Engineered polylactide-co-glycolide(PLGA) Np as drug delivery systems for the Central Nervous System

Nanoparticulate polymeric systems (nanoparticles, Np) have been widely studied for the delivery of drugs to a specific target site. Np have been recently considered for the therapy of various brain diseases. The major problem in accessing the central nervous system (CNS) is due to the presence of the Blood-Brain Barrier (BBB). Recently, it has been shown the possibility to reach the CNS district crossing the BBB using nanoparticles (Np) made of polylactide-co-glycolide (PLGA), modified with a simil-opioid sequence and different glycosidic moieties. Firstly, PLGA was modified with different glycol-heptapetides (Glucose, Lactose, Xylose, and Mannose as sugar moieties and with a single [P] or a triple sequence of heptapeptides [3P]). Then, after i.v. administration, Np, labeled with covalent linkage with a fluorescent dye, were demonstrated to be able to cross the BBB by using confocal microscopy. A strong analgesic effects due to the encapsulated Loperamide, a P-glycoprotein (P-gp) substrate model drug, demonstrated the ability of modified PLGA Np to cross the BBB, after i.v. administration. The effect was different in the intensity and in the time period according to the different surface modification, being the Glucose preferable when compared with the other ones. When 3P-PLGA Np were used, a different profile in the pharmacological activity was assessed, i.e. a sudden maximum analgesic effect followed by a fast decrease over the time. Finally, the biodistribution of Np loaded with Rhodamine-123 (P-gp substrate) was analyzed quantifying the fluorescent intensity in the different organs including brain, in order to better understand the fate of these modified Np.