Modeling brain pathology to study nose-to-brain drug delivery.

OBJECTIVES: To create a new mucoadhesive dosage form based on PluronicF127 followed by transformation into a gel form upon intranasal administration for targeted delivery to brain tissueMETHODS: Citicoline, cytidine diphosphocholine, designated as CDP-choline, was purchased as a white powder with the molecular weight of 510.31 g/mol. The triblock copolymers of polyethylene glycol-block-polypropylene glycol-block-polyethylene glycol (PEG-PPG-PEG), branded as Pluronic F127, was used. RESULTS: When instilled into the nasal cavity, Pluronic F127 for intranasal administration is transformed into a gel that remains retained for 45-55 minutes, which promotes better penetration of drugs into the brain tissue. CONCLUSION: The polymer's gelling and adhesive properties performed well, which is crucial for further research at the preclinical stage (Tab. 1, Fig. 5, Ref. 28).

Biomarkers of immunothrombosis and polymorphisms of IL2, IL6, and IL10 genes as predictors of the severity of COVID-19 in a Kazakh population.

OBJECTIVES: To study the role of biological markers of immunothrombosis and polymorphisms of cytokine genes IL2, IL6, IL10 and their influence on the severity of COVID-19 in a Kazakh population. METHODS: A total of 301 patients of Kazakh nationality with a confirmed diagnosis of COVID-19 participated in the retrospective study, including 142 patients with severe and 159 with a mild course. Single nucleotide polymorphisms IL2R rs1801274, IL6 rs2069840, and IL10 rs1800872 were genotyped by real-time PCR. Activated partial thromboplastin time, normalized ratio, prothrombin index, prothrombin time, fibrinogen prothrombin time, fibrinogen, D-dimer, and C-reactive protein analysis were also conducted. RESULTS: The average age of patients with severe COVID-19 is higher than of patients with mild COVID-19 (p = 0.03). The findings showed that fibrinogen, D-dimer, and C-reactive protein were significantly greater in the group of patients with severe COVID-19 (p = 0.0001). A very strong correlation between the severity of COVID-19 with the D-dimer and C-reactive protein (p = 0.9) (p = 0.02) was found. CONCLUSION: The results of our study confirm that D-dimer, fibrinogen, and CRP are biomarkers of inflammation and hypercoagulation that serve as predictors of immunothrombosis affecting the severity of COVID-19. D-dimer is also associated with IL10 rs1800872 gene polymorphism in the Kazakh population with severe COVID-19.