Liposome-encapsulated aprotinin biodistribution in mice: Side-by-side comparison with free drug formulation.

Autor: Mochalova EN; Moscow Institute of Physics and Technology, 1А Kerchenskaya St, 117303, Moscow, Russia; Sirius University of Science and Technology, 1 Olimpiyskiy Ave, 354340, Sirius, Krasnodar region, Russia; Prokhorov General Physics Institute of the Russian Academy of Sciences, 38 Vavilov St, 119991, Moscow, Russia., Cherkasov VR; Moscow Institute of Physics and Technology, 1А Kerchenskaya St, 117303, Moscow, Russia; Prokhorov General Physics Institute of the Russian Academy of Sciences, 38 Vavilov St, 119991, Moscow, Russia., Sizikov AA; Moscow Institute of Physics and Technology, 1А Kerchenskaya St, 117303, Moscow, Russia., Litvinenko AV; Moscow Institute of Physics and Technology, 1А Kerchenskaya St, 117303, Moscow, Russia., Vorobeva TS; Moscow Institute of Physics and Technology, 1А Kerchenskaya St, 117303, Moscow, Russia., Norvillo NB; Moscow Institute of Physics and Technology, 1А Kerchenskaya St, 117303, Moscow, Russia., Gopanenko AV; Sirius University of Science and Technology, 1 Olimpiyskiy Ave, 354340, Sirius, Krasnodar region, Russia., Ivashchenko IA; Moscow Institute of Physics and Technology, 1А Kerchenskaya St, 117303, Moscow, Russia., Nikitin MP; Sirius University of Science and Technology, 1 Olimpiyskiy Ave, 354340, Sirius, Krasnodar region, Russia; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 16/10 Miklukho-Maklaya St, 117997, Moscow, Russia; Moscow Center for Advanced Studies, 20 Kulakova St, 123592, Moscow, Russia. Electronic address: nikitin.mp@talantiuspeh.ru., Ivashchenko AA; ChemRar RDI, LLC, 40 Bolshoy Blvd, 121205, Moscow, Russia.
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2024 Nov 19; Vol. 734, pp. 150636. Date of Electronic Publication: 2024 Aug 31.
DOI: 10.1016/j.bbrc.2024.150636
Abstrakt: Injuries of the respiratory system caused by viral infections (e.g., by influenza virus, respiratory syncytial virus, metapneumovirus, or coronavirus) can lead to long-term complications or even life-threatening conditions. The challenges of treatment of such diseases have become particularly pronounced during the recent pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). One promising drug is the anti-fibrinolytic and anti-inflammatory protease inhibitor aprotinin, which has demonstrated considerable inhibition of the replication of some viruses. Encapsulation of aprotinin in liposomes can significantly improve the effectiveness of the drug, however, the use of nanoparticles as carriers of aprotinin can radically change its biodistribution in the body. Here we show that the liposomal form of aprotinin accumulates more efficiently in the lungs, heart, and kidneys than the molecular form by side-by-side comparison of the ex vivo biodistribution of these two fluorescently labeled formulations in mice using bioimaging. In particular, we synthesized liposomes of different compositions and studied their accumulation in various organs and tissues. Direct comparison of the biodistributions of liposomal and free aprotinin showed that liposomes accumulated in the lungs 1.82 times more effectively, and in the heart and kidneys - 3.56 and 2.00 times, respectively. This suggests that the liposomal formulation exhibits a longer residence time in the target organ and, thus, has the potential for a longer therapeutic effect. The results reveal the great potential of the aprotinin-loaded liposomes for the treatment of respiratory system injuries and heart- and kidney-related complications of viral infections.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. E.N.M. and M.P.N. are stakeholders of Abisense LLC that manufactures the LumoTrace FLUO bioimaging system. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE