Pharmacokinetics and fate of free and encapsulated IRD800CW-labelled human BChE intravenously administered in mice.

Autor: Pashirova T; Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, 18 Kremlyovskaya St., Russian Federation; Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, Arbuzov Str. 8, 420088 Kazan, Russian Federation. Electronic address: tatyana_pashirova@mail.ru., Shaihutdinova Z; Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, 18 Kremlyovskaya St., Russian Federation; Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, Arbuzov Str. 8, 420088 Kazan, Russian Federation., Tatarinov D; Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, Arbuzov Str. 8, 420088 Kazan, Russian Federation., Titova A; Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, 18 Kremlyovskaya St., Russian Federation., Malanyeva A; Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, 18 Kremlyovskaya St., Russian Federation., Vasileva O; Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, 18 Kremlyovskaya St., Russian Federation., Gabdurakhmanov K; Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, 18 Kremlyovskaya St., Russian Federation., Dudnikov S; Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, 18 Kremlyovskaya St., Russian Federation., Schopfer LM; University of Nebraska Medical Center, Eppley Institute, Omaha, NE, USA., Lockridge O; University of Nebraska Medical Center, Eppley Institute, Omaha, NE, USA., Masson P; Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, 18 Kremlyovskaya St., Russian Federation. Electronic address: pym.masson@free.fr.
Jazyk: angličtina
Zdroj: International journal of biological macromolecules [Int J Biol Macromol] 2024 Dec; Vol. 282 (Pt 6), pp. 137305. Date of Electronic Publication: 2024 Nov 07.
DOI: 10.1016/j.ijbiomac.2024.137305
Abstrakt: Human butyrylcholinesterase (BChE) is an efficient bioscavenger of toxicants. Highly purified BChE was labelled with the near infrared fluorescent IRDye800CW. The goal was to determine the pharmacokinetics and fate of enzyme in mice. BChE-IRDye800CW was encapsulated in polyethylene glycol-polypropylene sulfide-based spherical polymersome nanoreactors with the following characteristics: 140 nm diameter, ξ = -6 mV, PDI ≤ 0.2, 1 year stability. Encapsulation did not alter the functional properties of BChE. Free and encapsulated enzyme were injected intravenously to CD-1 mice (single dose of enzyme 1.5 mg/kg and PEG-PPS polymersomes 25 mg/kg) and were analyzed for 8 days using an in vivo imaging system. Results showed that the pharmacokinetic distribution α-phase of encapsulated BChE (t 1/2  = 17.6 h) was longer than for free enzyme (t 1/2  = 6.6 h). The mean half-time for elimination β-phase was 2-time longer for encapsulated enzyme than for free enzyme (150 vs 72 h). Transient changes in infrared fluorescence in organs showed that BChE is eliminated from liver. However, free and encapsulated enzymes were cleared via different pathways. This first study of pharmacokinetics and fate of BChE encapsulated in polymersomes initiates research of new formulations of bioscavengers aimed at increasing the residence time of enzymes in the blood stream.
Competing Interests: Declaration of competing interest The authors declare no conflicts of interest.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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