Peptide-derivatized biodegradable nanoparticles able to cross the blood–brain barrier

Injectable nanoparticulate drug carriers (Np) able to cross the blood–brain barrier (BBB) have important potential applications for the treatment of diseases that affect the central nervous system (CNS). With the aim to create a system able to address Np to the CNS, we synthesized conjugates between a biodegradable copolymer, poly( d, l-lactide-co-glycolide) (PLGA), and five short peptides, by means of an amidic linkage. These peptides, that are similar to synthetic opioid peptides, were synthesized in turn by means of Fmoc solid-phase peptide synthesis. The new five modified copolymers thus obtained turned out to be valuable starting material for the preparation of Np; these were made fluorescent, in order to allow their localization after their administration, by inclusion of a fluorescent probe. The Np thus prepared were characterized (morphology, size and z-potential) and were shown to possess the peptidic moieties on their surface, as evidenced by ESCA spectroscopy. Then, their ability to cross the BBB was assessed by the in vivo Rat Brain Perfusion Technique and, in one case, by means of a systemic administration (rat femoral vein injection). Fluorescent and confocal microscopy studies showed that while PLGA Np are unable to cross the BBB, for the first time these solid Np surface-modified with peptides were shown to be able to cross the BBB.