Aurothioglucose encapsulated nanoparticles fostered neuroprotection in streptozotocin-induced Alzheimer's disease

Brain Res. 2024 Jul 1:1834:148906. doi: 10.1016/j.brainres.2024.148906. Epub 2024 Apr 1.

Abstract

Alzherimer's disease (AD) is an age-dependent ubiquitous ailment worldwide with limited therapies that only alleviate the symptoms of AD but do not cure them entirely because of the restricted blood-brain barrier passage of the drug. Hence with new advanced technology, nanoparticles can offer an opportunity as the active candidate to overcome the above limitations. Aurothioglucose, a synthetic glucose derivative of the gold compound, has been clinically proven to be an effective anti-inflammatory drug for rheumatic arthritis. Recently, several scientific groups have developed gold nanoparticle preparations and tested them for the treatment of dementia. This study was planned to prepare the PLGA nanoparticles of aurothioglucose (ATG) and check the neuroprotective potential against STZ-induced AD in rats. The nanoparticles were prepared using the double emulsion solvent evaporation method and characterized for various parameters such as drug-excipient interaction, particle size, zeta potential, and morphology. Then, rats were injected STZ (3 mg/kg/i.c.v., days 1 and 3) and ATG (5 and 10 mg/kg/s.c.), ATG NPs (2.5 and 5 mg/kg/s.c.) and donepezil (2 mg/kg/p.o) from 15th to 29th day. Behavior parameters were performed using an actophotometer, MWM, and ORT. On the 30th day, all the animals were sacrificed, and the brains were isolated for estimating biochemical, neurochemical, and proinflammatory markers. It was observed that ATG NPs significantly restored all behavior and neurotransmitter alterations caused by STZ. Also, it increased antioxidant levels and decreased inflammatory cytokines significantly, then ATG alone. Thus, the study suggests that ATG loaded PLGA NPs could be used as a novel therapeutic strategy to slow the process of AD.

Keywords: Alzheimer’s disease; Aurothioglucose; Nanoparticles; Neuroinflammation; PLGA; Streptozotocin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease* / drug therapy
  • Alzheimer Disease* / metabolism
  • Alzheimer Disease* / pathology
  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Disease Models, Animal
  • Male
  • Nanoparticles* / administration & dosage
  • Neuroprotection / drug effects
  • Neuroprotective Agents* / pharmacology
  • Rats
  • Rats, Wistar
  • Streptozocin* / pharmacology

Substances

  • Neuroprotective Agents
  • Streptozocin