Intranasal therapeutic strategies for management of Alzheimer’s disease

Abstract

Alzheimer's disease (AD) is a chronic and progressive age-related irreversible neurodegenerative disorder that represents 70% of all dementia with 35 million cases worldwide. Successful treatment strategies for AD have so far been limited, and present therapy is based on cholinergic replacement therapy and inhibiting glutamate excitotoxicity. In this context, role of neuroprotective drugs has generated considerable interest in management of AD. Recently, direct intranasal (IN) delivery of drug moieties to the central nervous system (CNS) has emerged as a therapeutically viable alternative to oral and parenteral routes. IN delivery bypasses the blood-brain barrier by delivering and targeting drugs to the CNS along the olfactory and trigeminal neural pathways which are in direct contact with both the environment and the CNS. In an attempt to understand how neurotherapeutics/nanoparticulate delivery systems can be transported from the nose to the CNS, the present review sets out to discuss the mechanism of transport from nose to brain. The aim of this review is to discuss and summarize the latest findings of some of the major studies on IN drug delivery in AD models, with a focus on the potential efficacy of neuroprotective treatments.

Intranasal Drug Delivery in Neuropsychiatry: Focus on Intranasal Ketamine for Refractory Depression

“…11 Intranasal ropinirole 18 and other intranasal treatments are being studied for Parkinson disease, and intranasal insulin and other treatments are being studied for mild cognitive impairment and early Alzheimer's disease. 13,19 A neurosteroid, PH94B, was successfully trialled for social anxiety in women. 20 INDD is also being studied for brain neoplasms.…”

Drug delivery approaches for the treatment of glioblastoma multiforme

“…As a result, intranasal drug administration leads to direct release into the CSF, which makes it an ideal approach for fast delivery of therapeutic compounds to the brain. Given the simplicity of intranasal delivery, this route of administration has received a lot of attention for its application in the treatment of GBM and other neurological disorders (Hashizume et al 2008, Sood et al 2014. It was shown in one study that administration of a therapeutic compound via intranasal delivery in rats with GBM could result in its accumulation in brain tissues as quickly as 4 h after delivery (Hashizume et al 2008).…”

Nanotechnology-based drug delivery systems for the treatment of Alzheimer’s disease

“…In the context of treating AD, these types of nanosystems could efficiently carry and deliver drugs and other neuroprotective molecules to the brain. 4,318,319 The intranasal route plays a role in overcoming the BBB and targeting the drugs directly to the brain. 282,[319][320][321][322][323][324][325] However, the oral, dermal, and intravenous routes can be used to administration of nanodevices …”

“…3 There are several limitations associated with present therapy, and the intranasal strategy seems to be a promising route for delivery of drugs to brain. 4 Currently approved drugs for treating the cognitive impairments in AD are based on neurotransmitter or enzyme modulation. 4 Acetylcholinesterase (AChE) inhibitors are associated with gastrointestinal adverse effects like nausea and vomiting that most commonly lead to discontinuation of treatment.…”

“…4 Currently approved drugs for treating the cognitive impairments in AD are based on neurotransmitter or enzyme modulation. 4 Acetylcholinesterase (AChE) inhibitors are associated with gastrointestinal adverse effects like nausea and vomiting that most commonly lead to discontinuation of treatment. 5,6 Tacrine has a short half-life and needs four administrations per day.…”