The Tragedy of Alzheimer’s Disease: Towards Better Management via Resveratrol-Loaded Oral Bilosomes

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disease where oxidative stress plays a major role as a key pathologic factor. The study aims to develop resveratrol (RES)-loaded bilosomes for oral use, aiming to enhance RES bioavailability. RES-loaded bilosomes were prepared using the thin-film hydration technique. The effect of different formulation variables viz. the number of extrusion cycles, drug concentration and the effect of pH of the medium and cholesterol addition on the physicochemical properties of the prepared bilosomes was investigated. Results revealed the successful entrapment of RES into bilosomes. An optimized formula was selected, showing the lowest particle size (189 ± 2.14), acceptable PDI (0.116) and entrapment efficiency (76.2 ± 1.36). In vivo studies on a streptozotocin-induced animal model of AD showed the preeminence of bilosomes over traditional drug suspension to enhance mice memory via Y-maze and Morris water maze tests. Moreover, mice treated with the optimized formula exhibited decreased COX2, IL-6, amyloid-beta peptide and Tau protein levels compared to the drug suspension. Immuno-histochemical analysis revealed a significant decrease of glial fibrillary acidic protein values and microglial cell count in mice treated with bilosomes. Finally, it could be advocated that RES-loaded bilosomes could be a promising drug delivery system to control AD.

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“…Followed by incubation with anti Bcl2: PA5–11379 (Thermo Fisher Scientific Co.) Anti-Glial Fibrillary Acidic Protein (GFAP), by using a monoclonal antibody kit (Cat. No.13–0300-Thermo-scientific Co. Waltham, MA, USA) 1:100 overnight at 4C; washing followed by incubation with secondary antibody HRP Envision kit (DAKO) 20 mins; washing by PBS (phosphate buffer saline) and incubated with 3,3 diaminobenzidine (DAB) for 10 mins, then cover slipped for microscopic examination [ 42 ].…”

“…Six non-overlapping fields were randomly scanned per tissue section of each sample for the determination of the relative area percentage of immunohistochemical expression levels of Bcl2 and GFAP in the cerebral cortex of different groups. Morphological measurements and analyzed data were obtained using Leica Application module for tissue section analysis attached to a Full HD microscopic imaging system (Leica Microsystems GmbH, Germany) [ 42 ].…”

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“…Another set of tissue sections was stained by Toluidine blue stain for the quantification of intact neurons, then inspected with light microscope. Standard protocols for sample preparation, staining, and analysis were followed according to Abbas, Culling and Abbas [ 81 , 82 , 83 ].…”