New formulation of ibudilast found to ease inflammation in MS mice

A novel formulation of ibudilast, delivered into the nose, was able to reduce inflammation and prevent nerve damage in a mouse model of multiple sclerosis (MS), a study found.

The nasal formulation also improved regeneration of myelin, the protective sheath around nerve fibers that is progressively lost in MS.

According to researchers, this new formulation holds promise as an easier and better way to administer the therapy.

“Intranasal administration can offer a non-invasive method to directly deliver ibudilast to the brain for the treatment of MS,” the team wrote.

The study, “Nose to brain delivery of ibudilast micelles for treatment of multiple sclerosis in an experimental autoimmune encephalomyelitis animal model,” was published in the International Journal of Pharmaceutics. The work was funded by Raha Pharmaceutical, an Iranian-based company that counts 15 nasal sprays among its 130 products.

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Testing the new formulation in a mouse model of MS

In multiple sclerosis, inflammation in the brain and spinal cord damages the myelin sheath, a fatty covering around nerve fibers that helps them send electrical signals. Damage to myelin leads to problems with these electrical signals, and the resulting neurological dysfunction ultimately is what causes symptoms of MS.

Ibudilast is a small molecule with anti-inflammatory properties. MediciNova is developing an oral formulation of the molecule  — known as MN-166 — as a potential treatment for MS.

Early clinical trial data suggested that the oral therapy could slow the rate of brain atrophy (shrinkage) in people with progressive types of MS. However, the data did not show any effect on life quality for treated patients, and digestive side effects like nausea, diarrhea, abdominal pain, and vomiting were common.

Now, a team of scientists in Iran set out to create a version of ibudilast that could be administered through the nose directly into the brain. This route of administration promises to maximize efficacy by getting the medication directly where it’s needed, they said.

Moreover, it also might minimize side effects by avoiding putting the medication into the digestive system.

To create their intranasal or into-the-nose formulation, the scientists manufactured ibudilast micelles — essentially, tiny molecular bubbles containing the therapy.

These molecular bubbles were then coated with polydopamine (PDA), a molecule with a similar structure to dopamine, which is a chemical used by nerve cells to signal to each other. That coating aimed to facilitate better uptake of the medication by cells in the nervous system.

The scientists tested three daily doses — 10, 25, and 50 mg per kg of body weight — of their novel formulation in mice with experimental autoimmune encephalomyelitis, a common mouse model of MS.

Results showed that mice treated with the higher doses of the micelle ibudilast formulation had significantly less myelin damage compared with untreated mice.

This suggested that “the dose of 25 and 50 mg/kg/day of nasal [ibudilast] can increase re-myelination in MS,” the scientists wrote.

These findings suggest the benefit of intranasal delivery of ibudilast … in active MS.

Data also showed that this ibudilast formulation led to decreases in levels of inflammatory immune cells and signaling molecules, while simultaneously increasing the activity of myelin-making cells in the brain.

However, neither oral ibudilast nor administering the therapy through the nose but without the molecular bubble formulation exerted these same myelin-protecting and anti-inflammatory effects. Data suggested that the novel formulation led to higher levels of the active medication in brain tissue.

“These findings suggest the benefit of intranasal delivery of ibudilast by PDA coated surfactin micelles in active MS,” the scientists concluded.