Preparation and characterization of curcumin‐loaded polymeric nanomicelles to interference with amyloidogenesis through glycation method

Abstract

Amyloid fibrils, including β-amyloid (Aβ) fibrils, are protein aggregates that form under certain conditions, associated with neurodegeneration that interfere with neural synaptic transmission resulting in some neural disorders, such as Alzheimer's disease. The aim of this study is to inhibit amyloidogenesis by using preparatory polymeric nanomicelles as therapeutic agents and also as nanocarriers for curcumin to target Aβ fibrils through the glycation method of bovine serum albumin (BSA) in the presence of phosphate-buffered saline. Polymeric nanomicelles were prepared from phosphatidylethanolamine-distearoyl methoxypolyethylene glycol conjugates in the presence and absence of curcumin and then the morphological and structural characteristics of the nanomicelles were characterized in detail. Following the preparation of unloaded and curcumin-loaded nanomicelles with the desired size and properties, their effects on BSA glycation/fibrillation process were investigated. The samples were analyzed by thioflavin T (ThT) fluorescence and advanced glycation end (AGE) products autofluorescence measurements. The results showed that ThT fluorescence related to the formation of β-sheets and AGE autofluorescence (associated with AGE production) decreased in the presence of curcumin-loaded nanomicelles more than other samples. In conclusion, the promising effect of curcumin-loaded nanomicelles on inhibition of amyloidogenesis through glycation process due to curcumin release and thus their ability to prevent the formation and accumulation of amyloid fibrils and so to suppress the Alzheimer's disease progression has been proven and can go for further investigations.

Action Mechanisms of Curcumin in Alzheimer’s Disease and Its Brain Targeted Delivery

“…First, it has exceptionally low water solubility (11 ng/mL in aqueous buffer pH 5.0), which means that it is eliminated from the body quickly and has a low oral bioavailability. It is soluble in dichloromethane [ 61 , 62 ], ethyl acetate [ 63 , 64 ], ethanol [ 65 ], acetone [ 66 , 67 ], chloroform [ 68 ], dimethyl sulfoxide [ 69 ], and methanol [ 70 ]. Due to its low water solubility, it is eliminated from the body at a fast rate, and therefore, its oral bioavailability is quite low.…”

“…ii . β-amyloid content: thioflavin T (Tht) staining [ 61 , 76 , 77 , 78 , 79 ] silver staining [ 39 , 80 ], cresyl violet [ 81 ], alkaline phosphates [ 82 , 83 ], congo red [ 78 , 79 ], and ELISA assay [ 2 , 18 , 84 ]. iii .…”

Advances on Therapeutic Strategies for Alzheimer’s Disease: From Medicinal Plant to Nanotechnology

“…It was observed that this combination improved the long-term memories and also inhibited the level of Aβ plaques circulated [ 163 ]. The investigations showed that the combination of micelles with Tween-80 to obtain curcumin micelles increases the efficacy and availability of curcumin to treat AD symptoms [ 164 ]. In the recent studies, the impact of PEG ceramide nanomicelles was analyzed on neuronal N2 cells which showed the high efficacy of nanomicelles in mediating tau proteins’ degradation and inducing autophagy in targeted cells.…”

Curcumin as Prospective Anti-Aging Natural Compound: Focus on Brain

“…Moreover, it has been noted that curcumin-loaded nanomicelles suppressed the AD progression reducing protein fibrillation and inhibiting the amyloidogenesis through glycation process due to curcumin release, thus preventing the formation and accumulation of amyloid fibrils and glycation. This effect is also sustained by higher effectiveness of curcumin-loaded micelles due to their degradation or hydrolysis and subsequently the release of curcumin as an antioxidant agent [ 115 ].…”