Brain Sciences (Jun 2023)

Development and In Vivo Assessment of 4-Phenyltellanyl-7-chloroquinoline-loaded Polymeric Nanocapsules in Alzheimer’s Disease Models

  • Ana Cláudia Funguetto-Ribeiro,
  • Kelly Ayumi Nakama,
  • Mikaela Peglow Pinz,
  • Renata Leivas de Oliveira,
  • Manoela do Sacramento,
  • Flávia S. Oliveira Pereira,
  • Simone Pinton,
  • Ethel Antunes Wilhelm,
  • Cristiane Luchese,
  • Diego Alves,
  • Daiana Silva Ávila,
  • Sandra Elisa Haas

DOI
https://doi.org/10.3390/brainsci13070999
Journal volume & issue
Vol. 13, no. 7
p. 999

Abstract

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Alzheimer’s disease (AD) is the most common form of dementia in older people, and available treatments are palliative and produce undesirable side effects. The 4-phenyltellanyl-7-chloroquinoline (TQ) is an organochalcogen compound studied due to its pharmacological properties, particularly its antioxidant potential. However, TQ possesses some drawbacks such as low aqueous solubility and high toxicity, thus warranting the search for tools that improve the safety and effectiveness of new compounds. Here, we developed and investigated the biological effects of TQ-loaded polymeric nanocapsules (NCTQ) in an AD model in transgenic Caenorhabditis elegans expressing human Aβ1–42 in their body–wall muscles and Swiss mice injected with Aβ25–35. The NCTQ displayed good physicochemical properties, including nanometer size and maximum encapsulation capacity. The treatment showed low toxicity, reduced Aβ peptide-induced paralysis, and activated an endoplasmic reticulum chaperone in the C. elegans model. The Aβ injection in mice caused memory impairment, which NCTQ mitigated by improving working, long-term, and aversive memory. Additionally, no changes in biochemical markers were evidenced in mice, demonstrating that there was no hepatotoxicity in the tested doses. Altogether, these findings provide insights into the neuroprotective effects of TQ and indicate that NCTQ is a promising candidate for AD treatment.

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