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This study developed nanostructured lipid carriers (NLCs) for intranasal delivery of Butyrylcholinesterase (RV) and Kinase Inhibitors (KI) to treat Alzheimer's disease (AD). The RV-KI-NLC formulation effectively reversed AD-like symptoms and protected neurons.

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Biotechnology

Background:

  • Alzheimer's disease (AD) is a progressive neurodegenerative disorder with limited treatment options.
  • Intranasal delivery of nanostructured lipid carriers (NLCs) can enhance drug bioavailability to the brain.
  • This study focuses on NLCs loaded with Butyrylcholinesterase (RV) and Kinase Inhibitors (KI) for targeted AD therapy.

Purpose of the Study:

  • To investigate the efficacy of intranasal RV-KI-NLCs for Alzheimer's disease (AD) treatment.
  • To evaluate the neuroprotective and cognitive-enhancing effects of the RV-KI-NLC formulation.
  • To assess the pharmacokinetic, biodistribution, and pharmacodynamic properties of RV-KI-NLCs.

Main Methods:

  • Developed and characterized NLCs using a modified emulsification method.
  • Utilized a scopolamine-induced AD-like symptoms model in Wistar rats.
  • Conducted pharmacokinetic, biodistribution, pharmacodynamic (NOR, EPM), immunohistochemistry, histopathology, and antioxidant (DPPH) assays.

Main Results:

  • RV-KI-NLCs demonstrated significant neuroprotection, mitigating scopolamine-induced neuronal damage and inflammation.
  • Treatment with RV-KI-NLCs reduced key AD biomarkers (BACE1, TNF-α) and improved neuronal integrity.
  • Significant improvements in cognitive and behavioral functions were observed in NOR and EPM tests, correlating with antioxidant activity.

Conclusions:

  • The RV-KI-NLC formulation exhibits superior neuroprotective effects and cognitive enhancement in an AD model.
  • Intranasal delivery of RV-KI-NLCs represents a promising therapeutic strategy for Alzheimer's disease.
  • The formulation's strong antioxidant activity contributes to its overall efficacy in mitigating AD pathology.