Can leptin-derived sequence-modified nanoparticles be suitable tools for brain delivery?

Aim: In order to increase the knowledge on the use of the nanoparticles (Np) in the brain targeting, this paper describes the conjugation of the sequence 12-32 (g21) of Leptin (Lp) to poly-lactide-co-glycolide (PLGA) Np. The capability of these modified Np to reach the brain was evaluated in rats after i.v. administration.Materials and Methods: The g21 was linked on the surface of Np labeled with tetramethylrhodamine (TRM) by means of the Avidin-Biotin technology. The g21 labeled Np were injected into the tail vein of rats and, after animal sacrifice, the brain localization was evaluated by confocal microscopy, fluorescence microscopy and electron microscopy. Studies to evaluate the biodistribution of the g21 modified Np in comparison to the un-modified Np were also carried out. Moreover, to confirm the absence of any anorectic effect of g21 linked on the surface of Np, appropriate studies were assess in the rats.Results: After i.v. administration, the g21 modified Np were able to cross the BBB and to enter the brain parenchyma. The biodistribution studies of both un-modified and modified Np pointed out an uptake at liver and spleen level, whereas only the g21 modified Np showed brain localization. The food-intake experiments pointed out that the i.v. administration of g21 conjugated to the Np surface did not produce any anorectic effect in the rats.Conclusion: g21-modified Np were able to cross the BBB. This new modified Np could be effectively considered as useful carrier systems for brain drug delivery.