Summary: A new gel that contains levodopa can adhere to nasal tissue. The gel releases levodopa directly into the blood and brain. Researchers say the preliminary data reveals the gel has proven to be effective in animal models.
Source: University of York
Scientists at the University of York have made significant progress in the development of a nasal spray treatment for patients with Parkinson’s disease.
Researchers have developed a new gel that can adhere to tissue inside the nose alongside the drug levodopa, helping deliver treatment directly to the brain.
Levodopa is converted to dopamine in the brain, which makes-up for the deficit of dopamine-producing cells in Parkinson’s patients, and helps treat the symptoms of the disease. Over extended periods of time, however, levodopa becomes less effective, and increased doses are needed.
Professor David Smith, from the University of York’s Department of Chemistry, said: “The current drug used for Parkinson’s Disease is effective to a point, but after a long period of use the body starts to breakdown the drug before it gets to the brain where it is most needed.
“This means increased dosage is necessary, and in later stages, sometimes, instead of tablets, the drug has to be injected. Investigations into nasal sprays have long been of interest as a more effective delivery because of its direct route to the brain via the nerves that service the nose, but the challenge here is to find a way of making it adhere to the nasal tissue long enough to release a good dosage of the drug.”
The researchers created a gel, loaded with levodopa, that could flow into the nose as a liquid and then rapidly change to a thin layer of gel inside the nose. The method was tested in animal models by a team at King’s College London, where levodopa was successfully released from the gel into the blood and directly to the brain.
Professor Smith said: “The results indicated that the gel gave the drug better adhesion inside the nose, which allowed for better levels of uptake into both the blood and brain.”
The team are now working to incorporate these materials in nasal spray devices to progress to clinical trials in humans. The approach may also be relevant to other neurodegenerative diseases such as Alzheimer’s.
Khuloud Al-Jamal, Professor of Drug Delivery and Nanomedicine from King’s College London, said: “Not only did the gel perform better than a simple solution, but the brain uptake was better than that achieved using intravenous injection of the drug. This suggests that nasal delivery of Parkinson’s drugs using this type of gel may have clinical relevance.”
Funding: The research, part of the Centre for Future Health, and funded by The Wellcome Trust, is 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
Enhanced Delivery of Neuroactive Drugs via Nasal Delivery with a Self-Healing Supramolecular Gel
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.