Gel formulation of neuroactive drugs for Parkinson’s disease that is administered intranasally may be a more effective method of administration

Nasal delivery of neuroactive drugs for Parkinson’s disease (PD) in a gel formulation included the trigeminal and olfactory nerves and elevated blood and brain concentrations. These results were published in Advanced Science.

In vitro and in vivo studies were carried out using human cell, mouse and rat models. All assays were performed at King’s College London.

The gel formulation comprised glutamine amide derivative (3.5 mg) and benzaldehyde (1.15 mg) mixed with 3.5 mg of 1-3,4-dihydroxyphenylalanine (L-DOPA) and 1 ml of water.

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On proton nuclear magnetic resonance, 92% of the L-DOPA was visible in the gel formulation.

During the in vitro assays, the gel was exposed to a pH 7 supernatant. The study researchers observed a rapid release of L-DOPA and that the active ingredient did not interact with the solid-like gel nanofibers, but within the liquid-like components.

The gel formulation was exposed to human nasal epithelial cells. L-DOPA (4.8 x 10 -3 M) was incubated in 1%, 2%, 5% and 10% (v / v) gels for 24 and 48 hours. With the exception of the highest concentration at the longest exposure time, no toxicity events were observed.

Mice were exposed to the L-DOPA gel and a simple L-DOPA solution. The gel formulation was more effective (0.49% ± 0.32% ID) compared to a simple solution formulation (0.16% ± 0.08% ID) after 10 minutes (0.01).

After 10 minutes, 27.55% ± 3.73% ID of L-DOPA remained in the nasal cavity and after 20 minutes, 15.70% ± 4.7% ID.

In the liver of mice that received the gel formulation, L-DOPA was at a lower concentration than the simple solution (0.01

Hemiparkinsonian model rats given an intranasal dose of 0.35 mg / kg-1 of L-DOPA demonstrated effective foreleg placement after 30 minutes.

L-DOPA was found to be distributed throughout the brain, with the highest concentrations in the trigeminal nerves. The drug was transported to the brain directly through the trigeminal and olfactory nerves, which come from the cerebrum and brain stem pons.

It remains unclear to what extent these results can be transferred to patients with PD.

These data indicated that a gel formulation of neuroactive drugs administered through the nasal cavity could be a superior method of delivery for patients with Parkinson’s disease.

reference

Tzu-Wen Wang J, Rodrigo AC, Patterson AK et al. Improved delivery of neuroactive drugs through nasal delivery with a self-healing supramolecular gel. Adult Sci. Published online May 24, 2021. doi: 10.1002 / advs.202101058

This article originally appeared on Psychiatry Advisor