The layer-by-layer adsorption of polyethyleneimine and dextran sulfate onto the nanoparticles of biodegradable poly(D,L-lactide-co-glycolide) was conducted to produce potential delivery system of cyanocobalamin. The modified poly(D,L-lactide-co-glycolide) particles are found to be colloidal stable, nanosized with the value of hydrodynamic diameter of 210 nm and polydispersity index of 0.22. It was established that the content of cyanocobalamin absorbed by polyelectrolyte shell of the modified particles was 16 wt.

AIM:To develop polyelectrolyte multilayer capsules (PMC) loaded with doxorubicin (DOX) and modified with the DR5-B protein to overcome drug resistance in MCF-7 breast cancer cells. METHODS:The capsules were prepared by layer-by-layer (LbL) assembly followed by thermal shrinking, DOX encapsulation and DR5-B surface modification. The capsules were characterised using scanning electron microscopy (SEM), dynamic light scattering (DLS), and UV-Vis spectrophotometry. Cellular uptake was assessed by confocal microscopy, flow cytometry, and fluorimetry. Cytotoxicity was evaluated by MTT-test in 2D and 3D in vitro models. RESULTS:Mean capsule size was 320 ± 90 nm (PDI 0.39), mean ζ-potential was +29 ± 5 mV. The encapsulation efficiencies (ЕЕ) of DOX and DR5-B were 85 ± 7% and 80 ± 4%, with loading capacities (LC) of 9 ± 2 w/w% and 145 ± 40 w/w%, respectively. Shrunken capsules exhibited 3.5-fold higher internalisation than non-shrunken ones. DR5-B increased capsule accumulation by 1.8-fold. The capsules showed synergistic cytotoxicity in DR5-B-resistant MCF-7 spheroids (IC50 227 ± 13 ng/mL), being non-toxic to fibroblasts.

The development of smart photochromic materials, as the materials of the future, is of paramount importance with a wide range of applicability. Active research into photochromic materials began at the end of the last century and has not lost its relevance. The surrounding plays an important role in the manifestation of photochromism. The perspective strategy in this field is the encapsulation of the photochromic dyes in the system based on polymer shells. Encapsulation allows to optimize the kinetic properties of the photochromic molecule, to eliminate the problem of dye migration in the material matrix with loss of activity, to protect the photochromic compound from the harmful environmental factors and therefore to improve the fatigue resistance. Encapsulation could also provide a homogenous distribution of the encapsulated photoactive molecule within the smart material. Photochromes can be incorporated as part of the core of the capsule and can also as part of the polymeric shell that provides the photoswitching capability. The present review is devoted to a brief and conclusive analysis of the latest results on the encapsulation of the photochromic organic compounds from the classes of spiropyrans, spirooxazines and azobenzene derivatives in the polymer capsules. The appropriate application of each system is discussed along with characterization and property analysis. The trends in the development of the photochromic capsules are concluded.

Recently, we have described the first supermolecular nanoentities of vitamin B-12 derivative, viz. monocyano form of heptabutyl cobyrinate, unique nanoparticles with strong noncovalent intermolecular interactions, emerging optical and catalytic properties. Their nearest analogue, heptamethyl cobyrinate (ACCby), exhibits bioactivity. Here, we demonstrate the first example of the formation of nanoparticles of this nucleotide-free analogue of vitamin B-12 in protein nanocarriers and neuroprotective activity in vivo of the own nanoform of the drug. The preparation and characterization of nanocarriers based on bovine serum albumin (BSA) loaded with vitamin B-12 (viz. cyano- and aquacobalamins) and ACCby were performed. Nucleotide-free analogue of vitamin B-12 is tightly retained by the protein structure and exists in an incorporated state in the form of nanoparticles. The effect of encapsulated drugs on the character and severity of primary generalized seizures in rats induced by the pharmacotoxicant thiosemicarbazide was studied. Cyanocobalamin and ACCby exhibited a neuroprotective effect. The best influence of the encapsulation on the effectiveness of the drugs was achieved in the case of A & Scy;Cby, whose bioavailability as a neuroprotector did not change upon introduction in BSA particles, i.e., 33 % of surviving animals were observed upon ACCby administration in free form and in encapsulated state. No surviving rats were observed without the administration of drugs. Thus, BSA nanocarriers loaded by nanoparticles of nucleotide-free analogues of vitamin B-12,B- including hydrophobic ones, can be recommended for neuroprotection and targeted delivery.

