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. 2025 Jun;42(6):947-959.
doi: 10.1007/s11095-025-03877-5. Epub 2025 Jun 9.

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

Tripti Halder  1   2 , Niyati Acharya  3
Affiliations

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

Tripti Halder et al. Pharm Res. 2025 Jun.

Abstract

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.

Keywords: Alzheimer’s; Cationic nanostructured lipid carrier; Immunohistochemistry; Myricetin; Sialic acid.

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Conflict of interest statement

Declarations. Ethics Approval and Consent to Participate: The animal experiments were previously approved by the Committee for the purpose of Control and Supervision of Experiments on Animals (CPCSEA) and the experimental protocol was approved by the Institutional Animal Ethical Committee (IAEC) protocol no: IP/PCOG/PHD/21/020 and IP/PCOG/PHD/23/040. Consent for Publication: Not applicable. Competing interests: No relevant financial or nonfinancial interests need to be disclosed by the authors.

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