Development and evaluation of multi-functionalized sialic acid conjugated asiatic acid nanoconstruct to mitigate cognitive deficits in Alzheimer's disease

Tripti Halder, Bijit Saha, Namdev Dhas, Sanjeev Acharya, Niyati Acharya

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Sialic acid (SA) serves a critical role in neuronal repair and cognitive functions. SA is a nine-carbon carboxylated sugar with a glycoconjugate cap that acts as a ligand and surface decoration with SA facilitates delivery to the target site. The present research aimed to develop SA surface modified AA nanostructured lipid carrier (NLCs) with carbodiimide conjugation method. Sterylamine, poloxamer 188 and tween 80 were used as surfactants and several characterization studies including, differential scanning calorimetry, fourier transform infrared spectroscopy and x-ray photon spectroscopy were analyzed. Further, in vitro, neuroprotective efficiency was evaluated in SH-SY5Y cells and hCMEC/D3 cells and found significant potential effects with the treatments of developed NLCs. Pharmacodynamics studies were also assessed in beta-amyloid-injected rats following quantification of Alzheimer's disease (AD) hallmarks like, Aβ(1–42), tau-protein, glycogen synthase kinase-3β levels, interleukin-6 and tumor necrosis factor-α for neuroinflammatory responses. Characterization studies revealed the conjugation on developed NLCs. The in vitro and in vivo results showed significant effects of SA decorated NLCs in reversing the damage by toxicant which was further characterized by the levels of neurotransmitters like acetylcholinesterase, butyrylcholinesterase. The results revealed significant (p <.05) refurbishment of cholinergic functions after 28 days of treatment of developed NLCs. These preclinical findings support the use of SA as a ligand to deliver the AA at targeted site as well as to mitigate the cognitive deficits in AD.

Original languageEnglish
Article numbere22146
JournalDrug Development Research
Volume85
Issue number1
DOIs
Publication statusPublished - 02-2024

All Science Journal Classification (ASJC) codes

  • Drug Discovery

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