title: Intranasal delivery of therapeutic proteins for neurological diseases.
abstract: BACKGROUND
  Among the range of therapeutic protein candidates for new generation treatments of neurological diseases, neurotrophic factors and recombinant antibodies hold the greatest potential. However, major difficulties in their safe and effective delivery to the brain severely limit these applications. The BBB restricts the exchange of proteins between the plasma and the CNS. Moreover, therapeutic proteins often need to be selectively targeted to the brain, while minimizing their biodistribution to systemic compartments, to avoid peripheral side effects. The intranasal delivery of proteins has recently emerged as a non-invasive, safe and effective method to target proteins to the CNS, bypassing the BBB and minimizing systemic exposure.
  
  
  METHODS
  We critically summarize the main experimental and mechanistic facts about the simple and non-invasive nasal delivery approach, which provides a promising strategy and a potential solution for the severe unmet medical need of safely and effectively delivering protein therapeutics to the brain.
  
  
  CONCLUSIONS
  The intranasal route for the effective delivery of recombinant therapeutic proteins represents an emerging and promising non-invasive strategy. Future studies will achieve a detailed understanding of pharmacokinetic and mechanisms of delivery to optimize formulations and fully exploit the nose-to-brain interface in order to deliver proteins for the treatment of neurological diseases. This expanding research area will most likely produce exciting results in the near future towards new therapeutical approaches for the CNS.
authors: Scuola Normale Superiore, Piazza dei Cavalieri 7, 56126 Pisa, Italy.
authors: Francesca
authors: F
authors: Malerba
authors: Francesca
authors: F
authors: Paoletti
authors: Simona
authors: S
authors: Capsoni
authors: Antonino
authors: A
authors: Cattaneo