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<p>The massive impact of neurological disease globally has posed a question for its control and management. The blood–brain barrier is a great hindrance to the delivery of drugs across the brain, restricting the passage of drug molecules and limiting their effectiveness. Our study aims to investigate the potential of increasing permeability to the BBB by formulating cationic solid lipid nanoparticles (cSLNs) loaded with quercetin and evaluated against the adult zebrafish model, with an attempt to improve the stability profiles of SLNs by using an optimized blend of lipids. The cSLNs show the size range and zeta-potential (131.6 ± 3.9 and 26.5 ± 1.67), respectively. The neuroprotective activity of the optimized QCT-loaded cSLNs was also investigated using the hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>)-induced zebrafish model. Various behavioral and biochemical parameters were analyzed, and the study revealed that the higher efficacy of the cSLNs, which is attributed to their inherent cationic charge, may facilitate binding to the negatively charged endothelial cells of the blood–brain barrier (BBB). The formulation adheres to the BBB, and drug molecules get released, easily crossing the BBB, thereby showing its improved action. Further, the blend of lipids used slowed the degradation of nanoparticles and improved their stability aspects.</p>

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QbD-Optimized Quercetin-Loaded Cationic SLNs Enhance Neuroprotection in H₂O₂-Induced Alzheimer’s Zebrafish Model

  • 期刊论文

  • 发表日期：

    2025年10月21日

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  • Gurisha Garg,
  • Arti Singh,
  • Preeti Patel,
  • Manish Kumar,
  • Shubham Thakur,
  • Balak Das Kurmi

摘要

The massive impact of neurological disease globally has posed a question for its control and management. The blood–brain barrier is a great hindrance to the delivery of drugs across the brain, restricting the passage of drug molecules and limiting their effectiveness. Our study aims to investigate the potential of increasing permeability to the BBB by formulating cationic solid lipid nanoparticles (cSLNs) loaded with quercetin and evaluated against the adult zebrafish model, with an attempt to improve the stability profiles of SLNs by using an optimized blend of lipids. The cSLNs show the size range and zeta-potential (131.6 ± 3.9 and 26.5 ± 1.67), respectively. The neuroprotective activity of the optimized QCT-loaded cSLNs was also investigated using the hydrogen peroxide (H2O2)-induced zebrafish model. Various behavioral and biochemical parameters were analyzed, and the study revealed that the higher efficacy of the cSLNs, which is attributed to their inherent cationic charge, may facilitate binding to the negatively charged endothelial cells of the blood–brain barrier (BBB). The formulation adheres to the BBB, and drug molecules get released, easily crossing the BBB, thereby showing its improved action. Further, the blend of lipids used slowed the degradation of nanoparticles and improved their stability aspects.