Poly(ethylene glycol)-block-poly(D,L-lactide acid) micelles anchored with angiopep-2 for brain-targeting delivery

In this study, angiopep with high transcytosis capacity and parenchymal accumulation was used as a novel ligand for the brain-targeting delivery of poly(ethylene glycol)-block-poly(D,L-lactide acid) (PEG-PLA) micelles. Angiopep-2 was synthesized by solid-phase peptide synthesis, and then conjugated with maleimide-PEG-PLA to form angiopep-PEG-PLA. The micelles composed of methoxy-PEG-PLA (mPEG-PLA) and angiopep-PEG-PLA was prepared by film-hydration method. Near-infrared fluorescence dye, DiR was loaded into micelles to evaluate the brain-targeting ability of micelles with or without angiopep modification by near-infrared fluorescence imaging in vivo and ex vivo. Significant near-infrared (NIR) fluorescent signal was detected in the brain after angiopep-anchored micelles administration and further confirmed by imaging the whole brain and brain slices, compared with that of the micelles without modification. I-125-radiolabeled angiopep-PEG-PLA micelles after intravenous administration in mice showed high brain accumulation for up to 24 h. These results indicate that angiopep-modified PEG-PLA micelle is a promising brain-targeting nanocarrier for lipophilic drugs.