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Drug Development.

Sambita Panda1, Sachin Kumar Singh2, Bushra Bashir2

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Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 25, 2025
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Summary
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A novel self-emulsifying drug delivery system (SNEDDS) enhanced the delivery of Isorhamnetin (IH) for Alzheimer's disease (AD) treatment. This improved cognitive function and reduced key AD biomarkers in rat models.

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Biochemistry

Background:

  • Alzheimer's disease (AD) is a neurodegenerative disorder characterized by amyloid plaques, tau tangles, neuroinflammation, and oxidative stress.
  • Isorhamnetin (IH) exhibits neuroprotective properties against AD by inhibiting key inflammatory pathways.
  • Poor solubility, bioavailability, and blood-brain barrier (BBB) penetration limit IH's therapeutic efficacy.

Purpose of the Study:

  • To develop an Isorhamnetin (IH)-loaded self-emulsifying drug delivery system (SNEDDS) to overcome delivery challenges.
  • To evaluate the neuroprotective effects and therapeutic potential of IH-loaded SNEDDS in an Alzheimer's disease model.

Main Methods:

  • An optimized IH-loaded SNEDDS formulation was developed and characterized for particle size, PDI, zeta potential, and drug loading.
  • Pharmacodynamic studies using the Morris Water Maze test assessed cognitive and motor functions in rats.
  • Biochemical analyses measured Alzheimer's disease markers, including acetylcholinesterase (AChE) levels, amyloid-beta, oxidative stress, and neuroinflammation.

Main Results:

  • The optimized IH-SNEDDS formulation exhibited favorable characteristics, including a droplet size of 59.46 nm, PDI of 0.3, zeta potential of -19 mV, and 96% drug loading.
  • Significant improvements in cognitive and motor functions were observed in rats treated with IH-SNEDDS at high doses.
  • The formulation effectively reduced AChE levels, amyloid-beta deposition, oxidative stress, and neuroinflammation, indicating a therapeutic effect.

Conclusions:

  • IH-loaded SNEDDS represents a promising therapeutic strategy for managing Alzheimer's disease.
  • The developed SNEDDS formulation enhances the delivery and efficacy of Isorhamnetin for treating AD.
  • This approach addresses the limitations of IH, offering improved bioavailability and BBB penetration for neuroprotection.