Preparation of Protein Aerogel Particles for the Development of Innovative Drug Delivery Systems.

The research was oriented towards the preparation of aerogel particles based on egg white and whey protein isolate using various dispersion methods: dripping, spraying, and homogenization. Based on the results of analytical studies, the most appropriate samples were selected to obtain aerogels loaded with the drug. The results of the experimental research were used to study methods for obtaining nasal drug delivery systems based on aerogels. Protein aerogels were obtained by thermal gelation followed by supercritical drying. The obtained particles of protein aerogels have a specific surface area of up to 350 m2/g with a pore volume of up to 2.9 cm3/g, as well as a porosity of up to 95%. The results of experimental studies have shown that changing the dispersion method makes it possible to control the structural characteristics of protein aerogel particles. The results of the studies were applied to obtain innovative nasal drug delivery systems for the treatment of socially significant diseases. Analytical studies were conducted to determine the amount and state of adsorbed drugs in protein aerogel particles, as well as in vivo experiments on the distribution of clomipramine in blood plasma and brain tissue of rats to study the pharmacokinetics and bioavailability of the resulting drug-loaded protein aerogel.

Chitosan Aerogel Particles as Nasal Drug Delivery Systems.

The nasal drug delivery route has distinct advantages, such as high bioavailability, a rapid therapeutic effect, non-invasiveness, and ease of administration. This article presents the results of a study of the processes for obtaining chitosan aerogel particles that are promising as nasal or inhalation drug delivery systems. Obtaining chitosan aerogel particles includes the following steps: the preparation of a chitosan solution, gelation, solvent replacement, and supercritical drying. Particles of chitosan gels were obtained by spraying and homogenization. The produced chitosan aerogel particles had specific surface areas of up to 254 m2/g, pore volumes of up to 1.53 cm3/g, and porosities of up to 99%. The aerodynamic diameters of the obtained chitosan aerogel particles were calculated, the values of which ranged from 13 to 59 µm. According to the calculation results, a CS1 sample was used as a matrix for obtaining the pharmaceutical composition "chitosan aerogel-clomipramine". X-ray diffraction (XRD) analysis of the pharmaceutical composition determined the presence of clomipramine, predominantly in an amorphous form. Analysis of the high-performance liquid chromatography (HPLC) data showed that the mass loading of clomipramine was 35%. Experiments in vivo demonstrated the effectiveness of the pharmaceutical composition "chitosan aerogel-clomipramine" as carrier matrices for the targeted delivery of clomipramine by the "Nose-to-brain" mechanism of nasal administration. The maximum concentration of clomipramine in the frontal cortex and hippocampus was reached 30 min after administration.

Cellular Automata Modeling of Three-Dimensional Chitosan-Based Aerogels Fiberous Structures with Bezier Curves.

In this work, a cellular automata approach was investigated for modeling three-dimensional fibrous nanoporous aerogel structures. A model for the generation of fibrous structures using the Bezier curves is proposed. Experimental chitosan-based aerogel particles were obtained for which analytical studies of the structural characteristics were carried out. The data obtained were used to generate digital copies of chitosan-based aerogel structures and to assess the accuracy of the developed model. The obtained digital copies of chitosan-based aerogel structures will be used to create digital copies of aerogel structures with embedded active pharmaceutical ingredients (APIs) and further predict the release of APIs from these structures.

Extrusion-Based 3D Printing for Highly Porous Alginate Materials Production.

Three-dimensional (3D) printing is a promising technology for solving a wide range of problems: regenerative medicine, tissue engineering, chemistry, etc. One of the potential applications of additive technologies is the production of highly porous structures with complex geometries, while printing is carried out using gel-like materials. However, the implementation of precise gel printing is a difficult task due to the high requirements for "ink". In this paper, we propose the use of gel-like materials based on sodium alginate as "ink" for the implementation of the developed technology of extrusion-based 3D printing. Rheological studies were carried out for the developed alginate ink compositions. The optimal rheological properties are gel-like materials based on 2 wt% sodium alginate and 0.2 wt% calcium chloride. The 3D-printed structures with complex geometry were successfully dried using supercritical drying. The resulting aerogels have a high specific surface area (from 350 to 422 m2/g) and a high pore volume (from 3 to 3.78 cm3/g).

