Development of Technology for the Synthesis of Nanocrystalline Cerium Oxide Under Production Conditions with the Best Regenerative Activity and Biocompatibility for Further Creation of Wound-Healing Agents
Authors: Silina Ekaterina V. , Stupin Victor A. , Manturova Natalia E. , Chuvilina Elena L. , Gasanov Akhmedali A. , Ostrovskaya Anna A. , Andreeva Olga I. , Tabachkova Natalia Y. , Abakumov Maxim A. , Nikitin Aleksey A. , Kryukov Alexey A. , Dodonova Svetlana A. , Kochura Aleksey V. , Pugachevskii Maksim A. 
Published: October 2024

Background/Objectives: The issue of effective wound healing remains highly relevant. The objective of the study is to develop an optimal method for the synthesis of nanosized cerium oxide powder obtained via the thermal decomposition of cerium carbonate precipitated from aqueous nitrate solution for the technical creation of new drugs in production conditions; the select modification of synthesis under different conditions based on the evaluation of the physicochemical characteristics of the obtained material and its biological activity, and an evaluation of the broad-spectrum effect on cells involved in the regeneration of skin structure as well as antimicrobial properties. Methods: Several modes of the industrial synthesis of cerium dioxide nanoparticles (NPs) were carried out. The synthesis stages and the chemical and physical parameters of the obtained NPs were described using transmission electron microscopy (TEM), X-ray diffraction, Raman spectroscopy, and mass spectrometry. The cell cultures of human fibroblasts and keratinocytes were cultured with different concentrations of different nanoceria variations, and the cytotoxicity and the metabolic and proliferative activity were investigated. An MTT test and cell counting were performed. The antimicrobial activity of CeO2 variations at a concentration of 0.1–0.0001 M against Pseudomonas aeruginosa was studied. Results: The purity of the synthesized nanoceria powders in all the batches was >99.99%. According to TEM data, the size of the NPs varied from 1 nm to 70 nm under different conditions and methodologies. The most optimal technology for the synthesis of the nanoceria with the maximum biological effect was selected. A method for obtaining the most bioactive NPs of optimal size (up to 10 nm) was proposed. The repeatability of the results of the proposed method of nanoceria synthesis in terms of particle size was confirmed. It was proven that the more structural defects on the surface of the CeO2 crystal lattice, the higher the efficiency of the NPs due to oxygen vacancies. The strain provided the best redox activity and antioxidant properties of the nanoceria, which was demonstrated by better regenerative potential on various cell lines. The beneficial effect of synthesized nanoceria on the proliferative and metabolic activity of the cell lines involved in skin regeneration (human fibroblasts, human keratinocytes) was demonstrated. The antimicrobial effect of synthesized nanoceria on the culture of the most-resistant-to-modern-antibiotics microorganism Pseudomonas aeruginosa was confirmed. The optimal concentrations of the nanoceria to achieve the maximum biological effect were determined (10−3 M). Conclusions: It was possible to develop a method for the industrial synthesis of nanoceria, which can be used to produce drugs and medical devices containing CeO2 NPs.