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.

Composite microcapsules based on polyelectrolytes and nanoparticles of iron oxides are synthesized, and the release of encapsulated high-molecular dextran under the influence of a low-frequency alternating magnetic field due to the magnetomechanical actuation of nanoparticles in a polymer shell is investigated. As a result of the chemical condensation of ferrous and ferric iron, single-domain magnetic spherical Fe₃O₄ nanoparticles are synthesized and characterized by transmission electron microscopy, dynamic light scattering, powder X-ray diffraction, and Mössbauer spectroscopy. Polyelectrolyte microcapsules from polyallylamine hydrochloride and sodium polystyrene sulfonate are modified with magnetic nanoparticles due to electrostatic adsorption on an oppositely charged polyelectrolyte layer. Dextran, labeled with tetramethyl rhodamine-5-isothiocyanate (TRITC-dextran), is used as the model substance for encapsulation; it is incorporated into CaCO₃ particles (soluble cores for the formation of capsules) by coprecipitation. The capsule samples are examined by scanning electron microscopy, dynamic light scattering, and fluorescence confocal microscopy. The capsules are exposed to an alternating magnetic field with an amplitude of 100 mT and frequencies of 30–110 Hz. The content of labeled dextran in the shell of the microcapsules and the supernatant is determined using fluorimetry and fluorescence confocal microscopy. The duration of exposure and the frequency of the magnetic field, at which the maximum release of dextran from composite capsules is achieved, are established. Exposure to a low-frequency alternating magnetic field can lead to significant deformation of the shell of polyelectrolyte microcapsules modified with magnetic nanoparticles and successful release of the encapsulated substance.

A series of calcium carbonate particles with sizes of 500 ± 80 and 200 ± 90 nm were obtained using mass crystallization in aqueous salt solutions by varying the reaction conditions and adding glycerol or a combination of polyethylene glycol, polysorbat-80 and cell cultural medium to the reaction volume. Calcium carbonate nanoparticles of 50 ± 30 nm in diameter were synthesized within the pores of mesoporous silica particles with a subsequent etching out of the template material. A complete characterization of the particles was carried out using scanning and transmission electron microscopy, X-ray powder diffraction, and dynamic and electrophoretic light scattering. CaCO₃ particles were loaded with anticancer drugs, porphyrazine and doxorubicin, with an encapsulation efficiency of 2–5 and 4–11 wt.%, respectively. The spontaneous release at pH 7 reached 15%, and when the particles are dissolved at pH 4, the release was about 45% of the substance during the day, regardless of the encapsulated substance. Functionalization of the surface of calcium carbonate particles with a biocompatible Pluronic-folic acid conjugate did not affect the particle size distribution and aggregative stability for all three samples. The effect of coatings on the rate of internalization and accumulation of particles by cells expressing folic acid receptors was established. It was also shown that the internalization of 50 ± 30 nm particles was more active than other samples.

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).