Nanobiotechnology in Diagnosis, Drug Delivery and Treatment. Группа авторов

of SeNPs and other selenium drugs with the same dose of selenium.

      It was proposed that the inclusion of SeNPs in liposomes was a highly effective form of treatment for streptozotocin‐induced experimental diabetes. Liposomal forms of SeNPs made it possible to preserve the integrity of β‐cells of the pancreas followed by an increase in insulin secretion and, thus, led to reduction of blood glucose levels, suppression of oxidative stress, increase of antioxidant defense system, and inhibiting of pancreatic inflammation (Ahmed et al. 2017). Selenium nanocomposites loaded with mulberry leaf and Pueraria lobata extracts showed a slow phytomedicines release and good physiological stability in the simulated digestive fluid. These nanocomposites exert pronounced hypoglycemic effects in both normal and diabetic rats after oral administration. Ex vivo intestinal visualization showed that the nanocomposite had good permeability into the intestinal wall and the ability of transepithelial transport. It was also found that the composite improved the function of the pancreas and promoted glucose utilization by adipocytes (Deng et al. 2019).

      In recent years, SeNPs have commonly been used for the delivery of proteins and peptides. Proteins, being a kind of stabilizer, are often involved in the synthesis of SeNPs (Zhang et al. 2018). SeNPs was used for oral delivery of insulin. In this case insulin acts as a therapeutic agent and stabilizer of SeNPs and acquires the ability to avoid degradation by digestive enzymes in the gastrointestinal tract. The composite had intestinal permeability, and after oral administration it exerts significant hypoglycemic effect in both normal rats and rats with type 2 diabetes. The relative pharmacological bioavailability was up to 9.15% compared to subcutaneously injected insulin (Deng et al. 2017). SeNPs loaded with pituitary adenylate cyclase‐activating peptide resulted in increased insulin secretion and sustained hypoglycemic effect with an injection dose of 20 nmol l⁻¹ in mice with type 2 diabetes. Repeated administration for 12 weeks significantly improved glucose and lipids profile, insulin sensitivity, and histomorphology of pancreatic and adipose tissues (Zhao et al. 2017b). Therefore, diabetes treatment can be one of the potential applications for the use of selenium nanocomposites.

2.8 Other Applications of Nanoselenium

SeNPs coated with polysaccharides from Ulva lactuca were developed and investigated for their anti‐inflammatory efficacy in a model of acute colitis by Zhu et al. (2017). The treatment with SeNPs reduced body weight loss and inflammatory damage of the colon in mice and reduced infiltration with macrophages. It was shown that anti‐inflammatory effects of SeNPs were associated with a decrease in the level of pro‐inflammatory cytokines, in particular IL‐6 and tumor necrosis factor alpha (TNF‐α), by inhibiting the activation of macrophages through suppressing nuclear translocation of NF‐κB responsible for the transcription of these pro‐inflammatory cytokines (Zhu et al. 2017). Atteia et al. (2018) investigated and described the potential protective mechanism of SeNPs against lead acetate‐induced thyrotoxicity. It was found that SeNPs can prevent acetate‐induced hypothyroidism and oxidative damage in the tissues of the thyroid gland. SeNPs can also be used as effective drug carriers based on nucleic acids, and their use may be promising in gene therapy (Li et al. 2016).

      Ren et al. (2019) in a rat model of rheumatoid arthritis induced by Freund's adjuvant showed that SeNPs loaded with p‐Сoumaric acid are an effective therapeutic agent for inflammatory diseases. The data were confirmed by histological examination, the level of antioxidant enzyme activity, and inflammatory cytokines (TNF‐α, IL‐1β, IL‐6, and MCP‐1) (Ren et al. 2019). El‐Ghazaly et al. (2017) showed that nano‐Se has potential anti‐inflammatory activity against radiation‐induced inflammation in rats.

In another study, Nematollahi et al. (2018) in ex vivo experiments showed that SeNPs can play an important role in the treatment of hydatid cyst. Considering the significant biological role of selenium in the implementation of vital functions for the cell and in bone mineralization, Hoeg et al. (2012) studied the possibility of use of selenium in the form of nanoparticles in the polysaccharide arabinogalactan with local application to modify the reparative process for bone and muscle tissue injuries. The effect of elemental selenium/arabinogalactan nanocomposite (local introduction) on reparation of bone and muscular tissue in a trauma area has been studied. In animals, to which elemental selenium/arabinogalactan nanocomposite was introduced, the regeneration of bone tissue was absent in the fracture area. Bone trabeculars were destroyed. Activation of osteoclasts both in the area of new bone formation and in the area of old bone was observed (Figure 2.5). In this group of animals, the muscular tissue in the area adjacent to trauma zone was stained unevenly. Many fibers have lost cross‐striation. Necrosis of separate muscular fibers owing to infiltration with macrophages and lymphocytes was observed (Figure 2.6).

Figure 2.5 Regenerative process during fracture (a) The control group. Bone regenerates in the upper third of the perforated fracture of the tibia. Hematoxylin and eosin. (b) Experimental group. Lack of bone regeneration in perforated fracture. Hematoxylin and eosin. (c) Experimental group. Osteoclast activation in the area of the fracture. Hematoxylin and eosin.

Figure 2.6 The effect of the nanocomposite of elemental selenium and arabinogalactan on the repair of muscle tissue when administered locally for 35 days. (a) Experimental group: Loss of cross‐striations, disorientation of individual muscle fibers in the fracture zone. Hematoxylin and eosin. (b) Experimental group: Death of individual muscle fibers, infiltration of lymphocytes and macrophages in the area of the fracture. Hematoxylin and eosin.

      The electron microscope study of the muscular tissue from damaged area in animals after introduction of the selenium nanocomposite has shown that the muscular tissue is considerably changed compared to the control group. Areas of abnormal orientation of muscular fibers were revealed, Z‐lines were considerably curved, I‐bands were expanded, and contractile proteins were degradable. Nuclei of myocyte were of irregular shape with clearing zones. The biotesting data indicate that local application of the nanobiocomposite of elemental selenium in the reparation area at injury of bone and muscular tissue leads to a considerably impaired reparative process of both bone and muscular tissue. Impairments of osteoreparation are expressed in osteoresorption, and slowing of bone regeneration was also observed. In our opinion, significant damage to muscle fibers of a toxic nature is observed: loss of transverse striation of muscle fibers, death of some fibers, and infiltration by lymphocytes and macrophages.

2.9 Conclusion

Selenium nanocomposites are promising compounds with great potential for medicinal use. Nowadays, the main spectrum of beneficial use of these nanocomposites is associated with their use for the diagnosis and treatment of various diseases. In addition, these compounds can act as multifunctional platforms for targeted drug delivery and simultaneous detection of SeNPs in tissues due to their fluorescent ability. Prospects for the use of SeNPs are associated with the synergism of their antitumor activity and ability for target delivery of antitumor agents. Alzheimer's disease and diabetes are two