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Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Pharmacology

Background:

  • Hepatic stellate cells (HSCs) are key drivers of liver fibrosis.
  • Developing targeted therapies is crucial for effective fibrosis management.

Purpose of the Study:

  • To develop and evaluate vitamin A-functionalized nanoparticles for targeted delivery of bortezomib (BTZ) to activated HSCs.
  • To assess the efficacy of this targeted delivery system in a mouse model of liver fibrosis.

Main Methods:

  • Nanoparticles (NPs) were synthesized using emulsion solvent evaporation and functionalized with vitamin A.
  • NP characterization involved FT-IR, DLS, and SEM; biodistribution and in vitro cytotoxicity were assessed.
  • Efficacy was evaluated in a mouse liver fibrosis model through serological, molecular, and histopathological analyses.

Main Results:

  • Characterization confirmed optimal NP size and successful drug entrapment.
  • Biodistribution studies showed preferential accumulation of NPs in the liver.
  • Treatment with BTZ-loaded targeted NPs significantly reduced collagen I, collagen III, and α-SMA expression, and suppressed TGF-β1/Smad3 and NF-κB pathways.

Conclusions:

  • Low-dose BTZ encapsulated in targeted nanoparticles can effectively ameliorate liver fibrosis.
  • This targeted delivery approach shows significant therapeutic potential for liver fibrosis.