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Methotrexate-Loaded Solid Lipid Nanoparticles: Protein Functionalization to Improve Brain Biodistribution.

Elisabetta Muntoni1, Katia Martina2, Elisabetta Marini3

  • 1Dipartimento di Scienza e Tecnologia del Farmaco, Università degli Studi di Torino, 10124 Torino, Italy. elisabetta.muntoni@unito.it.

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Functionalized nanoparticles effectively crossed the blood-brain barrier, enhancing glioblastoma chemotherapy delivery. Transferrin or insulin-coated nanoparticles showed improved targeting of brain tumor cells.

Keywords:
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Area of Science:

  • Nanotechnology
  • Neuro-oncology
  • Pharmacology

Background:

  • Glioblastoma is an aggressive brain tumor with poor prognosis.
  • Effective chemotherapy delivery across the blood-brain barrier (BBB) is crucial for treatment.
  • Nanoparticles offer a promising strategy to overcome BBB limitations.

Purpose of the Study:

  • To develop and evaluate functionalized solid lipid nanoparticles (SLNs) for glioblastoma chemotherapy delivery.
  • To investigate the ability of transferrin or insulin-functionalized SLNs to cross the BBB.
  • To assess the biodistribution and drug metabolite profiles of methotrexate-loaded SLNs in vivo.

Main Methods:

  • SLNs were prepared using fatty acid coacervation and loaded with a methotrexate ester.
  • Nanoparticles were functionalized with transferrin or insulin via maleimide chemistry.
  • In vitro BBB models and in vivo biodistribution studies in Wistar rats were conducted.

Main Results:

  • Functionalization with transferrin or insulin enhanced nanoparticle BBB penetration.
  • The use of a PEG spacer further improved BBB crossing and target selectivity.
  • Drug metabolites, including 7-hydroxymethotrexate, were detected in the animal model.

Conclusions:

  • Functionalized SLNs show potential for targeted glioblastoma chemotherapy delivery.
  • Surface modification strategies, particularly with PEG spacers, are key for BBB traversal.
  • This approach may improve therapeutic outcomes for patients with glioblastoma.