Lipid nanoparticles for intranasal administration: application to nose-to-brain delivery

ABSTRACT

Introduction: The blood brain barrier is a functional barrier allowing the entry into the brain of only essential nutrients, excluding other molecules. Its structure, although essential to keep the harmful entities out, is also a major roadblock for pharmacological treatment of brain diseases. Several alternative invasive drug delivery approaches, such as transcranial drug delivery and disruption of blood brain barrier have been explored, with limited success and several challenges. Intranasal delivery is a non-invasive methodology, which bypasses the systemic circulation, and, through the intra- and extra- neuronal pathways, provides direct brain drug delivery. Colloidal drug delivery systems, particularly lipidic nanoparticles offer several unique advantages for this goal .

Areas covered: This review focuses on key brain diseases such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease and amyotrophic lateral sclerosis, and provide a detailed overview of the current lipid nanoparticle based treatment options explored thus far. The review also delves into basic preparation, challenges and evaluation methods of lipid drug delivery systems.

Expert opinion: Brain diseases present complex pathophysiology, in addition to the practically inaccessible brain tissues, hence according to the authors, a two-pronged approach utilizing new target discovery coupled with new drug delivery systems such as lipid carriers must be adopted.

KEYWORDS:

• Neurodegenerative diseases
• intranasal delivery
• lipid nanoparticles
• drug delivery

Article highlights

• 98% of current marketed pharmaceuticals are ineffective in treating cerebral diseases, mainly because of the presence of blood brain barrier

• Intranasal delivery is the simpler and direct way for brain targeting, which avoids bloodstream clearance and invasive methods is nose-to-brain delivery

• Nanoparticles can improve nose-to-brain drug delivery, by enhanced bioadhesion to nasal mucosa, and by protecting the encapsulated drug from biological degradation, and from extracellular transport by P-gp efflux proteins

• Owing to their biocompatibility, stability, ease of surface functionalization and scale-up, lipid nanoparticles have been recently employed for intranasal delivery for different applications

• All neurodegenerative disorders, that are treated through chronic drug therapy, are suitable for nose-to-brain approach

• Neurological disorders should benefit of a two-pronged approach, utilizing new target discovery coupled with new drug delivery systems such as lipidic carriers

This box summarizes key points contained in the article.

Declaration of interest

S Swaminathan: the ideas presented in this work are his own personal views and are not endorsed by his employer. The review should not be construed as the position of the employer of S Swaminathan. S Swaminathan did not receive any funding support from his employer for writing this review 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. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The authors thank the Italian Ministry of Education University and Research (MIUR) for funding (Ricerca Locale 2015).