Polymeric nanoparticles for CNS drug delivery: strategies and perspectives

The application of nanotechnology to health raises high expectations for a more efficient and affordable healthcare. Even if several areas of medical care could benefit from the advantages that nanotechnology can offer, a selective CNS drug delivery and targeting could improve the therapy of brain diseases which have a tremendous negative impact not only on the patient himself but also on the whole society and linked social and insurance systems. Polymeric nanoparticles (Np) have been considered as strategic carriers for the brain delivery and targeting. Specific ligands on the surface allowed the Np to cross the Blood-Brain Barrier (BBB) carrying model drugs within the brain district after their i.v. administration in experimental animals. A new strategy for Np brain targeting by using a simil-opioid peptide−derived PLGA, obtaining Np showing both the ligands for CNS targeting and the marker of fluorescence on their surface was found (M-Np). After administration, the M-Np were found to be able to cross the BBB and the ability of these M-Np to act as drug carriers has been shown (Tosi et al., 2007). Moreover, the biodistribution of M-Np showed a localization into the CNS in a quantity (15% of the injected dose) about two orders of magnitude greater than that found with the other known Np drug carriers (Vergoni et al., 2009). Moreover, it is known that sialic acid receptors are present in several organs, including in the brain parenchyma. Thus, PLGA Np modified on their surface with a BBB-crossing ligand (simil-opioid peptide) and with a sialic acid residue (SA) were prepared (SA-M-Np). This double targeting (for BBB crossing and for the interaction with brain receptors) allowed to obtain novel targeted Np with a prolonged residence within the brain parenchyma, thus letting to reach a long-lasting brain delivery of drugs. Notwithstanding an increased accumulation of SA-covered Np in those organs showing SA-receptors (liver, kidney, lung), the pharmacological and biodistribution results are proofs of the ability of double-targeted Np to enter the brain allowing the drug to be released over a prolonged time. References•Tosi G. et al., Targeting the Central Nervous System. In vivo experiments with peptide derivatized nanoparticles loaded with Loperamide and Rhodamine 123, J. Control. Release 122 (2007) 1-9.•Vergoni AV et al., Nanoparticles as drug delivery agents specific for CNS: in vivo biodistribution. Nanomedicine: Nanotechnology, Biology and Medicine 5 (2009) 369-377.