Summary: Researchers have developed a nasal gel formulation containing levodopa that adheres to nasal tissue and releases the drug into the bloodstream and brain. Early animal studies indicate effective delivery and improved brain uptake.
Source: University of York
Scientists at the University of York report progress toward a nasal spray treatment designed to improve delivery of Parkinson’s disease medication to the brain.
The team has created a soft, self-assembling gel that carries levodopa and can be administered intranasally. The formulation is liquid for easy application and quickly forms a thin gel layer on nasal mucosa, increasing residence time and promoting direct transport of the drug toward the brain.
Levodopa (l‑DOPA) is converted into dopamine in the brain and remains the primary treatment for Parkinson’s disease symptoms caused by loss of dopamine-producing neurons. Over time, oral levodopa can become less effective because of metabolic breakdown and limited transport to the brain, requiring higher doses or alternative delivery routes. Nasal delivery offers a promising pathway to bypass some systemic metabolism and exploit direct nose-to-brain routes via the olfactory and trigeminal nerves.
Professor David Smith of the University of York’s Department of Chemistry explained that current oral therapies are effective initially but are increasingly degraded before reaching the brain, which can necessitate larger doses or injections in advanced stages. He and colleagues focused on overcoming the challenge of getting a formulation to remain in the nasal cavity long enough to release a therapeutic dose.
To meet this need, the researchers formulated a two-component supramolecular hydrogel based on an l-glutamine amide derivative combined with benzaldehyde. This self-healing gel encapsulates levodopa and has soft rheological properties suitable for flow during application and rapid gelation inside the nose. Laboratory testing confirmed the gel releases levodopa rapidly from its network while remaining compatible with nasal epithelial cells.
In collaboration with a team at King’s College London, the gel was evaluated in animal models. The studies used radiolabeled l‑DOPA to track distribution and showed that intranasal administration of the levodopa-loaded gel delivered higher concentrations of drug to both the blood and the brain than an equivalent intranasal solution. In some comparisons, brain uptake from the nasal gel exceeded uptake following intravenous injection of the drug, suggesting the nasal route with this gel can improve brain delivery efficiency.
Professor Smith commented that the gel improved adhesion within the nasal cavity, increasing residence time and enabling greater uptake into the bloodstream and brain. The research team is now adapting the material for use in nasal spray devices with the aim of progressing to clinical trials in humans. They note the approach could also have relevance for delivery of drugs targeting other neurodegenerative conditions such as Alzheimer’s disease.
Khuloud Al-Jamal, Professor of Drug Delivery and Nanomedicine at King’s College London, highlighted that the gel outperformed a simple drug solution in the nasal cavity and produced superior brain uptake compared with intravenous administration. These findings support the potential clinical relevance of nasal gel delivery for Parkinson’s medications.
Funding: This research was conducted as part of the Centre for Future Health and supported by The Wellcome Trust. The results are published in the journal Advanced Science.
About this Parkinson’s disease research news
Source: University of York
Contact: Julie Gatenby – University of York
Image: The image is in the public domain
Original Research: Open access.
“Enhanced Delivery of Neuroactive Drugs via Nasal Delivery with a Self-Healing Supramolecular Gel” by David Smith et al. Advanced Science
Abstract
Enhanced Delivery of Neuroactive Drugs via Nasal Delivery with a Self-Healing Supramolecular Gel
The published study describes a self-assembling hydrogel used to deliver l‑DOPA via the nasal route. Constructed from an l‑glutamine amide derivative and benzaldehyde, the material forms a soft, self-healing gel capable of encapsulating levodopa. The gel’s rheological profile allows it to flow for administration and then form a stable layer that prolongs residence time in the nasal cavity.
Characterization of the drug-loaded gels showed rapid drug release from the network and mechanical properties compatible with administration. In vitro assessments demonstrated biocompatibility with nasal epithelial cells, supporting the formulation’s suitability for intranasal use.
Animal studies comparing intranasal gel with a simple intranasal solution indicated superior performance for the gel, producing increased blood and brain concentrations of radiolabeled l‑DOPA. The enhanced delivery is attributed to prolonged nasal residence, enabling uptake along neural pathways, including the trigeminal and olfactory nerves, which connect the nasal cavity to various brain regions.
Taken together, these findings suggest that a self-healing supramolecular nasal gel can enhance delivery of neuroactive drugs to the brain, offering a potential strategy to improve treatment of Parkinson’s disease and possibly other neurological disorders while reducing reliance on higher systemic doses.