Nanosystems for targeted delivery and remote-controlled release of therapeutic agents has become a top priority in pharmaceutical science and drug development in recent decades. Application of a low frequency magnetic field (LFMF) as an external stimulus opens up opportunities to trigger release of the encapsulated bioactive substances with high locality and penetration ability without heating of biological tissue in vivo. Therefore, the development of novel microencapsulated drug formulations sensitive to LFMF is of paramount importance. Here, we report the result of LFMF-triggered release of the fluorescently labeled dextran from polyelectrolyte microcapsules modified with magnetic iron oxide nanoparticles. Polyelectrolyte microcapsules were obtained by a method of sequential deposition of oppositely charged poly(allylamine hydrochloride) (PAH) and poly(sodium 4-styrenesulfonate) (PSS) on the surface of colloidal vaterite particles. The synthesized single domain maghemite nanoparticles integrated into the polymer multilayers serve as magneto-mechanical actuators. We report the first systematic study of the effect of magnetic field with different frequencies on the permeability of the microcapsules. The in situ measurements of the optical density curves upon the 100 mT LFMF treatment were carried out for a range of frequencies from 30 to 150 Hz. Such fields do not cause any considerable heating of the magnetic nanoparticles but promote their rotating-oscillating mechanical motion that produces mechanical forces and deformations of the adjacent materials. We observed the changes in release of the encapsulated TRITC-dextran molecules from the PAH/PSS microcapsules upon application of the 50 Hz alternating magnetic field. The obtained results open new horizons for the design of polymer systems for triggered drug release without dangerous heating and overheating of tissues.

Polyelectrolyte microcapsules have been prepared by successively adsorbing oppositely charged sodium polystyrenesulfonate and polyallylamine hydrochloride molecules on the surface of calcium carbonate colloid particles. Capsule shells have been functionalized using Fe₃O₄ magnetic nanoparticles to control the localization of microcapsules and penetrability of their shells. The penetrability control of microcapsules by means of a low-frequency nonheating magnetic field is based on magnetomechanical action, which is preferable to magnetic hyperthermia for in vivo applications because of its higher penetrability, locality, and safety. The influence of a pulsed low-frequency (50 Hz) sine-wave magnetic field on the microcapsule shell penetrability for fluorescently labeled dextran molecules has been analyzed. It has been found that the shell penetrability grows with decreasing time between magnetic field pulses, thereby increasing the dextran concentration in the shell.

The modification of capsule shells with synthesized magnetic iron oxide nanoparticles aims not only to control the localization of capsules, but also to tune their permeability. The application of a super low frequency non-heating magnetic field (100 Hz) for these purposes offers prospects for high penetration ability into tissues, high locality, and safety, which makes this method preferable for use with in vivo rather than magnetic hyperthermia. In this work, we develop a proof of concept for the remotely controlled release of an encapsulated drug from polyelectrolyte microcapsules under exposure to an alternating super low frequency magnetic field. The characteristics of the tailor-made nanoparticles for the polyelectrolyte shell modification were analyzed to confirm their perspectives as magneto-mechanical actuators due to their abilities with the Brownian relaxation. Polyelectrolyte microcapsules were obtained using the well-known method of sequential deposition of polyelectrolytes on the surface of vaterite particles. We studied the time dependence of the amount of released fluorescently labeled high-molecular weight substance on the frequency of the applied magnetic field (100 mT, 20–100 Hz) and demonstrated that the application of a magnetic field with a frequency of 50 Hz leads to the most pronounced selective increase in the permeability of the shells. Our findings provide a promising application of composite magnetic microcapsules with permeability triggered by a super low frequency magnetic field for the controlled release of drugs without dangerous heating or overheating of the biological tissues. This work was supported by the grant of the President of the Russian Federation (MK-1109.2021.1.3).

Polyelectrolyte microcapsules have been prepared by sequential adsorption of oppositely charged sodium polystyrene sulfonate and polyallylamine hydrochloride molecules on the surface of calcium carbonate particles. The capsule shells are functionalized with Fe3O4 magnetic nanoparticles to provide control over the localization of microcapsules and the permeability of their shells. The control of microcapsule permeability using a low-frequency non-heating magnetic field is based on the magneto-mechanical actuation, which, due to its high penetration ability, locality and safety, is preferable for application in vivo to magnetic hyperthermia. Here we report on the results of analysis of the effect of a low-frequency pulsed sinusoidal magnetic field with a frequency of 50 Hz on the permeability of the microcapsule shell for fluorescently labeled dextran molecules. It was found that the permeability of the shell increases with a decrease in the duration of the pause between magnetic field pulses, causing an increase in the amount of dextran in the shell.