Effectivity of Rutin-bound Carbon dots in preventing the aggregation of Amyloid beta

Abstract

According to the World Health Organization up to 55 million people have dementia resulting in concerning socio-economic implications. About 60-80% cases of dementia are associated with Alzheimer's disease. With all the advances in medicine, there still is no cure. Blood-brain barrier monitors the entry and exit of nutrients and molecules which makes it difficult for various drugs and therapeutic molecules to cross it. Carbon dots are made from glucose to overcome the BBB. Rutin is a naturally existing flavonoid extracted from plants and has therapeutic effects in neuroprotection. This study aims to improve the effectiveness of rutin combined with targeted delivery of carbon dots. Carbon dots were loaded with Rutin to make CD-Rutin, a nano-sized combination with a targeted drug. FTIR, UV-IR, and SEM analysis have produced positive results regarding the doping of CDs with Rutin. Administration of CD-Rutin was done in AD-like rat models at eight to twelve months of age. Alzheimer's was induced in rats with Aluminum Chloride and D-galactose through IP administration for two weeks. Behavioral tests were performed to check the progression of the disease. In silico analysis was also done to check ligand-protein interaction to check variation in the binding of Aβ isoforms with Rutin. Afterward, a single injection of CD-Rutin (10 mg/kg) was given intraperitoneally as well. Behavioral testing was done after the administration of the drug. Characterization techniques revealed the successful formation of CDs and subsequent loading of Rutin onto the CDs resulting in a CD-Rutin combination. In silico analysis provided strong binding affinities of Rutin with Aβ isoforms affirming Rutin as a favorable treatment to target amyloid aggregates. 3D configuration showed binding of Rutin with hydrophobic domains of protein oligomers Behavioral testing provided significant difference in the treated group with better memory retention and performance in activities involved in behavioral testing. After behavioral testing, rats were dissected for molecular analysis including H&E to assess cell degeneration and Thioflavin T staining to assess amyloid aggregates in the brain tissues. Results provided positive data in terms of cell count in the cortex. Overall results suggest that memory impairment and cognitive abilities were significantly improved after injections. The results demonstrate the positive therapeutic potential of CD-Rutin in Alzheimer's treatment.