New insights into the unique biochemical properties of riboflavin (Rf), also known as vitamin B2, are leading to the development of its use not only as a vitamin supplement but also as a potential anti-inflammatory, immunomodulatory, antioxidant, anticancer, and antiviral agent, where it may play a role as an inhibitor of viral proteinases. At the same time, the comparison of the pharmacoactivity of Rf with its known metabolites, namely, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), is very complicated due to its poor water solubility: 0.1-0.3 g/L versus 67 g/L for FMN and 50 g/L for FAD, which is the limiting factor for its administration in clinical practice. In this study, we report the recrystallization procedure of the type A Rf crystals into the slightly hydrophobic type B/C and a new hydrophilic crystal form that has been termed the P type. Our method of Rf crystal modification based on recrystallization from dilute alkaline solution provides an unprecedented extremely high water solubility of Rf, reaching 23.5 g/L. A comprehensive study of the physicochemical properties of type P riboflavin showed increased photodynamic therapeutic activity compared to the known types A and B/C against clinical isolates of Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Salmonella typhimurium. Importantly, our work not only demonstrates a simple and inexpensive method for the synthesis of riboflavin with high solubility, which should lead to increased bioactivity, but also opens up opportunities for improving both known and new therapeutic applications of vitamin B2.

The stabilization of Pickering emulsions with mixtures of similarly or oppositely charged detonation nanodiamonds and silica nanoparticles has been studied. Dynamic light scattering has been employed to study the influence of pH and the mass ratio of the particles on the sizes and ζ-potentials of aggregates. The formation of heteroaggregates from mixtures of similarly charged nanoparticles and the efficient stabilization of dodecane droplets have been shown and theoretically substantiated. Submicron droplets of Pickering emulsion stabilized with the mixtures of oppositely charged silica nanoparticles and detonation nanodiamonds have been obtained.

The calcium-carbonate-induced mineralization of multilayer shells of emulsion capsules, formed using layer-by-layer assembly of polyelectrolytes, has been investigated. Optimal conditions for forming microcapsules with a core from shea butter and an organic–inorganic shell from synthetic polyelectrolytes and calcium carbonate are found. The shell morphology and stability of capsules in an aqueous suspension upon heating are investigated, and their cytotoxicity for human fibroblast cells is estimated. It is shown that mineralization of emulsion polyelectrolyte capsules by calcium carbonate in the form of vaterite strengthens the capsule walls and increases their biocompatibility.

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.

In this review, the principles of the formation of polyelectrolyte microcapsules by the layer-by-layer assembly method have been considered, the intermolecular interactions that take part in the systems have been described, and the factors that affect the parameters of the resulting structures have been listed. Works devoted to tuning the internal structure of polyelectrolyte shells by means of variations in environmental conditions have been presented, in particular, the effect of temperature on polyelectrolyte shells of various compositions has been considered. Examples of changing the permeability of the shells, as well as imparting desired optical properties to the capsules by incorporating dyes and nanoparticles into polyelectrolyte multilayers have been presented. Possible approaches to remote control of shell permeability under the action of external physical stimuli, such as laser and microwave radiations and a low-frequency magnetic field, have been described. One of the sections of the review has been devoted to the methods of encapsulating emulsion droplets via layer-by-layer deposition of polyelectrolytes.

