Magnetic Liposomes for Remote Controlled High-Molecular Drugs Release under a Low-Frequency Non-Heating Magnetic Field
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etic Liposomes for Remote Controlled High-Molecular Drugs Release under a Low-Frequency Non-Heating Magnetic Field K. Yu. Vlasovaa, **, S. Ch. Vanzarakshaevaa, M. M. Veselova, I. M. Le-Deygena, A. V. Petrunina, A. N. Prusovb, A. B. Shuklinovc, Yu. I. Golovina, c, A. V. Kabanova, d, and N. L. Klyachkoa, c, d, * a
b
Department of Chemistry, Moscow State University, Moscow, 119991 Russia Belozersky Research Institute of Physical Chemical Biology, Moscow State University, Moscow, 119991 Russia c Derzhavin Tambov State University, Tambov, 392000 Russia dCenter for Nanotechnology in Drug Delivery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599 United States *e-mail: [email protected] **e-mail: [email protected] Received February 2, 2020; revised February 12, 2020; accepted February 20, 2020
Abstract—Magnetic anionic liposomes (MALip) conjugated with magnetite magnetic nanoparticles (MNPs) are developed for the controlled release of a protease inhibitor (BBI) under exposure to a low-frequency nonheating magnetic field (LF AMF). It is shown that an increase of up to 35% of the protein release rate occurred when the MALip are exposed to the LF AMF (frequency 110 Hz, intensity 75–150 kA/m) for 5–15 min. The research provides prospects for the development of remotely controlled protein release from liposomes. Keywords: magnetic liposomes, non-heating alternating magnetic field, controlled release of macromolecular compounds (proteins) DOI: 10.3103/S0027131420040112
INTRODUCTION Liposomes have many advantages over other drug delivery systems; however, at the same time they have a number of drawbacks, the most significant of which is the low rate of release of encapsulated molecules. The influence of a non-heating low-frequency magnetic field (LF AMF) with frequency f below 1000 Hz is the most promising among multiple approaches to the stimulus-driven drug release from liposomes [1–7]. These fields are safe for humans even at large intensity levels, penetrate deep into biological tissues, and can act selectively on magnetically sensitive materials introduced into the organism without affecting the surrounding organs and tissues [8]. Earlier we demonstrated that the LF AMF influencing magnetic liposomes with MNPs in their membranes can be used to remotely control the release of low-molecular-weight compounds from the vesicles [9]. The LF AMF decreases the stability of the lipid bilayer of magnetic liposomes (via the mechanical effect on the MNPs), which experience Brown relaxAbbreviations: LF AMF, low-frequency alternating magnetic field; ALip, anionic liposomes; MALip, magnetic anionic liposomes; MNP, magnetic nanoparticle; f-MNP, functionalized magnetic nanoparticle; BBI, Bowman–Birk protease inhibitor.
ation [10]. The rotational-vibrational movement of the particles in the LF AMF can cause a mechanical strain in the membrane, leading to its disordering and, hence, to a decrease in permeability for small molecules. This approach is an alternative to magnetic hyperthermia, the met
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