Gel Formulation of Neuroactive Drugs for Parkinson Disease Administered Intranasally May Be More Effective Delivery Method

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The study researchers reported on a self-assembled hydrogel to deliver the drug 4-dihydroxyphenylalanine (L-DOPA) for Parkinson disease.

Nasal delivery of neuroactive drugs for Parkinson disease (PD) in a gel formulation involved the trigeminal and olfactory nerves and increased blood and brain concentrations. These findings were published in Advanced Science.

In vitro and in vivo studies were performed 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 l-3, 4-dihydroxyphenylalanine (L-DOPA) and 1 mL of water.

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

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

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

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 with a simple solution formulation (0.16%±0.08% ID) at 10 minutes (0.01<P<.05).

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

Within the liver, L-DOPA was at a lower concentration at 20 minutes among mice who received the gel formulation compared with the simple solution (0.01<P<.05). L-DOPA was at higher concentrations in the brain (0.49%±0.32% vs 0.12%±0.01% ID) and blood (0.79%±0.11% vs 0.37%±0.24% ID; P <.01) with the gel formulation.

Hemiparkinsonian model rats that received a 0.35 mg/kg−1intranasal dose of L-DOPA exhibited effective forelimb placing at 30 minutes.

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

It remains unclear to which extent these findings may be translated to patients with PD.

These data indicated a gel formulation of neuroactive drugs delivered through the nasal cavity may be a superior delivery method for patients with PD.


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