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Solid Lipid Nanoparticles (SLNs) for Intracellular Targeting Applications
Published on: November 17, 2015
Brain targeting using novel lipid nanovectors
Arnaud Béduneau1, François Hindré, Anne Clavreul
1Inserm, U646, Angers, F-49100 France, Université d'Angers, Angers, F-49100 France.
Abstract:
The present study shows the potential of novel nanovectors for the delivery of lipophilic radionuclides and therapeutic molecules to the brain. Lipid nanocapsules (LNC) inhibiting the P-gp pump efflux, were conjugated to OX26 monoclonal antibodies (OX26 MAb) and Fab' fragments. The OX26 MAb is directed against the transferrin receptor (TfR) highly expressed on the cerebral endothelium. The specific association of immunonanocapsules to rat brain capillary endothelial cells was demonstrated. Biodistribution of immunonanocapsules, labeled with a (188)Re lipophilic complex, was determined in healthy rats. At 24 h post-injection, the brain concentrations of Fab'-immunonanocapsules and OX26-immunonanocapsules were, respectively, 1.5 and 2-fold higher than non-targeted nanocapsules. In addition, Fab' fragments helped prolong the vascular residence time of the nanovectors but their affinity to TfR was lower than whole antibodies. The ability of immunonanocapsules to specifically target cerebral tissues in addition to the promising features of LNC is of importance to the field of nanomedicine.
Insights
Novel nanovectors, lipid nanocapsules (LNC) conjugated with antibodies, show promise for delivering drugs to the brain. These targeted nanovectors significantly increased brain concentrations compared to non-targeted ones.
Area of Science:
- Nanomedicine
- Neuroscience
- Biotechnology
Background:
- Developing effective brain drug delivery systems is challenging due to the blood-brain barrier.
- Lipid nanocapsules (LNC) are promising nanocarriers for drug delivery.
- Targeting specific receptors on the cerebral endothelium can enhance brain penetration.
Purpose of the Study:
- To evaluate novel antibody-conjugated lipid nanocapsules (LNC) for targeted delivery of lipophilic radionuclides and therapeutics to the brain.
- To assess the efficacy of OX26 monoclonal antibody (OX26 MAb) and Fab' fragments in targeting the transferrin receptor (TfR) on brain endothelial cells.
- To determine the biodistribution and brain accumulation of targeted LNC in vivo.
Main Methods:
- Conjugation of LNC with OX26 MAb and Fab' fragments targeting the transferrin receptor (TfR).
- In vitro demonstration of specific association of immunonanocapsules with rat brain capillary endothelial cells.
- In vivo biodistribution studies in healthy rats using (188)Re-labeled lipophilic immunonanocapsules.
Main Results:
- Immunonanocapsules showed specific binding to brain capillary endothelial cells.
- Brain concentrations of Fab'-immunonanocapsules and OX26-immunonanocapsules were 1.5- and 2-fold higher, respectively, than non-targeted LNC at 24 hours.
- Fab' fragments prolonged nanovector vascular residence time, but whole antibodies exhibited higher TfR affinity.
Conclusions:
- Antibody-conjugated LNC effectively target the brain's transferrin receptor, enhancing brain accumulation of nanovectors.
- This targeted nanodelivery approach holds significant potential for treating brain diseases.
- Further research into optimizing nanovector design, like fragment selection, is warranted for improved therapeutic outcomes.
