Purpose <p>The current study was conducted to develop and evaluate sialic acid grafted cationic myricetin (MY) fabricated nanostructured lipid carrier (Sia-Cat-MY-NLC) for Alzheimer’s disease (AD) management.</p> Methods <p><i>In-vitro</i> amyloid beta aggregation inhibition and mitochondrial membrane potential of prepared NLCs were observed in SH-SY5Y cells. The transendothelial electrical resistance was measured through hCMEC/D3 cells. Pharmacokinetic and pharmacodynamic studies were conducted to evaluate neuropharmacokinetic parameters and levels of AD hallmarks in AD rats.</p> Results <p>The optimized formulations showed particle sizes (142.26 ± 24.16&#xa0;nm and 236.3 ± 15.26&#xa0;nm), zeta potentials (36.5 ± 2.43 mv and -2.4 ± 1.30 mv) respectively for Cat-MY-NLC and Sia-Cat-MY-NLC. Prepared NLCs treatments revealed significant neuroprotective effects in SH-SY5Y cells followed by the ability to cross the <i>in-vitro</i> BBB model. Results of pharmacokinetic studies showed 5.3 and 5.88 folds enhanced bioavailability with Cat-MY-NLC and Sia-Cat-MY-NLC administration respectively.</p> Conclusions <p>The results of enzymatic analysis showed a significant (<i>p</i> &lt; 0.05) restoration of AD hallmark levels in the brain after Sia-Cat-MY-NLC treatment than Cat-MY-NLC.</p> Graphical Abstract <p></p>

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Sialic Acid-based Glycoconjugation on Myricetin-encapsulated Cationic Nanocarriers for the Treatment of Alzheimer's

  • Tripti Halder,
  • Niyati Acharya

摘要

Purpose

The current study was conducted to develop and evaluate sialic acid grafted cationic myricetin (MY) fabricated nanostructured lipid carrier (Sia-Cat-MY-NLC) for Alzheimer’s disease (AD) management.

Methods

In-vitro amyloid beta aggregation inhibition and mitochondrial membrane potential of prepared NLCs were observed in SH-SY5Y cells. The transendothelial electrical resistance was measured through hCMEC/D3 cells. Pharmacokinetic and pharmacodynamic studies were conducted to evaluate neuropharmacokinetic parameters and levels of AD hallmarks in AD rats.

Results

The optimized formulations showed particle sizes (142.26 ± 24.16 nm and 236.3 ± 15.26 nm), zeta potentials (36.5 ± 2.43 mv and -2.4 ± 1.30 mv) respectively for Cat-MY-NLC and Sia-Cat-MY-NLC. Prepared NLCs treatments revealed significant neuroprotective effects in SH-SY5Y cells followed by the ability to cross the in-vitro BBB model. Results of pharmacokinetic studies showed 5.3 and 5.88 folds enhanced bioavailability with Cat-MY-NLC and Sia-Cat-MY-NLC administration respectively.

Conclusions

The results of enzymatic analysis showed a significant (p < 0.05) restoration of AD hallmark levels in the brain after Sia-Cat-MY-NLC treatment than Cat-MY-NLC.

Graphical Abstract