Alexander Vilesov

Shear-induced solvent release from gel particles: application to drug–delivery systems

The behaviour of a swollen-in-water hydrogel particle and of a chitosan-alginate micro-capsule immersed in a silicon oil under shear is studied by the rheo-optical method. Both gel and capsule quantitatively behave in a same way. Shear stress leads to a solvent release from a particle and a further increase of shear stress induces the solvent detachment from the released areas. Particle deformation and solvent release are reversible: when stopping the shear, the particle recovers its initial shape and volume. But when some solvent is detached, it flows separately as would do low-viscosity droplets immersed in a high-viscosity matrix.

Triple-responsive inorganic–organic hybrid microcapsules as a biocompatible smart platform for the delivery of small molecules

We designed novel hybrid inorganic/organic capsules with unique physicochemical features enabling multimodal triggering by physical (UV light, ultrasound) and chemical (enzymatic treatment) stimuli. Notably, the UV- and ultrasound response was achieved by a synergetic combination of TiO2 and SiO2 nanostructures which were in situ deposited into the polymer shell of microcapsules during sol-gel synthesis. This results in the formation of a composite hybrid shell with enhanced mechanical stability. Such sol-gel modification reduces the permeability of the capsule shell to allow for small molecule encapsulation. At the same time, these hybrid capsules consist of degradable polypeptides and polysaccharides and can be decomposed in response to enzymatic reaction. Upon employing different modes of treatment (UV-light, ultrasound or enzymatic degradation) we can stimulate different mechanisms of cargo release at desired times. Importantly, such capsules have been shown to be non-cytotoxic and can be internalized into human mesenchymal stem cells (MSCs) and cervical cancer cell lines (HeLa) revealing intracellular degradation. This work demonstrates that our hybrid capsules possess a triple stimuli-responsive effect, which is of capital importance for the future design and application of multimodal responsive platforms to improve externally stimulated release of bioactive compounds and their healthcare performance.

Mesenchymal Stem Cell Magnetization: Magnetic Multilayer Microcapsule Uptake, Toxicity, Impact on Functional Properties, and Perspectives for Magnetic Delivery

Mesenchymal stem cells (MSCs) are widely used in cell therapy due to their convenience, multiline differentiation potential, reproducible protocols, and biological properties. The potential of MSCs to impregnate magnetic microcapsules and their possible influence on cell function and ability to response to magnetic field have been explored. Interestingly, the cells suspended in media show much higher ability in internalization of microcapsules, then MSCs adhere into the surface. There is no significant effect of microcapsules on cell toxicity compared with other cell line-capsule internalization reported in literature. Due to internalization of magnetic capsules by the cells, such cell engineering platform is responsive to external magnetic field, which allows to manipulate MSC migration. Magnetically sorted MSCs are capable to differentiation as confirmed by their conversion to adipogenic and osteogenic cells using standard protocols. There is a minor effect of capsule internalization on cell adhesion, though MSCs are still able to form spheroid made by dozen of thousand MSCs. This work demonstrates the potential of use of microcapsule impregnated MSCs to carry internalized micron-sized vesicles and being navigated with external magnetic signaling.

Two-level delivery systems for oral administration of peptides and proteins based on spore capsules of Lycopodium clavatum

Two-level delivery systems (DSs) for oral administration of therapeutic proteins and peptides were developed. The first level consists of outer walls of Lycopodium clavatum spores (sporopollenin exine capsules, SECs) with included target objects; the alginate microgranules serve as the second (outer) level. Alginate (a pH-dependent natural polymer) protects peptides from gastric acidity and enzyme exposure and provides slow release of target objects in an alkaline intestinal medium. Introducing ovomucoid (a peptidase inhibitor) into alginate coatings prevents enzymatic hydrolysis of peptide objects in the intestinal medium. The elemental composition of spores and SECs was controlled using energy-dispersion spectroscopy and combustion analysis; their morphology was visualized by SEM. The efficiencies of different methods of SEC loading were compared. It was demonstrated that the load value was controlled by molecular mass and the value of the isoelectric point of target objects. A comparison of peptide in vitro release profiles from DSs of various structures into simulated gastric and intestinal fluids was carried out. The mechanism of peptide release from two-level DSs was suggested. SECs were found in rat blood after intragastric administration of the two-level DSs. Time profiles of therapeutic peptide release were obtained in vivo.

New-types of apparatus for producing microcapsules and microgranules

Two types of simple compact apparatuses for microencapsulation and microgranulation have been developed. The vibration-type apparatus is a better fit for producing gel-like microgranules of 1.5-3.0 mm in diameter to be used in production of food (fodder) products and additives and microgranulated cell culture. The spray apparatus is fit for operation in two modes: drop-forming (particles of 100-500 microm in diameter) and spray modes (particles of 10-50 microm in diameter). The apparatus is most efficient when used in the mode of forming the particles directly in the medium of liquid nitrogen with successive lyophilic drying (without preliminary defrosting). It is used for microgranulating the live virus materials with their virulence being preserved.

Microencapsulated fire-extinguishing fluids and reactive fire-extinguishing composites formed on their basis

The application of microencapsulated liquid gasifiable fire-extinguishing agents as reactive filling compounds for fire-extinguishing composites is considered. A new process for microencapsulation of environmentally friendly fire-extinguishing agents possessing enhanced stability is designed. Novel composite materials are produced with these agents. The thermal-destruction processes of microcapsules containing liquid gasifiable fire-extinguishing agents of different compositions are considered. Laboratory and bench-mark firing tests of the materials are performed.

Alginate-containing systems for oral delivery of superoxide dismutase. Comparison of various configurations and their properties

Abstract The regularities of release of therapeutic antioxidant enzyme superoxide dismutase (SOD) from various alginate-based delivery systems (DS) into simulated gastric and intestinal fluids were determined. The following systems were used: Ca-alginate granules (AG) prepared by various methods, porous carbonate cores with multilayer polyelectrolyte coating as well as the new two-level DS (Ca-AG containing carbonate cores loaded with proteins). The influence of the method of granule preparation, composition of gelation bath and ionic composition of the simulated fluids on release profiles of the protein from different DS was revealed. SEM images demonstrated changes in DS structures in various simulated fluids. The correlation between these changes and in vitro protein release was shown. The comparison of enzymatic activity of SOD encapsulated in DS of various configurations (including the systems containing different peptidase inhibitors) was made. The efficiency of protection of SOD activity in simulated intestinal fluid with trypsin was demonstrated.

Novel microencapsulated liquid fire extinguishers with a nanomodified microcapsule shell

A new process has been developed for the microencapsulation of ecologically safe and highly effective fire extinguishers, including the perfluoroketone Novec 1230 (whose Russian analog is Khladon PFK-49), which has enhanced stability for use as a basic functional component in fire-extinguishing polymer materials. When Freons are microencapsulated via common methods, an intense loss of the liquid core of the microcapsule in the course of drying and storage via diffusion through the shell occurs. The stabilization effect was attained through modification of the microcapsule shell material via addition (at the stage of shell formation) of nanoparticles of the mineral layered filler montmorillonite. The processes of thermal degradation of the resulting microcapsules have been studied and a substantial improvement in stability (reduced permeability of the shell) and, hence, the possibility of their application has been shown. Laboratory fire tests of materials were performed, and the high effectiveness of fire extinguishment by microencapsulated perfluoroketone and the fire-extinguishing polymer material has been demonstrated.