In a paper published in the journal Pharmaceuticals, researchers developed metformin carbon quantum dots (MetCQDs) to improve Met’s bioavailability and efficacy for type II diabetes. MetCQDs, created using a microwave method, showed promising particle stability and effectiveness in lowering blood sugar in diabetic rats, achieving significant reductions compared to Met alone. Histopathological analysis indicated improved liver health in the MetCQD-treated group, suggesting potential therapeutic benefits with reduced side effects.
Study: Oral Active Carbon Quantum Dots for Diabetes. Image Credit: Leo Matyushkin/Shutterstock.com
Related Work
Past work has shown that Met, a biguanide class antidiabetic agent, inhibits liver gluconeogenesis and enhances insulin-mediated glucose uptake, making it effective for type II diabetes. Despite Met's benefits, CQDs have drawn interest for drug delivery due to their stability, low toxicity, and ease of synthesis. However, the challenge lies in improving Met's bioavailability while minimizing dosing frequency and side effects.
MetCQDs: Methodological Insights
This study employed various materials and methods for synthesizing and evaluating MetCQDs. Citric acid monohydrate and polyethylene glycol 3350 (PEG 3350) were sourced from Sigma Aldrich, while SANOVEL provided Met hydrochloric acid (HCl). A microwave reactor enabled the one-step synthesis of MetCQDs, characterized using particle size analysis, zeta potential, and spectrofluorometric properties. In vivo experiments involved Wistar albino rats sourced from the Kobay Animal Study Center in Ankara, adhering to ethical guidelines from the Ankara University Faculty of Pharmacy. Diabetes was induced in the rats with streptozotocin (STZ), and blood glucose levels were assessed using a Bayer Glucometer Elite.
The MetCQD synthesis process involved optimizing parameters affecting particle dimensions and surface characteristics. Citric acid acted as the carbon source, while Met was the active pharmaceutical ingredient. The solutions were heated at 160 °C for 20 minutes in a microwave reactor before cooling to ambient temperature. Surface modification was completed by adding PEG 3350 to enhance stability.
Characterization included particle morphology analysis using a transmission electron microscope (TEM), particle size distribution via LiteSizer 500, and optical properties assessment with a spectrofluorometer. Quantum yield calculations were performed using a comparative method with quinine sulfate based on fluorescence intensity over various dilution levels.
Animal testing involved administering Met or MetCQD formulations to STZ-induced diabetic rats, with blood glucose monitored over intervals. Rats underwent an oral glucose tolerance test (OGTT) and fasting blood glucose measurement before and after MetCQD administration.
The study utilized four groups: a control, a diabetic control, a Met-treated group, and a MetCQD-treated group, ensuring an accurate comparison of each treatment's effectiveness. The animals were compassionately euthanized following the testing phase, and the pancreatic and liver tissues were obtained for histopathological assessment.
Histopathological assessments involved staining tissue sections with hematoxylin and eosin and microscopic evaluation of pancreatic islets and liver cells. The tissues were examined for atrophic changes in pancreatic islets and necrotic or degenerative alterations in liver cells, categorized on a scale ranging from mild to severe. Statistical analysis was conducted using a statistical package for the social sciences (SPSS), employing the Kruskal–Wallis test to detect significant differences between the groups and the Mann–Whitney U test to clarify specific group comparisons. A p-value of less than 0.05 was regarded as evidence of statistical significance.
Production and Benefits of MetCQDs
MetCQDs were successfully synthesized through a straightforward and easily applicable one-step production method. A total of 0.2 g of citric acid monohydrate was utilized as a carbon source, combined with 0.5 g of Met, serving as both a heteroatom and an active pharmaceutical ingredient. The synthesis was cost-effective and rapid, resulting in a blue-green fluorescent emission under UV light at 365 nm, confirming successful completion. The physical properties of the MetCQDs were analyzed using techniques such as TEM, which indicated that the particles measured less than 10 nm, and a fluorescence spectrophotometer, which verified optimal emissions.
The characterization of MetCQDs extended to their quantum yield and stability. Using quinine sulfate as a standard, the calculated quantum yield of the MetCQDs was 80.3%. Stability tests revealed that the particle size, distribution, and zeta potential remained consistent across varying temperatures and humidity levels, with a calculated shelf life of over two years.
In vivo experiments confirmed the efficacy of MetCQDs in lowering blood glucose levels in Wistar albino rats, demonstrating a stronger hypoglycemic effect than Met. Blood glucose levels were effectively monitored, revealing significant decreases post-administration of the test materials. Treatment with MetCQDs and Met resulted in regeneration and improvements in both pancreatic and liver tissues, highlighting their potential therapeutic effects.
Conclusion
To sum up, MetCQDs were prepared using citric acid as a carbon source, with Met utilized for dual-action as a heteroatom and active molecule for the first time. The formulations demonstrated a hypoglycemic effect and a reduction in liver fat. This study highlighted that quantum dot formulations of active substances could pave the way for new treatment alternatives utilizing drug molecules in both roles. Further studies were deemed necessary to assess potential long-term effects.
Journal Reference
Camlik, G., et al. (2024). Oral Active Carbon Quantum Dots for Diabetes. Pharmaceuticals, 17:10, 1395. DOI: 10.3390/ph17101395, https://www.mdpi.com/1424-8247/17/10/1395
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