Targeted brain delivery of itraconazole via RVG29 anchored nanoparticles.

The blood-brain barrier is a major barrier in the neurological diseases treatment and precludes the entry of drugs from blood to brain. Here, we developed 29-amino-acid peptide derived from rabies virus glycoprotein (RVG29) peptide conjugated itraconazole-loaded albumin nanoparticles (RVG29-ITZ-NPs). The RVG29 peptide was conjugated to the albumin NPs using biotin-binding streptavidin as crosslinker. The NPs were characterized in terms of particle size, zeta potential, drug loading and release behavior in vitro. Cellular uptake of RVG29-ITZ-NPs was investigated by flow cytometry. Pharmacokinetics and brain distribution of RVG29-ITZ-NPs were investigated after intravenous administration of NPs. The particle size of RVG29-ITZ-NPs was 89.3 ± 1.9 nm as determined by dynamic light scattering. The zeta potential of RVG29-ITZ-NPs was -33.1 ± 0.9 mV. RVG29-ITZ-NPs exhibited a sustained release profile within 24 h. In vitro cellular uptake studies demonstrated that RVG29 significantly facilitated the intracellular delivery of NPs. A significant (P < 0.05) accumulation of ITZ in brain was observed for RVG29-ITZ-NPs as compared with ITZ-NPs and cyclodextrin formulation of ITZ (ITZ-CD). These results suggested that RVG29-ITZ-NPs can be exploited as a potential therapeutic formulation for the intracranial fungal infection.