas of vasculature, including capsule retention at the site once external magnet is switched off is discussed. The research outcome demonstrates that microcapsules can be effectively addressed in a blood flow, which makes them a promising delivery system with remote navigation by the magnetic field.
authors.forename: Denis V
authors.identifier: http://orcid.org/0000-0002-1960-6737
authors.initials: DV
authors.lastname: Voronin
authors.forename: Olga A
authors.initials: OA
authors.lastname: Sindeeva
authors.forename: Maxim A
authors.initials: MA
authors.lastname: Kurochkin
authors.forename: Oksana
authors.initials: O
authors.lastname: Mayorova
authors.forename: Ivan V
authors.initials: IV
authors.lastname: Fedosov
authors.forename: Oksana
authors.initials: O
authors.lastname: Semyachkina-Glushkovskaya
authors.forename: Dmitry A
authors.initials: DA
authors.lastname: Gorin
authors.affiliation: Interdisciplinary Laboratory of Biophotonics, National Research Tomsk State University , Tomsk 634050, Russia.|Laboratory of Laser Diagnostics of Technical and Living Systems, Precision Mechanics and Control Institute of the Russian Academy of Sciences , Saratov 410028, Russia.
authors.forename: Valery V
authors.initials: VV
authors.lastname: Tuchin
authors.affiliation: School of Engineering and Materials Science, Queen Mary University of London , Mile End Road, London E1 4NS, United Kingdom.
authors.forename: Gleb B
authors.initials: GB
authors.lastname: Sukhorukov
mesh_terms: D000818:Animals; D002214:Capsules; D016503:Drug Delivery Systems; D008280:Magnetics; D058185:Magnetite Nanoparticles; D051381:Rats
chemical_list: D002214:Capsules; D058185:Magnetite Nanoparticles
keywords: Fe3O4 nanoparticles; blood flow; drug delivery; fluorescent magnetic microcapsules; rat mesentery; wide-field illumination laser microscope