Access to the central nervous system (CNS) is regulated by the blood brain barrier (BBB). The BBB providesstringent control on the extracellular neuronal environment thereby supporting proper function;unfortunately, it acts at the same time as a substantial limit to drug delivery to the CNS.Chitosan nanoparticles (ChiNPs) are biocompatible drug carriers able to pass biological barriers and the cellmembrane: in particular, ChiNPs can cross the blood brain barrier, thus representing a promising deliverysystem to CNS. In this work we tested the ability of ChiNPs to deliver the syntethic opiod DADLE (D-Ala2-DLeu5-enkephalin) to cultured B50 rat neuronal cells. DADLE is able to induce reversible hypometabolizingeffects, representing a promising agent for neuroprotection, preservation of explanted organs and antitumourtreatments. Since DADLE has a short plasmatic half-life and is unable to cross the blood brainbarrier, its encapsulation in ChiNPs would allow the blood brain barrier to be crossed and the peptide beprotected from enzymatic degradation.We demonstrate by immunoelectron microscopy that ChiNPs are efficient opioid carriers to neuronal cells,protecting incorporated molecules from enzymatic degradation and prolonging their intracellular effects.DADLE is released from ChiNPs inside the call for up to 48h. It binds to the nuclear transcription/splicingsites, decreasing transcriptional activity without damaging cell organelles.In conclusion, these results pave the way to in vivo experiments aimed at elucidating whether DADLEloadedchitosan NPs may efficiently deliver the opioid to the central nervous system.
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