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).

Discovery of Di(het)arylmethane and Dibenzoxanthene Derivatives as Potential Anticancer Agents.

A family of bifunctional dihetarylmethanes and dibenzoxanthenes is assembled via a reaction of acetals containing a 2-chloroacetamide moiety with phenols and related oxygen-containing heterocycles. These compounds demonstrated selective antitumor activity associated with the induction of cell apoptosis and inhibition of the process of glycolysis. In particular, bis(heteroaryl)methane containing two 4-hydroxy-6-methyl-2H-pyran-2-one moieties combine excellent in vitro antitumor efficacy with an IC50 of 1.7 µM in HuTu-80 human duodenal adenocarcinoma models with a high selectivity index of 73. Overall, this work highlights the therapeutic potential of dimeric compounds assembled from functionalized acetals and builds a starting point for the development of a new family of anticancer agents.

A Modern Approach to the Treatment of Traumatic Brain Injury.

Background: Traumatic brain injury manifests itself in various forms, ranging from mild impairment of consciousness to severe coma and death. Traumatic brain injury remains one of the leading causes of morbidity and mortality. Currently, there is no therapy to reverse the effects associated with traumatic brain injury. New neuroprotective treatments for severe traumatic brain injury have not achieved significant clinical success. Methods: A literature review was performed to summarize the recent interdisciplinary findings on management of traumatic brain injury from both clinical and experimental perspective. Results: In the present review, we discuss the concepts of traditional and new approaches to treatment of traumatic brain injury. The recent development of different drug delivery approaches to the central nervous system is also discussed. Conclusions: The management of traumatic brain injury could be aimed either at the pathological mechanisms initiating the secondary brain injury or alleviating the symptoms accompanying the injury. In many cases, however, the treatment should be complex and include a variety of medical interventions and combination therapy.

Prevention of Postoperative Urethral Strictures by Irrigation with 5-Fluorouracil via a Modified Urinary Catheter.

Background and Objectives: Urethral strictures are the most common complications after surgical treatments of benign prostatic hyperplasia (BPH). Despite various preventive measures, the search for medications with antiproliferative activity and the development of surgical procedures to prevent the development of urethral strictures are still relevant. We evaluated the preventive efficacy of 5-fluorouracil against urethral strictures in patients undergoing surgery for BPH. Materials and Methods: A non-randomized clinical trial including 246 male patients with an average age of 70.0 ± 8.0 years was conducted. The main study group included 124 patients who, in addition to the standard treatment, received lavage with a 5-fluorouracil solution (1000 mg/20 mL per 500 mL of 0.9% isotonic saline) using a modified three-way urethral catheter. The monitoring of clinical, laboratory, and instrumental parameters was carried out 10 days, 3 months, and 6 months after surgery. Results: The evaluation of severity for dysuria symptoms in patients using the IPSS scale throughout the entire follow-up period showed a statistically significant decrease in ischuria and stranguria, prolongation of the interval between urinations, a decrease in intermittent urination, urinary incontinence, and straining before urination in the main group in comparison with the control patients. The patients of both study groups noted an improvement in the quality of life. It was found statistically significant decrease in the maximum urinary flow rate in the main group (p < 0.001). In the control group, after three months, four cases of urethral strictures and stenosis were recorded; after six months, this rate reached nine cases (7.3%), while in the main group, only one patient with infravesical obstruction was found (0.8%) (χ2 = 3.855, p < 0.05). Conclusions: The results of our study could indicate the effectiveness of the antiproliferative drug 5-fluorouracil in combination with use of a modified catheter in relation to the development of postoperative urethral strictures.