Nanoparticles as carriers for drug delivery of macromolecules across the blood-brain barrier

ABSTRACT

Introduction: Current therapies of neurodegenerative or neurometabolic diseases are, to a large extent, hampered by the inability of drugs to cross the blood-brain barrier (BBB). This very tight barrier severely restricts the entrance of molecules from the blood into the brain, especially macromolecular substances (i.e. neurotrophic factors, enzymes, proteins, as well as genetic materials). Due to their size, physicochemical properties, and instability, the delivery of these materials is particularly difficult.

Areas covered: Recent research showed that biocompatible and biodegradable nanoparticles possessing tailored surface properties can enable a delivery of drugs and specifically of macromolecules across the blood-brain barrier by using carrier systems of the brain capillary endothelium (Trojan Horse strategy). In the present review, the state-of-art of nanoparticle-mediated drug delivery of different macromolecular substances into the brain following intravenous injection is summarized, and different nanomedicines that are used to enable the transport of neurotrophic factors and enzymes across the blood-brain barrier into the CNS are critically analyzed.

Expert opinion: Brain delivery of macromolecules by an intravenous application using nanomedicines is now a growing area of interest which could be really translated into clinical application if dedicated effort will be given to industrial scale-up production.

KEYWORDS:

• BDNF
• blood-brain barrier (BBB)
• enzymes
• enzyme replacement therapy (ERT)
• GDNF
• lysosomal storage diseases (LSDs)
• macromolecules
• nanomedicine
• nanoparticles
• neurotrophic factor
• nerve growth factor (NGF)

Article highlight

• Brain delivery of proteins and enzymes is an important and open issue in the field of treatment of central nervous system (CNS) diseases.

• The blood-brain barrier (BBB) represents one of the major obstacles for drugs and especially macromolecules to be efficacious at the CNS level.

• Nanomedicine and in particular polymeric nanoparticles if properly engineered could overcome this limitation, with relevant preclinical evidences of brain delivery of both, neurotrophic factors and enzymes targeted to the CNS.

• Future evolution of nanomedicine for CNS delivery of macromolecules is linked to efforts for industrial scale-up to finally enable the improvement of CNS disease treatments.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The author gratefully thanks MAECI for support (grant n. MAE0066134, PI G. Tosi).