2. Academic Validation
  3. BODIPY-labelled acetylcholinesterase reactivators can be encapsulated into ferritin nanovehicles for enhanced bioavailability in the CNS

BODIPY-labelled acetylcholinesterase reactivators can be encapsulated into ferritin nanovehicles for enhanced bioavailability in the CNS

  • Biomed Pharmacother. 2023 Nov:167:115490. doi: 10.1016/j.biopha.2023.115490.
Eliska Prchalova 1,  Martina Sukupova 2,  David Malinak 3,  Rudolf Andrys 1,  Ladislav Sivak 4,  Vladimir Pekarik 4,  Adam Skarka 1,  Jana Svobodova 1,  Lukas Prchal 5,  Lukas Fresser 1,  Zbynek Heger 6,  Kamil Musilek 7
Affiliations

Affiliations

  • 1 University of Hradec Kralove, Faculty of Science, Department of Chemistry, Rokitanskeho 62, 500 03 Hradec Kralove, Czech Republic.
  • 2 Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, CZ-613 00 Brno, Czech Republic; Department of Experimental Biology, Faculty of Science, Masaryk University, CZ-625 00 Brno, Czech Republic.
  • 3 University of Hradec Kralove, Faculty of Science, Department of Chemistry, Rokitanskeho 62, 500 03 Hradec Kralove, Czech Republic; University Hospital in Hradec Kralove, Biomedical Research Centre, Sokolska 581, 500 05 Hradec Kralove, Czech Republic.
  • 4 Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, CZ-613 00 Brno, Czech Republic.
  • 5 University Hospital in Hradec Kralove, Biomedical Research Centre, Sokolska 581, 500 05 Hradec Kralove, Czech Republic.
  • 6 Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, CZ-613 00 Brno, Czech Republic. Electronic address: [email protected].
  • 7 University of Hradec Kralove, Faculty of Science, Department of Chemistry, Rokitanskeho 62, 500 03 Hradec Kralove, Czech Republic. Electronic address: [email protected].
PMID: 37722189 DOI: 10.1016/j.biopha.2023.115490
Abstract

The BODIPY-labelled oxime reactivator was prepared and used to study its biodistribution into central nervous system. The newly synthesized oxime was found to be weak inhibitor of acetylcholinesterase and strong inhibitor of butyrylcholinesterase. Its reactivation ability for organophosphate inhibited acetylcholinesterase was found similar to a parent oxime. The BODIPY-labelled oxime was further encapsulated into recombinant human H-ferritin and evaluated in vitro and in vivo. The oxime or encapsulated oxime were found to be bioaccumulated primarily in liver and kidneys of mice, but some amount was distributed also to the brain, where it was detectable even after 24 h. The BODIPY-labelled oxime encapsulated to human H-ferritin showed better CNS bioaccumulation and tissue retention at 8 and 24 h time points compared to free oxime, although the fluorescence results might be biased due to BODIPY metabolites identified in tissue homogenates. Taken together, the study demonstrates the first utilization of recombinant ferritins for changing the unfavourable pharmacokinetics of oxime reactivators and brings promising results for follow-up studies.

Keywords

BODIPY; Cholinesterase; Encapsulation; Organophosphate; Oxime; Reactivation.

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