Capsules with shells based on nanoparticles of different nature co-assembled at the interface of liquid phases of emulsion are promising carriers of lipophilic drugs. To obtain such capsules, theoretically using the Derjaguin–Landau–Verwey–Overbeek (DLVO) theory and experimentally using dynamic light-scattering (DLS) and transmission electron microscopy (TEM) methods, the interaction of like-charged silica nanoparticles and detonation nanodiamonds in an aqueous solution was studied and their ratios selected for the formation of submicron-sized colloidosomes. The resulting colloidosomes were modified with additional layers of nanoparticles and polyelectrolytes, applying LbL technology. As a model anti-cancer drug, thymoquinone was loaded into the developed capsules, demonstrating a significant delay of the release as a result of colloidosome surface modification. Fluorescence flow cytometry and confocal laser scanning microscopy showed efficient internalization of the capsules by MCF7 cancer cells. The obtained results demonstrated a high potential for nanomedicine application in the field of the drug-delivery system development.

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).

Microcapsules are ideal cargo platform for variety of applications such as drug delivery, sensing and imaging due to the combination of a simplicity fabrication and flexibility in the design. We developed remotely collapsing polymer capsules to response to external microwave treatment. The multilayer structure of the capsules was designed to create a polyfunctional system intercalating with nanodiamonds (NDs) and upconversion nanoparticles (UCNPs) into the polyelectrolyte shell. NDs empower local overheating to the microcapsules, while UCNPs provide opportunity to luminescent thermal sensing. UCNPs consist of inorganic crystalline host matrix - hexagonal β-phase NaYF4, doped with pairs of trivalent lanthanide ions, which play role of sensitizer (Yb3+) and activator (Er3+). The microwave triggering followed by the capsule heating results in the controlled destruction of the polyelectrolyte shell with subsequent cargo release. UCNPs luminescence was utilized to determine the local temperature of the capsule shell at nanoscale under GHz ultrasonic treatment. Our novel approach provides on demand microcapsule system destruction, which can be used in the development of nanotheranostic platform for the unification of diagnosis and treatment of various diseases.

Background: Currently, different approaches of active and passive targeted drug delivery are being developed. One of the most promising methods of targeted drug delivery is the use of capsules. For instance, colloidosomes—capsules consisting of the shell formed by colloidal particles at the interface of the emulsion—can be used for targeted delivery of antitumor drugs or any other drugs in liquid form. Here we present results of cryo-EM study of submicrocapsules with the soybean oil core and with the shell consisting of SiO2 nanoparticles and detonation nanodiamonds (DNDs) stabilized with chitosan and alginate. Methods: Сryo-electron tomography (Cryo-ET) was used to identify the morphological features of the submicrocapsules. Preliminary screening of samples and cryo-ET data collection were performed using Titan Krios cryo-EM (ThermoFisher Scientific, US) equipped with Falcon 2 direct electron detector. The restoration of the tomographic series was carried out using IMOD software. Eman2 was used for segmentation and UCSF Chimera was used for visualization of the 3D model. Submicron capsules were obtained by stabilizing oil droplets with a mixture of SiO2 nanoparticles and DNDs. To form a stable shell, an additional layer of silica particles and polyelectrolyte layers of alginate/chitosan were applied to the droplets of the dispersed phase of the emulsion by physical adsorption. Results: Cryo-EM data showed the presence of submicrocapsules with a diameter in the range of 200-900 nm. Although a significant fraction of submicrocapsules was found to be partially destroyed, results of cryo-ET study of intact capsules demonstrated that silicon dioxide nanoparticles form a net, while DNDs form clusters. Conclusion: Here we demonstrate the results of the study of submicron capsules with a shell of silica nanoparticles and DNDs. It was found that a uniform distribution of DNDs is not a prerequisite for the creation of submicron capsules that contradicts the theoretical model.

The photochromic compounds are of great interest due to their unique ability to undergo reversible intramolecular transformations under the influence of light, accompanied by changes in the absorption spectrum. The aim of the present work is the development of the polymer system for encapsulation of the photochromic compounds with maintaining the photochromic properties. The core-shell capsules were produced by a versatile one-step ultrasound treatment. The capsules possess positive or negative photochromic effects depending on the nature of the photochromic systems to be encapsulated. The capsules are demonstrated a noticeable photochromic reaction, which could find a broad application in various fields including information and biomedical technologies.