Sialic acid conjugated cationic nanostructured lipid carriers loaded with natural bioactives for the management of Alzheimer s disease

Abstract

The present research aimed to design and evaluate Myricetin (MY) loaded nanostructured lipid newlinecarriers (MY-NLCs) to observe the enhancement of the bioavailability in the brain and newlinecognitive function in Alzheimer s. MY-NLCs were prepared and optimized using central newlinecomposite design (CCD). In-vitro MTT assay and cellular accumulation were evaluated in SH- newlineSY5Y neuroblastoma cells. Animals were i.p injected the MYS and MY-NLCs at a dose of 40 newlinemg/kg body weight and MY concentration in brain and plasma were analysed (n=3). Further, newlinethe pharmacodynamics studies were evaluated in the (Aand#946;1-42) induced Alzheimer s rat model newline(n=6) and cognitive performance was assessed using Morris water maze (MWM) test followed newlineby histological and neurotransmitters analyses in rats brain. The optimized MY-NLCs showed newline89.7±26.0 nm particle size, 80.81±10.39% entrapment efficiency, and 5.08±1.0% of drug newlineloading capacity. The in-vitro release studies revealed a biphasic release pattern and also newlinedemonstrated distinct cellular internalization in SH-SY5Y cells. Developed MY-NLCs newlineexhibited 2.77 folds higher AUC 0-24 in plasma and drug targeting efficiency for MY into the newlinebrain was found 127.05% as compared to MYS. The mitigating potential of MY-NLCs newline(10mg/kg) was also observed in behavioural parameters and neurotransmitter levels regulation newlinein the rat brain. MY-NLCs would be investigated as a potentially promising drug delivery newlineplatform for a variety of neurodegenerative payloads. newlineBased on preliminary successful findings, we further develop and evaluate cationic MY newlinefabricated nanostructured lipid carrier (Cat-MY-NLC) and sialic acid (SA) grafted Sia-Cat- newlineMY-NLC for Alzheimer s disease (AD) management. After characterization studies, In-vitro newlinecytotoxicity, cellular uptake, Aand#946; aggregation inhibition and mitochondrial membrane potential newlineof prepared NLCs were observed in SH-SY5Y cells. The trans- endothelial electrical resistance newline(TEER) was measured through HCMEC/D3 cells. Finally, the pharmacokinetic and newlinepharmacodynamic studies were also performed.