Cancers 2013, 5(3), 1020-1048; doi:10.3390/cancers5031020
Formulations for Intranasal Delivery of Pharmacological Agents to Combat Brain Disease: A New Opportunity to Tackle GBM?
1
Laboratory of Experimental Neurosurgery and Neuroanatomy, KU Leuven, Leuven 3000, Belgium
2
Laboratory of Pediatric Immunology, KU Leuven, Leuven 3000, Belgium
3
Laboratory of Pharmaceutics and Biopharmaceutics, ULB, Brussels 1050, Belgium
4
Laboratory of Toxicology, ULB, Brussels 1050, Belgium
5
Department of Neurosurgery, Erasmus University Hospitals, Brussels 1050, Belgium
6
Department of Neurosurgery, University Hospitals Leuven, Leuven 3000, Belgium
*
Author to whom correspondence should be addressed.
Received: 29 June 2013 / Revised: 29 June 2013 / Accepted: 2 August 2013 / Published: 14 August 2013
(This article belongs to the Special Issue Glioblastoma)
Abstract
Despite recent advances in tumor imaging and chemoradiotherapy, the median overall survival of patients diagnosed with glioblastoma multiforme does not exceed 15 months. Infiltration of glioma cells into the brain parenchyma, and the blood-brain barrier are important hurdles to further increase the efficacy of classic therapeutic tools. Local administration methods of therapeutic agents, such as convection enhanced delivery and intracerebral injections, are often associated with adverse events. The intranasal pathway has been proposed as a non-invasive alternative route to deliver therapeutics to the brain. This route will bypass the blood-brain barrier and limit systemic side effects. Upon presentation at the nasal cavity, pharmacological agents reach the brain via the olfactory and trigeminal nerves. Recently, formulations have been developed to further enhance this nose-to-brain transport, mainly with the use of nanoparticles. In this review, the focus will be on formulations of pharmacological agents, which increase the nasal permeation of hydrophilic agents to the brain, improve delivery at a constant and slow release rate, protect therapeutics from degradation along the pathway, increase mucoadhesion, and facilitate overall nasal transport. A mounting body of evidence is accumulating that the underexplored intranasal delivery route might represent a major breakthrough to combat glioblastoma.Keywords:
glioblastoma multiforme; intranasal administration; nose-to-brain delivery; formulations; nanoparticles; drug delivery; new therapy concept
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).
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MDPI and ACS Style
van Woensel, M.; Wauthoz, N.; Rosière, R.; Amighi, K.; Mathieu, V.; Lefranc, F.; van Gool, S.W.; de Vleeschouwer, S. Formulations for Intranasal Delivery of Pharmacological Agents to Combat Brain Disease: A New Opportunity to Tackle GBM? Cancers 2013, 5, 1020-1048.