Intranasal Drug Delivery for Brain Targeting

Abstract

Many drugs are not being effectively and efficiently delivered using conventional drug delivery approach to brain or central nervous system (CNS) due to its complexity. The brain and the central nervous system both have limited accessibility to blood compartment due to a number of barriers. Many advanced and effective approaches to brain delivery of drugs have emerged in recent years. Intranasal drug delivery is one of the focused delivery options for brain targeting, as the brain and nose compartments are connected to each other via the olfactory route and via peripheral circulation. Realization of nose to brain transport and the therapeutic viability of this route can be traced from the ancient times and has been investigated for rapid and effective transport in the last two decades. Various models have been designed and studied by scientists to establish the qualitative and quantitative transport through nasal mucosa to brain. The development of nasal drug products for brain targeting is still faced with enormous challenges. A better understanding in terms of properties of the drug candidate, nose to brain transport mechanism, and transport to and within the brain is of utmost importance. This review will discuss some pertinent issues to be considered and challenges to brain targeted intranasal drug delivery. A few marketed and investigational drug formulations will also be discussed.

Development and evaluation of thymoquinone-encapsulated chitosan nanoparticles for nose-to-brain targeting: a pharmacoscintigraphic study

“…Recent evidence of direct nose-to-brain transport and direct access to CSF of neuropeptides bypassing the bloodstream has been shown in human trials, despite the inherent difficulties of delivery. 16,17 Intranasal delivery is noninvasive and essentially painless, does not require sterility regulations, and is readily administered by the patient or health professionals. DDS are designed to promote the localized therapeutic effect and minimize toxic side effects.…”

“…The mucoadhesive polymeric NPs of TQ that we developed are expected to offer many advantages over conventional nasal dosage forms, such as increased nasal residence and possibility of drug release at a slow and constant rate to the brain. 17,19,20 As part of the development studies for TQ delivery into the brain, the objective of the present study was to simultaneously investigate the plasma pharmacokinetics and brain distribution profiles of the TQ-loaded NPs in Wistar rats after intravenous and intranasal administration and to assess whether there is a direct nose-to-brain transport pathway.…”

Development of a new HPLC method for in vitro and in vivo studies of haloperidol in solid lipid nanoparticles

“…PValue < 0.05 was considered statistically significant. The extent of nose-to-brain delivery could be evaluated by many parameters (Abdelbeary, Tadros, 2013): (i) The brain/blood ratio, at 0.5 h, following intranasal and intravenous administration (Vyas et al, 2005). (ii) The relative bioavailability (RB) percentages following the intranasal administration in the blood and brain (MD et al, 2012).…”

Nanotechnology platforms in Parkinson’s Disease

“…However, mucocilliary clearance limits the residence time when drug solutions are delivered intranasally. [90]. Recently, Wen et al (2011) demonstrated that intranasal administration showed improved therapeutic efficacy of urocortin (corticotrophin releasing factor related peptide) when encapsulated in Odorranalectin (bioadhesive from lectin family) functionalized PEG-PLGA nanoparticles in hemiparkinsonian rats [91].…”