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Abhinav Agarwal1, Himanshu Agrawal, Shailja Tiwari

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Engineered solid lipid nanoparticles (SLNs) conjugated with cationic bovine serum albumin (CBSA) show enhanced delivery of doxorubicin (DOX) across the blood-brain barrier. This targeted delivery improves anti-cancer efficacy and reduces immunogenicity.

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Area of Science:

  • Nanotechnology
  • Pharmacology
  • Biomedical Engineering

Background:

  • The blood-brain barrier (BBB) poses a significant challenge for delivering therapeutic agents, particularly anti-cancer drugs, to the brain.
  • Engineered nanoparticles offer potential strategies to overcome the BBB and improve drug targeting.
  • Solid lipid nanoparticles (SLNs) are a promising drug delivery system due to their biocompatibility and potential for modification.

Purpose of the Study:

  • To evaluate the efficacy of engineered solid lipid nanoparticles (SLNs) as vectors for bypassing the blood-brain barrier.
  • To investigate the potential of doxorubicin (DOX)-loaded SLNs conjugated with cationic bovine serum albumin (CBSA) for enhanced brain delivery and anti-cancer activity.
  • To assess the safety and immunogenicity of the developed nanoparticle formulation.

Main Methods:

  • Preparation and characterization of doxorubicin (DOX)-loaded solid lipid nanoparticles (SLNs) conjugated with cationic bovine serum albumin (CBSA) using FTIR, NMR, and TEM.
  • Determination of physicochemical parameters including particle size, polydispersity index, and zeta-potential.
  • In vitro cellular uptake studies on HNGC-1 cell lines, transendothelial studies across brain capillary endothelial cells, and in vivo pharmacokinetic and biodistribution studies.

Main Results:

  • CBSA-conjugated SLNs demonstrated a significant, approximately six-fold increase in cellular uptake compared to plain DOX solution.
  • The CBSA-conjugated formulation exhibited enhanced cytotoxicity against cancer cells compared to free DOX or unconjugated SLNs.
  • Transendothelial studies confirmed superior transcytosis of CBSA-conjugated SLNs across brain capillary endothelial cells, with in vivo studies showing efficient spatial and temporal DOX delivery to brain tissues.
  • Hematological, nephrotoxic, and hepatotoxic assessments indicated that CBSA-conjugated formulations were less immunogenic than plain formulations.

Conclusions:

  • Engineered solid lipid nanoparticles (SLNs) conjugated with CBSA are effective vectors for overcoming the blood-brain barrier.
  • This targeted delivery system enhances the efficacy of doxorubicin (DOX) for brain cancer treatment.
  • The CBSA-conjugated SLNs present a safer, less immunogenic alternative for drug delivery to the brain.