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• W3136350349 endingPage "120482" @default.
• W3136350349 startingPage "120482" @default.
• W3136350349 abstract "Numerous oral treatment options have been reported for neurological disorders, especially Alzheimer’s disease (AD). Galantamine (GAL) is one of such drugs duly approved for management of AD. However, it exhibits poor brain penetration, low intestinal permeation and requires frequent dosing in AD treatment. The present studies, accordingly, were undertaken to develop DSPE-PEG 2000-based micelles loaded with GAL for efficient brain uptake, improved and extended pharmacokinetics, along with reduced dosing regimen. Mixed nanomicelles (MNMs) were systematically formulated using QbD approach, and characterized for morphology, entrapment efficiency and in vitro drug release. Studies on CaCo-2 and neuronal U-87 cell lines exhibited substantial enhancement in the cellular permeability and uptake of the developed MNMs. Pharmacokinetic studies performed on rats showed significantly improved values of plasma AUC (i.e., 2.28-fold, p < 0.001), ostensibly due to bypassing of hepatic first-pass metabolism and improved intestinal permeability, together with significant rise in MRT (2.08-fold, p < 0.001) and tmax (4.80-fold; p < 0.001) values, indicating immense potential for prolonged drug residence in body. Besides, substantial elevation in brain drug levels, distinctly improved levels of biochemical parameters in brain homogenates and cognitive improvement in β-amyloid-treated rats, testify the superiority in MNMs in therapeutic management of AD. The preclinical findings of the developed nanocarrier systems successfully demonstrate the notable potential of enhanced drug efficacy, extended duration of action and improved patient compliance." @default.
• W3136350349 created "2021-03-29" @default.
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• W3136350349 date "2021-05-01" @default.
• W3136350349 modified "2023-10-13" @default.
• W3136350349 title "QbD-steered development of mixed nanomicelles of galantamine: Demonstration of enhanced brain uptake, prolonged systemic retention and improved biopharmaceutical attributes" @default.
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• W3136350349 doi "https://doi.org/10.1016/j.ijpharm.2021.120482" @default.
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• W3136350349 hasPublicationYear "2021" @default.
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