Journal
ADVANCED SCIENCE
Volume 8, Issue 14, Pages -Publisher
WILEY
DOI: 10.1002/advs.202101058
Keywords
drug delivery; hydrogel; neuroactive drugs; supramolecular gel
Categories
Funding
- Centre for Future Health (CFH1b KIT)
- Centre for Future Health (Wellcome Trust)
- Centre for Future Health (University of York)
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The study demonstrates the use of a self-assembling hydrogel as a delivery vehicle for the Parkinson's disease drug l-DOPA, showing promising results for nasal drug delivery strategies.
This paper reports the use of a self-assembling hydrogel as a delivery vehicle for the Parkinson's disease drug l-DOPA. Based on a two-component combination of an l-glutamine amide derivative and benzaldehyde, this gel has very soft rheological properties and self-healing characteristics. It is demonstrated that the gel can be formulated to encapsulate l-DOPA. These drug-loaded gels are characterized, and rapid release of the drug is obtained from the gel network. This drug-loaded hydrogel has appropriate rheological characteristics to be amenable for injection. This system is therefore tested as a vehicle for nasal delivery of neurologically-active drugs-a drug delivery strategy that can potentially avoid first pass liver metabolism and bypass the blood-brain barrier, hence enhancing brain uptake. In vitro tests indicate that the gel has biocompatibility with respect to nasal epithelial cells. Furthermore, animal studies demonstrate that the nasal delivery of a gel loaded with H-3-labeled l-DOPA out-performed a simple intranasal l-DOPA solution. This is attributed to longer residence times of the gel in the nasal cavity resulting in increased blood and brain concentrations. It is demonstrated that the likely routes of brain penetration of intranasally-delivered l-DOPA gel involve the trigeminal and olfactory nerves connecting to other brain regions.
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