Nose-to-brain drug delivery for the treatment of Alzheimer’s disease: current advancements and challenges

ABSTRACT

Introduction

The irreversible destruction of neurons, progressive loss of memory and cognitive behavior, high cost of therapy, and impact on society, desire a better, effective, and affordable treatment of AD. The nose-to-brain delivery approach holds great potential to access the brain without any hindrance of BBB and results in higher bioavailability and thus better therapeutic efficacy of anti-AD drugs.

Areas covered

The present review article highlights the current facts and worldwide statistics of AD and its detailed etiology. This is followed by barriers to brain delivery, nose-to-brain delivery, their limitations, and amalgamation with various novel carrier systems. We have emphasized recent advancements in nose-to-brain delivery using mucoadhesive, stimuli-responsive carriers, polymeric nanoparticles, lipid nanoparticles, and protein/peptide delivery for treatment of AD.

Expert opinion

The available therapies are symptomatic and mitigate the symptoms of AD at the initial stages. In lieu of this, nose-to-brain delivery has the ability to overcome these limitations and increase drug bioavailability in the brain. Various novel strategies including stimuli-responsive systems, nanoparticles, etc. enhance the nasal permeation, protect the drug, and enhance its therapeutic potency. However, successful preclinical data do not assure the clinical success of the therapy, and hence exhaustive clinical investigations are needed to make the therapy available for patients.

Graphical Abstract

KEYWORDS:

• Alzheimer’s Disease
• Brain Targeting
• Cellular Transport
• Amyloid aggregation
• Tau hyperphosphorylations
• Nose-to-Brain delivery

Article highlights

• Nose-to-brain delivery offers a potential and alternative route of drug delivery to the brain through the olfactory and trigeminal nerve pathways.

• Bypassing the BBB, first-pass metabolism, GIT, and systemic exposure significantly increases the brain bioavailability and reduces systemic toxicity.

• The use of novel strategies like mucoadhesive system, stimuli-responsive system, and nanocarriers overcomes the limitations of the nose-to-brain delivery route.

• Stimuli-triggered novel drug carrier enhances nasal retention time, thus facilitating the drug permeation and easing the nasal administration.

• Nanoparticles are suitable for the delivery of hydrophilic, lipophilic, and large protein-/peptide-based bioactives. These novel carriers protect the drug from enzymatic degradation, enhance nasal permeation, target the drug to the specific site of action, and increase therapeutic efficacy in preclinical studies

• On the contrary, the outcome of preclinical investigations fails to replicate at the clinical level due to a variety of physiological factors. A better understanding of etiological factors and exhaustive clinical investigations are needed to develop a promising therapy.

This box summarizes key points contained in the article.

Acknowledgments

The author would like to acknowledge the support provided by the National Institute of Pharmaceutical Education and Research (NIPER), Guwahati.

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 in this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.