Investigation of Aerogel Production Processes: Solvent Exchange under High Pressure Combined with Supercritical Drying in One Apparatus.

This work aims to contribute to the theoretical and experimental research of supercritical processes for intensification and combination in one apparatus. Investigation is carried out to improve production technology of organic alginate aerogels. It is proposed within the investigation to carry out the solvent exchange stage, an important stage of organic aerogels production, under pressure in a carbon dioxide medium in the same apparatus used for supercritical drying. The phase behavior in the system "carbon dioxide-water-2-propanol", which arises during such a solvent exchange stage, is studied theoretically. An experimental study of the process of step-by-step solvent exchange under pressure was carried out through multiphase and homogeneous regions of the phase diagram of such a system. As a result, new highly efficient technology for the production of organic aerogels was proposed, which can be implemented by combining the two main stages of the process.

Chitosan-Based Aerogel Particles as Highly Effective Local Hemostatic Agents. Production Process and In Vivo Evaluations.

Chitosan aerogels with potential applications as effective local hemostatic agents were prepared using supercritical carbon dioxide drying to preserve the chitosan network structure featuring high internal surfaces and porosities of up to 300 m²/g and 98%, respectively. For the first time, hemostatic efficacy of chitosan-based aerogel particles was studied in vivo on a model of damage of a large vessel in the deep wound. Pigs were used as test animals. It was shown that primary hemostasis was achieved, there were no signs of rebleeding and aerogel particles were tightly fixed to the walls of the wound canal. A dense clot was formed inside the wound (at the femoral artery), which indicates stable hemostasis. This study demonstrated that chitosan-based aerogel particles have a high sorption capacity and are highly effective as local hemostatic agents which can be used to stop massive bleeding.

Experimental Investigation and CFD Modeling of Supercritical Adsorption Process.

The kinetics of the supercritical adsorption process was experimentally studied by the example of "ibuprofen-silica aerogel" composition obtainment at various parameters: Pressure 120-200 bar and temperature 40-60 °C. Computational Fluid Dynamics (CFD) model of the supercritical adsorption process in a high-pressure apparatus based on the provisions of continuum mechanics is proposed. Using supercritical adsorption process kinetics experimental data, the dependences of the effective diffusion coefficient of active substance in the aerogel, and the maximum amount of the adsorbed active substance into the aerogel on temperature and pressure are revealed. Adequacy of the proposed model is confirmed. The proposed mathematical model allows predicting the behavior of system (fields of velocity, temperature, pressure, composition, density, etc.) at each point of the studied medium. It makes possible to predict mass transport rate of the active substance inside the porous body depending on the geometry of the apparatus, structure of flow, temperature, and pressure.

Alginate-Based Aerogel Particles as Drug Delivery Systems: Investigation of the Supercritical Adsorption and In Vitro Evaluations.

The present work focuses on the preparation of alginate-based aerogels in the form of particles for their further study as potential drug delivery systems (solid dosage forms). The dripping method was used to prepare certain gel particles, and supercritical drying was used to obtain final alginate-based aerogel particles. Three model active substances (ketoprofen, nimesulide, loratadine) were impregnated into the obtained aerogels using the supercritical adsorption process. Using the method of X-ray analysis, it was shown that the in the obtained drug-loaded aerogels the corresponding active substances are in an amorphous state, and the stability of this state after six months of storage is confirmed. In vitro dissolution tests for obtained drug-loaded aerogels was performed. For each sample, an appropriate dissolution medium (with certain pH) was determined. In vitro investigations showed the increasing of the release rate for all model active substances. Time was required to release and dissolve 50% of the active drug from drug-loaded aerogels (T1/2), reduced in comparison with pure active drugs in crystalline form. Obtained results provide insight into the application of alginate-based aerogel particles as a drug delivery system to improve pharmacokinetic properties of certain active drugs.