Enhanced Delivery of Neuroactive Drugs via Nasal Delivery with a Self-Healing Supramolecular Gel
![a,b) Rheological study of gel formed by compound 1 (0.46% w/v) in water showing a) response of storage and loss modulus (G′, blue and G″, orange) to strain and b) the shear viscosity over time. At 200 s, a large strain is applied to the sample, which was then left to recover its gel-like characteristics—this process took 40 s. c) (Left) SEM image of hydrogel formed from 1 loaded 1:1 with l-DOPA, (right) TEM image of hydrogel formed from 1 loaded 1:1 with l-DOPA. d) Release of l-DOPA in vitro from the hydrogel formed by 1 loaded with l-DOPA (0.8 x 10–3m).](https://www.pharmaexcipients.com/wp-content/uploads/2021/07/Enhanced-Delivery-of-Neuroactive-Drugs-via-Nasal-Delivery-with-a-Self-Healing-Supramolecular-Gel.jpg)
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 3H-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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Article information: Enhanced Delivery of Neuroactive Drugs via Nasal Delivery with a Self-Healing Supramolecular Gel. Adv. Sci. 2021, 8, 2101058. https://doi.org/10.1002/advs.202101058
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